Appendices for U.S. Medical Eligibility Criteria for Contraceptive Use, 2016

View associated article

Appendix A

Summary of Changes from U.S. Medical Eligibility Criteria for Contraceptive Use, 2010

The classification additions, deletions, and modifications from the 2010 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) are summarized in the following tables ( Box A1) ( Tables A1 and A2). For conditions for which classifications changed for one or more contraceptive methods or the condition description underwent a major modification, the changes or modifications are in bold italics (Tables A1 and A2). Conditions that do not appear in this table remain unchanged from the 2010 U.S. MEC.

Return to your place in the textBOX A1. Categories for classifying intrauterine devices and hormonal contraceptives

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE A1. Summary of changes in classifications from U.S. Medical Eligibility Criteria for Contraceptive Use, 2010*
Condition Cu-IUD LNG-IUD Implants DMPA POP CHCs Clarification
Breastfeeding
a. <21 days postpartum 2 2 2 4 Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
b. 21 to <30 days postpartum
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 2 2 2 3 Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
CHCs: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
   ii. Without other risk factors for VTE 2 2 2 3 Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
c. 30–42 days postpartum
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 1 1 1 3 Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
CHCs: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
   ii. Without other risk factors for VTE
1 1 1 2 Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
d. >42 days postpartum 1 1 1 2 Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
Postpartum (nonbreastfeeding women)
a. <21 days postpartum 1 1 1 4
b. 21–42 days postpartum
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 1 1 1 3 CHCs: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
   ii. Without other risk factors for VTE 1 1 1 2
c. >42 days postpartum 1 1 1 1
Postpartum (including cesarean delivery)
a. <10 minutes after delivery of the placenta IUDs: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
Breastfeeding: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (
1).
   i. Breastfeeding 1 2
   ii. Nonbreastfeeding 1 1
b. 10 minutes after delivery of the placenta to <4 weeks (breastfeeding or nonbreastfeeding) 2 2 IUDs: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
Breastfeeding: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
c. =4 weeks (breastfeeding or nonbreastfeeding) 1 1 IUDs: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
Breastfeeding: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (1).
d. Postpartum sepsis 4 4
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels) 1 2 2 3 2 3/4 Implants, DMPA, POP: When multiple major risk factors exist, risk for cardiovascular disease might increase substantially. Certain POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs. The effects of DMPA might persist for some time after discontinuation.
CHCs: When a woman has multiple major risk factors, any of which alone would substantially increase her risk for cardiovascular disease, use of CHCs might increase her risk to an unacceptable level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two category 2 risk factors might not necessarily warrant a higher category.
Implants, DMPA, POP, CHCs: The recommendations apply to known preexisting medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See the U.S. Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usspr.htm)
Superficial venous disorders
a. Varicose veins 1 1 1 1 1 1
b. Superficial venous thrombosis (acute or history) 1 1 1 1 1 3 CHCs: Superficial venous thrombosis might be associated with an increased risk for VTE. If a woman has risk factors for concurrent DVT (e.g., known thrombophilia or cancer) or has current or history of DVT, see recommendations for DVT/PE. Superficial venous thrombosis associated with a peripheral intravenous catheter is less likely to be associated with additional thrombosis and use of CHCs may be considered.
Headaches
a. Nonmigraine (mild or severe) 1 1 1 1 1 1 CHCs: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf). Any new headaches or marked changes in headaches should be evaluated.
b. Migraine CHCs: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf). Any new headaches or marked changes in headaches should be evaluated.
CHCs: Classification is for women without any other risk factors for stroke (e.g., age, hypertension, and smoking).
   i. Without aura (This category of migraine includes menstrual migraine.) 1 1 1 1 1 2
   ii. With aura 1 1 1 1 1 4
Multiple sclerosis
a. With prolonged immobility 1 1 1 2 1 3
b. Without prolonged immobility 1 1 1 2 1 1
Gestational trophoblastic disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
a. Suspected gestational trophoblastic disease (immediate postevacuation) For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
   i. Uterine size first trimester 1 1 1 1 1 1
   ii. Uterine size second trimester 2 2 1 1 1 1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring) Initiation Continuation Initiation Continuation
   i. Undetectable/nonpregnant ß-hCG levels 1 1 1 1 1 1 1 1 For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
   ii. Decreasing ß-hCG levels 2 1 2 1 1 1 1 1 For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
IUD: For women at higher risk for disease progression, the benefits of effective contraception must be weighed against the potential need for early IUD removal.
   iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease 2 1 2 1 1 1 1 1 For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
   iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease 4 2 4 2 1 1 1 1 For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Sexually transmitted diseases Initiation Continuation Initiation Continuation
a. Current purulent cervicitis or chlamydial infection or gonococcal infection 4 2 4 2 1 1 1 1 IUD continuation: Treat the STD using appropriate antibiotics. The IUD usually does not need to be removed if the woman wants to continue using it. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STDs and PID.
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) 2 2 2 2 1 1 1 1
c. Other factors related to STDs 2 2 2 2 1 1 1 1 IUD initiation: Most women do not require additional STD screening at the time of IUD insertion. If a woman with risk factors for STDs has not been screened for gonorrhea and chlamydia according to CDC STD treatment guidelines (2), screening may be performed at the time of IUD insertion and insertion should not be delayed.
High risk for HIV Initiation Continuation Initiation Continuation DMPA: Some studies suggest that women using progestin-only injectable contraception might be at increased risk for HIV acquisition; other studies do not show this association. CDC reviewed all available evidence and agreed that the data were not sufficiently conclusive to change current guidance. However, because of the inconclusive nature of the body of evidence on possible increased risk for HIV acquisition, women using progestin-only injectable contraception should be strongly advised to also always use condoms (male or female) and take other HIV preventive measures. Expansion of contraceptive method mix and further research on the relationship between hormonal contraception and HIV infection are essential. These recommendations will be continually reviewed in light of new evidence.
2 2 2 2 1 1 1 1
HIV infection
For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 1 Implants, DMPA, POP, CHCs: Drug interactions might exist between hormonal contraceptives and ARV drugs; see Drug Interactions section.
a. Clinically well receiving ARV therapy 1 1 1 1
b. Not clinically well or not receiving ARV therapy 2 1 2 1
Cystic fibrosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 2 1 1 Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
Implants, DMPA, POP, CHCs: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives.
Antiretroviral therapy Initiation Continuation Initiation Continuation IUD: No known interaction exists between ARV therapy and IUD use. However, IUD insertion is classified as category 2 if the woman is not clinically well or not receiving ARV therapy. Otherwise, both insertion and continuation are classified as category 1 (see HIV Infection section).
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
   i. Abacavir (ABC) 1/2 1 1/2 1 1 1 1 1
   ii. Tenofovir (TDF) 1/2 1 1/2 1 1 1 1 1
   iii. Zidovudine (AZT) 1/2 1 1/2 1 1 1 1 1
   iv. Lamivudine (3TC) 1/2 1 1/2 1 1 1 1 1
   v. Didanosine (DDI) 1/2 1 1/2 1 1 1 1 1
   vi. Emtricitabine (FTC) 1/2 1 1/2 1 1 1 1 1
   vii. Stavudine (D4T) 1/2 1 1/2 1 1 1 1 1
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
   i. Efavirenz (EFV) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP, CHCs: Evidence suggests drug interactions between efavirenz and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
   ii. Etravirine (ETR) 1/2 1 1/2 1 1 1 1 1
   iii. Nevirapine (NVP) 1/2 1 1/2 1 1 1 1 1
   iv. Rilpivirine (RPV) 1/2 1 1/2 1 1 1 1 1
c. Ritonavir-boosted protease inhibitors
   i. Ritonavir-boosted atazanavir (ATV/r) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
   ii. Ritonavir-boosted darunavir (DRV/r) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
   iii. Ritonavir-boosted fosamprenavir (FPV/r) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
   iv. Ritonavir-boosted lopinavir (LPV/r) 1/2 1 1/2 1 1 1 1 1
   v. Ritonavir-boosted saquinavir (SQV/r) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
   vi. Ritonavir-boosted tipranavir (TPV/r) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
CHCs: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
d. Protease inhibitors without ritonavir
   i. Atazanavir (ATV) 1/2 1 1/2 1 1 1 1 2 CHCs: Theoretical concern exists that increased levels of ethinyl estradiol because of interactions with ATV might increase the risk for adverse events.
   ii. Fosamprenavir (FPV) 1/2 1 1/2 1 2 2 2 3 Implants, DMPA, POP: Theoretical concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the antiretroviral drug. The drug interaction likely involves CYP3A4 pathways; POCs have less effect on CYP3A4 enzymes than CHCs.
CHCs: Concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the antiretroviral drug.
   iii. Indinavir (IDV) 1/2 1 1/2 1 1 1 1 1
   iv. Nelfinavir (NFV) 1/2 1 1/2 1 2 1 2 2 Implants, DMPA, POP: Theoretically, drug interactions might occur between certain protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA. Concern exists that interactions between NFV and POCs might decrease NFV levels.
CHCs: Evidence suggests drug interactions between certain protease inhibitors and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
e. CCR5 co-receptor antagonists
   i. Maraviroc (MVC) 1/2 1 1/2 1 1 1 1 1
f. HIV integrase strand transfer inhibitors
   i. Raltegravir (RAL) 1/2 1 1/2 1 1 1 1 1
   ii. Dolutegravir (DTG) 1/2 1 1/2 1 1 1 1 1
   iii. Elvitegravir (EVG) 1/2 1 1/2 1 1 1 1 1
g. Fusion inhibitors
   i. Enfuvirtide 1/2 1 1/2 1 1 1 1 1
Psychotropic medications
a. SSRIs 1 1 1 1 1 1
St. John’s wort 1 1 2 1 2 2

Abbreviations: ARV = antiretroviral; BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined oral contraceptive; Cu-IUD = copper-containing intrauterine device; DMPA = depot medroxyprogesterone acetate; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; LDL = low-density lipoprotein; LNG-IUD = levonorgestrel-releasing intrauterine device; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; POP = progestin-only pill; SSRI = selective serotonin uptake inhibitor; STD = sexually transmitted disease; VTE = venous thromboembolism.

* For conditions for which classification changed for one or more contraceptive methods or the condition description underwent a major modification, the changes or modifications are in bold italics.

Return to your place in the textTABLE A2. Summary of changes for emergency contraception from U.S. Medical Eligibility Criteria for Contraceptive Use, 2010*
Condition Category Clarification
Cu-IUD UPA LNG COC
Pregnancy 4 NA NA NA IUD: The IUD is not indicated during pregnancy and should not be used because of the risk for serious pelvic infection and septic spontaneous abortion.
ECPs: Although this method is not indicated for a woman with a known or suspected pregnancy, no harm to the woman, the course of her pregnancy, or the fetus if ECPs are inadvertently used is known to exist.
Breastfeeding 1 1 1 1 UPA: Breastfeeding is not recommended for 24 hours after taking UPA because it is excreted in breast milk with highest concentrations in the first 24 hours, and maximum maternal serum levels are reached 1-3 hours after administration. Mean UPA concentrations in breast milk decrease markedly from 0 to 24–48 hours and then slowly decrease over 5 days (3). Breast milk should be expressed and discarded for 24 hours after taking UPA.
Past ectopic pregnancy 1 1 1 1
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 1 1 1
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) 1 1 1 1
History of severe cardiovascular disease (ischemic heart disease, cerebrovascular attack, or other thromboembolic conditions)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 2 2
Rheumatoid arthritis
a. Receiving immunosuppressive therapy 2 1 1 1
b. Not receiving immunosuppressive therapy 1 1 1 1
Migraine 1 1 1 2
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease) 1 1 1 1
Severe liver disease (including jaundice)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 2 2
Solid organ transplantation
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy 3 1 1 1
b. Uncomplicated 2 1 1 1
Repeated ECP use 1 1 1 1 ECPs: Recurrent ECP use is an indication that the woman requires further counseling about other contraceptive options. Frequently repeated ECP use might be harmful for women with conditions classified as 2, 3, or 4 for CHC or POC use.
Sexual assault 2 1 1 1 IUD: Women who have experienced sexual assault are at increased risk for STDs. According to CDC STD treatment guidelines, routine presumptive treatment of chlamydia, gonorrhea, and trichomonas is recommended after sexual assault (2). Women with current purulent cervicitis or chlamydial infection or gonococcal infection should not undergo IUD insertion (category 4).
Obesity (BMI =30 kg/m2) 1 2 2 2 ECPs: ECPs might be less effective among women with BMI =30 kg/m2 than among women with BMI <25 kg/m2. Despite this, no safety concerns exist.
CYP3A4 inducers (e.g., bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John’s wort, topiramate, efavirenz, and lumacaftor) 1 2 2 2 ECPs: Strong CYP3A4 inducers might reduce the effectiveness of ECPs.

Abbreviations: BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined oral contraceptive; Cu-IUD = copper-containing intrauterine device; ECP = emergency contraceptive pill; IUD = intrauterine device; LNG = levonorgestrel; NA = not applicable; POC = progestin-only contraceptive; STD = sexually transmitted disease; UPA = ulipristal acetate.

* For conditions for which classification changed for one or more contraceptive methods or the condition description underwent a major modification, the changes or modifications are in bold italics.

References

  1. US Department of Health and Human Services. Healthy people 2020: maternal, infant, and child health objectives. Washington, DC: US Department of Health and Human Services; 2015. http://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health/objectives
  2. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-03). PubMed
  3. Watson Pharmaceuticals. Ella [Prescribing information]. Morristown, NJ; 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022474s000lbl.pdf

Appendix B

Classifications for Intrauterine Devices

Classifications for intrauterine devices (IUDs) are for the copper-containing IUD and levonorgestrel-releasing IUD (containing a total of either 13.5 mg or 52 mg levonorgestrel) ( Box B1) ( Table B1). IUDs do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Return to your place in the textBOX B1. Categories for classifying intrauterine devices

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE B1. Classifications for intrauterine devices, including the copper-containing intrauterine device and levonorgestrel-releasing intrauterine device
Condition Category Clarifications/Evidence/Comments
Cu-IUD LNG-IUD
Personal Characteristics and Reproductive History
Pregnancy 4 4 Clarification: The IUD is not indicated during pregnancy and should not be used because of the risk for serious pelvic infection and septic spontaneous abortion.
Age
a. Menarche to <20 years 2 2 Comment: Concern exists both about the risk for expulsion from nulliparity and for STDs from sexual behavior in younger age groups.
b. =20 years 1 1
Parity
a. Nulliparous 2 2 Evidence: Data conflict about whether IUD use is associated with infertility among nulliparous women, although well-conducted studies suggest no increased risk (19).
b. Parous 1 1
Postpartum (including cesarean delivery)
a. <10 minutes after delivery of the placenta Clarification: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
Clarification (breastfeeding): Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10).
Evidence: Studies suggest that immediate postplacental (<10 minutes) and early postpartum (10 minutes up until 72 hours) placement of Cu-IUDs and LNG-IUDs is associated with increased risk for expulsion compared with interval placement (i.e., not related to pregnancy). Early postpartum placement has similar or increased risk for expulsion compared with immediate postplacental placement. Although immediate postplacental placement at the time of cesarean delivery might have increased risk for expulsion compared with interval placement, risk appears lower than that for placement at the time of vaginal delivery. Evidence for infection, perforation, and removals for pain or bleeding are limited; however, these events are rare (1162).
Evidence (breastfeeding): Two randomized controlled trials found conflicting results on breastfeeding outcomes when LNG-IUDs were initiated immediately postpartum compared with 6–8 weeks postpartum. Initiation of LNG-IUDs immediately postpartum had no other harmful effect on infant health, growth, or development (63,64). Breastfeeding women using IUDs do not have an increased risk for certain IUD-related adverse events including expulsion, infection, pain, or bleeding compared with nonbreastfeeding women. The risk for perforation is increased independently among breastfeeding women and among women =36 weeks postpartum, compared with non-postpartum women; however, the absolute risk for perforation remains low (1162,65).
Comment (breastfeeding): Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
   i. Breastfeeding 1 2
   ii. Nonbreastfeeding 1 1
b. 10 minutes after delivery of the placenta to <4 weeks (breastfeeding or nonbreastfeeding) 2 2 Clarification: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
Clarification (breastfeeding): Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10).
Evidence: Studies suggest that immediate postplacental (<10 minutes) and early postpartum (10 minutes up until 72 hours) placement of Cu-IUDs and LNG-IUDs is associated with increased risk for expulsion compared with interval placement (i.e., not related to pregnancy). Early postpartum placement has similar or increased risk for expulsion compared with immediate postplacental placement. Although immediate postplacental placement at the time of cesarean delivery might have increased risk for expulsion compared with interval placement, risk appears lower than that for placement at the time of vaginal delivery. Evidence for infection, perforation, and removals for pain or bleeding are limited; however, these events are rare (1162).
Evidence (breastfeeding): Two randomized controlled trials found conflicting results on breastfeeding outcomes when LNG-IUDs were initiated immediately postpartum compared with 6–8 weeks postpartum. Initiation of LNG-IUDs immediately postpartum had no other harmful effect on infant health, growth, or development (63,64). Breastfeeding women using IUDs do not have an increased risk for certain IUD-related adverse events including expulsion, infection, pain, or bleeding compared with nonbreastfeeding women. The risk for perforation is increased independently among breastfeeding women and among women =36 weeks postpartum, compared with non-postpartum women; however, the absolute risk for perforation remains low (1162,65).
Comment (breastfeeding): Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
c. =4 weeks (breastfeeding or nonbreastfeeding) 1 1 Clarification: Insertion of IUDs among postpartum women is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness, along with patient access to interval placement (i.e., not related to pregnancy) when expulsion rates are lower.
Clarification (breastfeeding): Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (10).
Evidence (breastfeeding): Initiation of LNG-IUDs at 4 weeks postpartum or later demonstrated no detrimental effect on breastfeeding outcomes and no harmful effect on infant health, growth, or development (63,64). Breastfeeding women using IUDs do not have an increased risk for certain IUD-related adverse events including expulsion, infection, pain, or bleeding compared with nonbreastfeeding women. The risk for perforation is increased independently among breastfeeding women and among women =36 weeks postpartum, compared with non-postpartum women; however, the absolute risk for perforation remains low (1162,65).
Comment (breastfeeding): Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
d. Postpartum sepsis 4 4 Comment: Theoretical concern exists that postpartum insertion of an IUD in a women with recent chorioamnionitis or current endometritis might be associated with increased complications.
Postabortion
a. First trimester 1 1 Clarification: IUDs can be inserted immediately after spontaneous or induced abortion.
Evidence: Risk for complications from immediate versus delayed insertion of an IUD after abortion did not differ. Expulsion was greater when an IUD was inserted after a second trimester abortion than when inserted after a first trimester abortion. Safety or expulsion for postabortion insertion of an LNG-IUD did not differ from that of a Cu-IUD (66).
b. Second trimester 2 2
c. Immediate postseptic abortion 4 4 Comment: Insertion of an IUD might substantially worsen the condition.
Past ectopic pregnancy 1 1 Comment: The absolute risk for ectopic pregnancy is extremely low because of the high effectiveness of IUDs. However, when a woman becomes pregnant during IUD use, the relative likelihood of ectopic pregnancy increases substantially.
History of pelvic surgery
(see Postpartum [Including Cesarean Delivery] section)
1 1
Smoking
a. Age <35 years 1 1
b. Age =35 years
   i. <15 cigarettes per day 1 1
   ii. =15 cigarettes per day 1 1
Obesity
a. BMI =30 kg/m2 1 1
b. Menarche to <18 years and BMI =30 kg/m2 1 1
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 1
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) 1 1
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels) 1 2
Hypertension
Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension 1 1 Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
b. Elevated blood pressure levels
(properly taken measurements)
Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
   i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg 1 1
   ii. Systolic =160 mm Hg or diastolic =100 mm Hg 1 2
c. Vascular disease 1 2 Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal) 1 1
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
   i. Higher risk for recurrent DVT/PE (one or more risk factors) 1 2
      • History of estrogen-associated DVT/PE
• Pregnancy-associated DVT/PE
• Idiopathic DVT/PE
• Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
   ii. Lower risk for recurrent DVT/PE (no risk factors) 1 2
b. Acute DVT/PE 2 2 Evidence: No direct evidence exists on the use of POCs among women with acute DVT/PE. Although findings on the risk for venous thrombosis with the use of POCs in otherwise healthy women are inconsistent, any small increased risk is substantially less than that with COCs (6769).
c. DVT/PE and established anticoagulant therapy for at least 3 months Evidence: No direct evidence exists on the use of POCs among women with acute DVT/PE. Although findings on the risk for venous thrombosis with the use of POCs in otherwise healthy women are inconsistent, any small increased risk is substantially less than that with COCs (6769).
Evidence: Limited evidence indicates that insertion of the LNG-IUD does not pose major bleeding risks in women receiving chronic anticoagulant therapy (7073).
Comment: The LNG-IUD might be a useful treatment for menorrhagia in women receiving long-term anticoagulation therapy.
   i. Higher risk for recurrent DVT/PE (one or more risk factors) 2 2
      • Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
   ii. Lower risk for recurrent DVT/PE (no risk factors) 2 2
d. Family history (first-degree relatives) 1 1
e. Major surgery
   i. With prolonged immobilization 1 2
   ii. Without prolonged immobilization 1 1
f. Minor surgery without immobilization 1 1
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; and protein S, protein C, and antithrombin deficiencies)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
Superficial venous disorders
a. Varicose veins 1 1
b. Superficial venous thrombosis (acute or history) 1 1
Current and history of ischemic heart disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 Initiation Continuation Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
2 3
Stroke (history of cerebrovascular accident)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 Comment: Theoretical concern exists about the effect of LNG on lipids. Use of Cu-IUDs has no restrictions.
Valvular heart disease
Complicated valvular heart disease is a condition associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Comment: According to the American Heart Association, administration of prophylactic antibiotics solely to prevent endocarditis is not recommended for patients who undergo genitourinary tract procedures, including insertion or removal of IUDs (74).
a. Uncomplicated 1 1
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis) 1 1
Peripartum cardiomyopathy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Evidence: No direct evidence exists on the safety of IUDs among women with peripartum cardiomyopathy. Limited indirect evidence from noncomparative studies did not demonstrate any cases of arrhythmia or infective endocarditis in women with cardiac disease who used IUDs (75).
Comment: IUD insertion might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (76)
   i. <6 months 2 2
   ii. =6 months 2 2
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (76) 2 2
Rheumatic Diseases
Systemic lupus erythematosus
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation
a. Positive (or unknown) antiphospholipid antibodies 1 1 3 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,7794).
Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (95,96).
b. Severe thrombocytopenia 3 2 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,7794).
Clarification: Severe thrombocytopenia increases the risk for bleeding. The category should be assessed according to the severity of thrombocytopenia and its clinical manifestations. In women with very severe thrombocytopenia who are at risk for spontaneous bleeding, consultation with a specialist and certain pretreatments might be warranted.
Evidence: The LNG-IUD might be a useful treatment for menorrhagia in women with severe thrombocytopenia (73).
c. Immunosuppressive therapy 2 1 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,7794).
d. None of the above 1 1 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (73,7794).
Rheumatoid arthritis Initiation Continuation Initiation Continuation
a. Receiving immunosuppressive therapy 2 1 2 1
b. Not receiving immunosuppressive therapy 1 1
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe) 1 1
b. Migraine
   i. Without aura (This category of migraine includes menstrual migraine.) 1 1 Evidence: No studies directly examined the risk for stroke among women with migraine using LNG-IUDs (97). Limited evidence demonstrated that women using LNG-IUDs do not have an increased risk for ischemic stroke compared with women not using hormonal contraceptives (98).
Comment: Menstrual migraine is a subtype of migraine without aura. For more information see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf).
   ii. With aura 1 1
Epilepsy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1
Multiple sclerosis
a. With prolonged immobility 1 1
b. Without prolonged immobility 1 1
Depressive Disorders
Depressive disorders 1 1 Clarification: If a woman is receiving psychotropic medications or St. John’s wort, see Drug Interactions section.
Evidence: The frequency of psychiatric hospitalizations for women with bipolar disorder or depression did not significantly differ among women using DMPA, LNG-IUD, Cu-IUD, or sterilization (99).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns Initiation Continuation
a. Irregular pattern without heavy bleeding 1 1 1
b. Heavy or prolonged bleeding (includes regular and irregular patterns) 2 1 2 Clarification: Unusually heavy bleeding should raise suspicion of a serious underlying condition.
Evidence: Evidence from studies examining the treatment effects of the LNG-IUD among women with heavy or prolonged bleeding reported no increase in adverse effects and found the LNG-IUD to be beneficial in treating menorrhagia (100107).
Unexplained vaginal bleeding
(suspicious for serious condition) before evaluation
Initiation
4
Continuation
2
Initiation
4
Continuation
2
Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. The IUD does not need to be removed before evaluation.
Endometriosis 2 1 Evidence: LNG-IUD use among women with endometriosis decreased dysmenorrhea, pelvic pain, and dyspareunia (108112).
Benign ovarian tumors (including cysts) 1 1
Severe dysmenorrhea 2 1 Comment: Dysmenorrhea might intensify with Cu-IUD use. LNG-IUD use has been associated with reduction of dysmenorrhea.
Gestational trophoblastic disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Suspected gestational trophoblastic disease (immediate postevacuation) Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
Comment: The risk for expulsion immediately postevacuation for gestational trophoblastic disease is unknown. Expulsion is greater after IUD insertion immediately postevacuation for a spontaneous or induced abortion in the second trimester compared with IUD insertion after a first trimester abortion.
   i. Uterine size first trimester 1 1
   ii. Uterine size second trimester 2 2
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring) Initiation Continuation Initiation Continuation
   i. Undetectable/nonpregnant ß-hCG levels 1 1 1 1 Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
Comment: Once ß-hCG levels have decreased to nonpregnant levels, the risk for disease progression is likely to be very low.
   ii. Decreasing ß-hCG levels 2 1 2 1 Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Clarification: For women at higher risk for disease progression, the benefits of effective contraception must be weighed against the potential need for early IUD removal.
Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
   iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease 2 1 2 1 Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
   iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease 4 2 4 2 Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Evidence: Limited evidence suggests that women using an IUD after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (113).
Comment: For women with suspected or confirmed intrauterine disease, an IUD should not be inserted because of theoretical risk for perforation, infection, and hemorrhage. For women who already have an IUD in place, individual circumstance along with the benefits of effective contraception must be weighed against theoretical risks of either removal or continuation of the IUD.
Cervical ectropion 1 1
Cervical intraepithelial neoplasia 1 2 Comment: Theoretical concern exists that LNG-IUDs might enhance progression of cervical intraepithelial neoplasia.
Cervical cancer (awaiting treatment) Initiation Continuation Initiation Continuation Comment: Concern exists about the increased risk for infection and bleeding at insertion. The IUD most likely will need to be removed at the time of treatment but until then, the woman is at risk for pregnancy.
4 2 4 2
Breast disease
Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass 1 2
b. Benign breast disease 1 1
c. Family history of cancer 1 1
d. Breast cancer Comment: Breast cancer is a hormonally sensitive tumor. Concerns about progression of the disease might be less with LNG-IUDs than with COCs or higher-dose POCs.
   i. Current 1 4
   ii. Past and no evidence of current disease for 5 years 1 3
Endometrial hyperplasia 1 1 Evidence: Among women with endometrial hyperplasia, no adverse health events occurred with LNG-IUD use; most women experienced disease regression (114).
Endometrial cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation Initiation Continuation Comment: Concern exists about the increased risk for infection, perforation, and bleeding at insertion. The IUD most likely will need to be removed at the time of treatment, but until then, the woman is at risk for pregnancy.
4 2 4 2
Ovarian cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 Comment: Women with ovarian cancer who undergo fertility-sparing treatment and need contraception may use an IUD.
Uterine fibroids 2 2 Evidence: Among women with uterine fibroids using an LNG-IUD, most experienced improvements in serum levels of hemoglobin, hematocrit, and ferritin and in menstrual blood loss (115). Rates of LNG-IUD expulsion were higher in women with uterine fibroids (11%) than in women without fibroids (0%–3%); these findings were either not statistically significant or significance testing was not conducted (115). Rates of expulsion found in noncomparative studies ranged from 0%–20% (115).
Comment: Women with heavy or prolonged bleeding should be assigned the category for that condition.
Anatomical abnormalities
a. Distorted uterine cavity (any congenital or acquired uterine abnormality distorting the uterine cavity in a manner that is incompatible with IUD insertion) 4 4 Comment: An anatomical abnormality that distorts the uterine cavity might preclude proper IUD placement.
b. Other abnormalities (including cervical stenosis or cervical lacerations) not distorting the uterine cavity or interfering with IUD insertion 2 2
Pelvic inflammatory disease Initiation Continuation Initiation Continuation
a. Past PID Comment: IUDs do not protect against STDs, including HIV, or PID. In women at low risk for STDs, IUD insertion poses little risk for PID.
   i. With subsequent pregnancy 1 1 1 1
   ii. Without subsequent pregnancy 2 2 2 2
b. Current PID 4 2 4 2 Clarification (continuation): Treat the PID using appropriate antibiotics. The IUD usually does not need to be removed if the woman wants to continue using it. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STDs and PID.
Evidence: Among IUD users treated for PID, clinical course did not differ regardless of whether the IUD was removed or left in place (116).
Sexually transmitted diseases Initiation Continuation Initiation Continuation
a. Current purulent cervicitis or chlamydial infection or gonococcal infection 4 2 4 2 Clarification (continuation): Treat the STD using appropriate antibiotics. The IUD usually does not need to be removed if the woman wants to continue using it. Continued use of an IUD depends on the woman’s informed choice and her current risk factors for STDs and PID.
Evidence: Among women who had an IUD inserted, the absolute risk for subsequent PID was low among women with STD at the time of insertion but greater than among women with no STD at the time of IUD insertion (117123).
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) 2 2 2 2
c. Other factors related to STDs 2 2 2 2 Clarification (initiation): Most women do not require additional STD screening at the time of IUD insertion. If a woman with risk factors for STDs has not been screened for gonorrhea and chlamydia according to CDC STD treatment guidelines (124), screening may be performed at the time of IUD insertion and insertion should not be delayed.
Evidence: Women who undergo same-day STD screening and IUD insertion have low incidence rates of PID. Algorithms for predicting PID among women with risk factors for STDs have poor predictive value. Risk for PID among women with risk factors for STDs is low (125).
HIV
High risk for HIV Initiation Continuation Initiation Continuation Evidence: Among women at risk for HIV, Cu-IUD use did not increase risk for HIV acquisition (126136).
2 2 2 2
HIV infection
For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Evidence: Among IUD users, limited evidence shows a low risk for PID among HIV-infected women using IUDs and no higher risk for pelvic infectious complications in HIV-infected than in HIV-noninfected women or among women with varying degrees of HIV severity. IUD use did not adversely affect progression of HIV during 6–45 months of follow-up or when compared with hormonal contraceptive use among HIV-infected women. Furthermore, IUD use among HIV-infected women was not associated with increased risk for transmission to sex partners or with increased genital viral shedding (137).
a. Clinically well receiving ARV therapy 1 1 1 1
b. Not clinically well or not receiving ARV therapy 2 1 2 1
Other Infections
Schistosomiasis
Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 1 1
b. Fibrosis of the liver (if severe, see Cirrhosis section) 1 1
Tuberculosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation Initiation Continuation
a. Nonpelvic 1 1 1 1
b. Pelvic 4 3 4 3 Comment: Insertion of an IUD might substantially worsen the condition.
Malaria 1 1
Endocrine Conditions
Diabetes
Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease 1 1
b. Nonvascular disease Evidence: Limited evidence on the use of the LNG-IUD among women with insulin-dependent or non–insulin-dependent diabetes suggests that these methods have little effect on short-term or long-term diabetes control (e.g., glycosylated hemoglobin levels), hemostatic markers, or lipid profile (138,139).
   i. Non-insulin dependent 1 2
   ii. Insulin dependent 1 2
c. Nephropathy, retinopathy, or neuropathy 1 2
d. Other vascular disease or diabetes of >20 years’ duration 1 2
Thyroid disorders
a. Simple goiter 1 1
b. Hyperthyroid 1 1
c. Hypothyroid 1 1
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease) 1 1 Evidence: Although two case reports described three women with IBD who experienced exacerbation of disease 5 days–25 months after LNG-IUD insertion, no comparative studies have examined the safety of IUD use among women with IBD (140).
Gallbladder disease
a. Symptomatic
i. Treated by cholecystectomy 1 2
ii. Medically treated 1 2
iii. Current 1 2
b. Asymptomatic 1 2
History of cholestasis
a. Pregnancy related 1 1
b. Past COC related 1 2 Comment: Concern exists that history of COC related cholestasis might predict subsequent cholestasis with LNG use. Whether risk exists with use of LNG-IUD is unclear.
Viral hepatitis
a. Acute or flare 1 1
b. Carrier 1 1
c. Chronic 1 1
Cirrhosis
Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated) 1 1
b. Severe (decompensated) 1 3
Liver tumors
Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
   i. Focal nodular hyperplasia 1 2
   ii. Hepatocellular adenoma 1 3 Comment: No evidence is available about hormonal contraceptive use in women with hepatocellular adenoma. COC use in healthy women is associated with development and growth of hepatocellular adenoma; whether other hormonal contraceptives have similar effects is not known.
b. Malignant (hepatoma) 1 3
Respiratory Conditions
Cystic fibrosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 Clarification: Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
Anemias
Thalassemia 2 1 Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.
Sickle cell disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
2 1 Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.
Iron deficiency anemia 2 1 Comment: Concern exists about an increased risk for blood loss with Cu-IUDs.
Solid Organ Transplantation
Solid organ transplantation
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation Initiation Continuation Evidence: No comparative studies have examined IUD use among transplant patients. Four case reports of transplant patients using IUDs provided inconsistent results, including beneficial effects and contraceptive failures (141).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy 3 2 3 2
b. Uncomplicated 2 2 2 2
Drug Interactions
Antiretroviral therapy Initiation Continuation Initiation Continuation Clarification: No known interaction exists between ARV therapy and IUD use. However, IUD insertion is classified as category 2 if the woman is not clinically well or not receiving ARV therapy. Otherwise, both insertion and continuation are classified as category 1 (see HIV Infection section).
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
   i. Abacavir (ABC) 1/2 1 1/2 1
   ii. Tenofovir (TDF) 1/2 1 1/2 1
   iii. Zidovudine (AZT) 1/2 1 1/2 1
   iv. Lamivudine (3TC) 1/2 1 1/2 1
   v. Didanosine (DDI) 1/2 1 1/2 1
   vi. Emtricitabine (FTC) 1/2 1 1/2 1
   vii. Stavudine (D4T) 1/2 1 1/2 1
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
   i. Efavirenz (EFV) 1/2 1 1/2 1
   ii. Etravirine (ETR) 1/2 1 1/2 1
   iii. Nevirapine (NVP) 1/2 1 1/2 1
   iv. Rilpivirine (RPV) 1/2 1 1/2 1
c. Ritonavir-boosted protease inhibitors
   i. Ritonavir-boosted atazanavir (ATV/r) 1/2 1 1/2 1
   ii. Ritonavir-boosted darunavir (DRV/r) 1/2 1 1/2 1
   iii. Ritonavir-boosted fosamprenavir (FPV/r) 1/2 1 1/2 1
   iv. Ritonavir-boosted lopinavir (LPV/r) 1/2 1 1/2 1
   v. Ritonavir-boosted saquinavir (SQV/r) 1/2 1 1/2 1
   vi. Ritonavir-boosted tipranavir (TPV/r) 1/2 1 1/2 1
d. Protease inhibitors without ritonavir
   i. Atazanavir (ATV) 1/2 1 1/2 1
   ii. Fosamprenavir (FPV) 1/2 1 1/2 1
   iii. Indinavir (IDV) 1/2 1 1/2 1
   iv. Nelfinavir (NFV) 1/2 1 1/2 1
e. CCR5 co-receptor antagonists
   i. Maraviroc (MVC) 1/2 1 1/2 1
f. HIV integrase strand transfer inhibitors
   i. Raltegravir (RAL) 1/2 1 1/2 1
   ii. Dolutegravir (DTG) 1/2 1 1/2 1
   iii. Elvitegravir (EVG) 1/2 1 1/2 1
g. Fusion inhibitors
   i. Enfuvirtide 1/2 1 1/2 1
Anticonvulsant therapy
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine) 1 1 Evidence: Limited evidence suggests use of certain anticonvulsants does not interfere with the contraceptive effectiveness of the LNG-IUD (142).
b. Lamotrigine 1 1 Evidence: No drug interactions have been reported among women with epilepsy who are receiving lamotrigine and using the LNG-IUD (143).
Antimicrobial therapy
a. Broad-spectrum antibiotics 1 1
b. Antifungals 1 1
c. Antiparasitics 1 1
d. Rifampin or rifabutin therapy 1 1 Evidence: One cross-sectional survey found that rifabutin had no impact on the effectiveness of the LNG-IUD (142).
Psychotropic medications Comment: For many common psychotropic agents, limited or no theoretical concern exists for clinically significant drug interactions when co-administered with hormonal contraceptives. However, either no or very limited data exist examining potential interactions for these classes of medications.
a. SSRIs 1 1
St. John’s wort 1 1

Abbreviations: ARV = antiretroviral; BMI = body mass index; COC = combined oral contraceptive; Cu-IUD = copper-containing IUD; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; IUD = intrauterine device; LDL = low-density lipoprotein; LNG = levonorgestrel; LNG-IUD = levonorgestrel-releasing IUD; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; SLE = systemic lupus erythematosus; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted disease; VTE = venous thromboembolism.

References

  1. Cramer DW, Schiff I, Schoenbaum SC, et al. Tubal infertility and the intrauterine device. N Engl J Med 1985;312:941–7. CrossRef PubMed
  2. Daling JR, Weiss NS, Metch BJ, et al. Primary tubal infertility in relation to the use of an intrauterine device. N Engl J Med 1985;312:937–41. CrossRef PubMed
  3. Daling JR, Weiss NS, Voigt LF, McKnight B, Moore DE. The intrauterine device and primary tubal infertility. N Engl J Med 1992;326:203–4. CrossRef PubMed
  4. Delbarge W, Bátár I, Bafort M, et al. Return to fertility in nulliparous and parous women after removal of the GyneFix intrauterine contraceptive system. Eur J Contracept Reprod Health Care 2002;7:24–30. CrossRef PubMed
  5. Doll H, Vessey M, Painter R. Return of fertility in nulliparous women after discontinuation of the intrauterine device: comparison with women discontinuing other methods of contraception. BJOG 2001;108:304–14. CrossRef PubMed
  6. Hubacher D, Lara-Ricalde R, Taylor DJ, Guerra-Infante F, Guzmán-Rodríguez R. Use of copper intrauterine devices and the risk of tubal infertility among nulligravid women. N Engl J Med 2001;345:561–7. CrossRef PubMed
  7. Skjeldestad FE, Bratt H. Return of fertility after use of IUDs (Nova-T, MLCu250 and MLCu375). Adv Contracept 1987;3:139–45. CrossRef PubMed
  8. Urbach DR, Marrett LD, Kung R, Cohen MM. Association of perforation of the appendix with female tubal infertility. Am J Epidemiol 2001;153:566–71. CrossRef PubMed
  9. Wilson JC. A prospective New Zealand study of fertility after removal of copper intrauterine contraceptive devices for conception and because of complications: a four-year study. Am J Obstet Gynecol 1989;160:391–6. CrossRef PubMed
  10. US Department of Health and Human Services. Healthy people 2020: Maternal, infant, and child health objectives. Washington, DC: US Department of Health and Human Services; 2015. http://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health/objectives
  11. Annus J, Brat T, Diethelm MP, et al. ; World Health Organization Special. Comparative multicentre trial of three IUDs inserted immediately following delivery of the placenta. Contraception 1980;22:9–18. CrossRef PubMed
  12. Apelo RA, Waszak CS. Postpartum IUD insertions in Manila, Philippines. Adv Contracept 1985;1:319–28.
  13. Baldwin MK, Edelman AB, Lim JY, Nichols MD, Bednarek PH, Jensen JT. Intrauterine device placement at 3 versus 6weeks postpartum: a randomized trial. Contraception 2016;93:356–63. CrossRef PubMed
  14. Bonilla Rosales F, Aguilar Zamudio ME, Cázares Montero ML, Hernández Ortiz ME, Luna Ruiz MA. [Factors for expulsion of intrauterine device Tcu380A applied immediately postpartum and after a delayed period]. Rev Med Inst Mex Seguro Soc 2005;43:5–10. PubMed
  15. Braniff K, Gomez E, Muller R. A randomised clinical trial to assess satisfaction with the levonorgestrel- releasing intrauterine system inserted at caesarean section compared to postpartum placement. Aust N Z J Obstet Gynaecol 2015;55:279–83. CrossRef PubMed
  16. Bryant AG, Kamanga G, Stuart GS, Haddad LB, Meguid T, Mhango C. Immediate postpartum versus 6-week postpartum intrauterine device insertion: a feasibility study of a randomized controlled trial. Afr J Reprod Health 2013;17:72–9. PubMed
  17. Caliskan E, Ozturk N, Dilbaz BO, Dilbaz S. Analysis of risk factors associated with uterine perforation by intrauterine devices. Eur J Contracep Reprod 2003;8:150–5.
  18. Çelen S, Möröy P, Sucak A, Aktulay A, Dani&scedilman N. Clinical outcomes of early postplacental insertion of intrauterine contraceptive devices. Contraception 2004;69:279–82. CrossRef PubMed
  19. Çelen &Scedil, Sucak A, Y&inodotld&inodotz Y, Dan&inodot&scedilman N. Immediate postplacental insertion of an intrauterine contraceptive device during cesarean section. Contraception 2011;84:240–3. CrossRef PubMed
  20. Chen BA, Reeves MF, Hayes JL, Hohmann HL, Perriera LK, Creinin MD. Postplacental or delayed insertion of the levonorgestrel intrauterine device after vaginal delivery: a randomized controlled trial. Obstet Gynecol 2010;116:1079–87. CrossRef PubMed
  21. Chen JH, Wu SC, Shao WQ, et al. The comparative trial of TCu 380A IUD and progesterone-releasing vaginal ring used by lactating women. Contraception 1998;57:371–9. CrossRef PubMed
  22. Cohen R, Sheeder J, Arango N, Teal SB, Tocce K. Twelve-month contraceptive continuation and repeat pregnancy among young mothers choosing postdelivery contraceptive implants or postplacental intrauterine devices. Contraception 2016;93:178–83. CrossRef PubMed
  23. Dahlke JD, Terpstra ER, Ramseyer AM, Busch JM, Rieg T, Magann EF. Postpartum insertion of levonorgestrel—intrauterine system at three time periods: a prospective randomized pilot study. Contraception 2011;84:244–8. CrossRef PubMed
  24. Dias T, Abeykoon S, Kumarasiri S, Gunawardena C, Padeniya T, D’Antonio F. Use of ultrasound in predicting success of intrauterine contraceptive device insertion immediately after delivery. Ultrasound Obstet Gynecol 2015;46:104–8.
  25. Elsedeek MS. Puerperal and menstrual bleeding patterns with different types of contraceptive device fitted during elective cesarean delivery. Int J Gynaecol Obstet 2012;116:31–4. CrossRef PubMed
  26. Elsedeek MS. Five-year follow-up of two types of contraceptive device fitted during elective cesarean delivery. Int J Gynaecol Obstet 2015;130:179–82. CrossRef PubMed
  27. El-Shafei MM, Mashali A, Hassan EO, El-Boghdad L, El-Lakkany N. Postpartum and postabortion intrauterine device insertion unmet needs of safe reproductive health: three years experience of Mansoura University Hospital. J Egypt Soc Obstet Gynecol 2000;26:253–62.
  28. Eroglu K, Akkuzu G, Vural G, et al. Comparison of efficacy and complications of IUD insertion in immediate postplacental/early postpartum period with interval period: 1 year follow-up. Contraception 2006;74:376–81. CrossRef PubMed
  29. Gueye M, Gaye YF, Diouf AA, et al. Trancesarean intra-uterine device. Pilot study performed at Dakar teaching hospital. [French]. J Gynecol Obstet Biol Reprod (Paris) 2013;42:585–90. CrossRef PubMed
  30. Gupta S, Malik S, Sinha R, Shyamsunder S, Mittal MK. Association of the Position of the Copper T 380A as Determined by the Ultrasonography Following its Insertion in the Immediate Postpartum Period with the Subsequent Complications: An Observational Study. J Obstet Gynaecol India 2014;64:349–53. CrossRef PubMed
  31. Hagbard L, Ingemanson CA, Sorbe B. Early postpartum insertion of copper IUD. Contraception 1978;17:355–63. CrossRef PubMed
  32. Hayes JL, Cwiak C, Goedken P, Zieman M. A pilot clinical trial of ultrasound-guided postplacental insertion of a levonorgestrel intrauterine device. Contraception 2007;76:292–6. CrossRef PubMed
  33. Jatlaoui TC, Marcus M, Jamieson DJ, Goedken P, Cwiak C. Postplacental intrauterine device insertion at a teaching hospital. Contraception 2014;89:528–33. CrossRef PubMed
  34. Kumar S, Sethi R, Balasubramaniam S, et al. Women’s experience with postpartum intrauterine contraceptive device use in India. Reprod Health 2014;11:32. CrossRef PubMed
  35. Laes E, Lehtovirta P, Weintraub D, Pyörälä T, Luukkainen T. Early puerperal insertions of copper-T-200. Contraception 1975;11:289–95. CrossRef PubMed
  36. Lara Ricalde R, Menocal Tobías G, Ramos Pérez C, Velázquez Ramírez N. [Random comparative study between intrauterine device Multiload Cu375 and TCu 380a inserted in the postpartum period]. Ginecol Obstet Mex 2006;74:306–11. PubMed
  37. Lavin P, Bravo C, Waszak C. Comparison of T Cu 200 and Progestasert IUDs. Contracept Deliv Syst 1983;4:143–7. PubMed
  38. Lavin P, Waszak C, Bravo C. Preliminary report on a postpartum CuT 200 study, Santiago, Chile. Int J Gynaecol Obstet 1983;21:71–5. CrossRef PubMed
  39. Lester F, Kakaire O, Byamugisha J, et al. Intracesarean insertion of the Copper T380A versus 6 weeks postcesarean: a randomized clinical trial. Contraception 2015;91:198–203. CrossRef PubMed
  40. Letti Müller AL, Lopes Ramos JG, Martins-Costa SH, et al. Transvaginal ultrasonographic assessment of the expulsion rate of intrauterine devices inserted in the immediate postpartum period: a pilot study. Contraception 2005;72:192–5. CrossRef PubMed
  41. Levi E, Cantillo E, Ades V, Banks E, Murthy A. Immediate postplacental IUD insertion at cesarean delivery: a prospective cohort study. Contraception 2012;86:102–5. CrossRef PubMed
  42. Levi EE, Stuart GS, Zerden ML, Garrett JM, Bryant AG. Intrauterine device placement during cesarean delivery and continued use 6 months postpartum: a randomized controlled trial. Obstet Gynecol 2015;126:5–11. CrossRef PubMed
  43. Mishra S. Evaluation of Safety, Efficacy, and Expulsion of Post-Placental and Intra-Cesarean Insertion of Intrauterine Contraceptive Devices (PPIUCD). J Obstet Gynaecol India 2014;64:337–43. CrossRef PubMed
  44. Morrison C, Waszak C, Katz K, Diabaté F, Mate EM. Clinical outcomes of two early postpartum IUD insertion programs in Africa. Contraception 1996;53:17–21. CrossRef PubMed
  45. Nelson AL, Chen S, Eden R. Intraoperative placement of the Copper T-380 intrauterine devices in women undergoing elective cesarean delivery: a pilot study. Contraception 2009;80:81–3. CrossRef PubMed
  46. Newton J, Harper M, Chan KK. Immediate post-placental insertion of intrauterine contraceptive devices. Lancet 1977;310:272–4. CrossRef PubMed
  47. Prema K, Gayathri TL, Philips FS. Comparative study of early postpartum, postabortal and interval insertion of Cu T 200 mm2 device. J Obstet Gynaecol India 1978;28:946–8. PubMed
  48. Puzey M. Mirena at caesarean section. Eur J Contracep Reprod 2005;10:164–7.
  49. Ragab A, Hamed HO, Alsammani MA, et al. Expulsion of Nova-T380, Multiload 375, and Copper-T380A contraceptive devices inserted during cesarean delivery. Int J Gynaecol Obstet 2015;130:174–8. CrossRef PubMed
  50. Shukla M, Qureshi S; Chandrawati. Post-placental intrauterine device insertion—a five year experience at a tertiary care centre in north India. Indian J Med Res 2012;136:432–5. PubMed
  51. Singal S, Bharti R, Dewan R, et al. Clinical Outcome of Postplacental Copper T 380A Insertion in Women Delivering by Caesarean Section. J Clin Diagn Res 2014;8:OC01–04. PubMed
  52. Stuart GS, Bryant AG, O’Neill E, Doherty IA. Feasibility of postpartum placement of the levonorgestrel intrauterine system more than 6 h after vaginal birth. Contraception 2012;85:359–62. CrossRef PubMed
  53. Stuart GS, Lesko CR, Stuebe AM, Bryant AG, Levi EE, Danvers AI. A randomized trial of levonorgestrel intrauterine system insertion 6 to 48 h compared to 6 weeks after vaginal delivery; lessons learned. Contraception 2015;91:284–8. CrossRef PubMed
  54. Thiery M, Van Kets H, Van der Pas H. Immediate post-placental IUD insertion: the expulsion problem. Contraception 1985;31:331–49. CrossRef PubMed
  55. Van Der Pas MT, Delbeke L, Van Dets H. Comparative performance of two copper-wired IUDs (ML Cu 250 and T Cu 200: immediate postpartum and interval insertion. Contracept Deliv Syst 1980;1:27–35. PubMed
  56. Welkovic S, Costa LO, Faúndes A, de Alencar Ximenes R, Costa CF. Post-partum bleeding and infection after post-placental IUD insertion. Contraception 2001;63:155–8. CrossRef PubMed
  57. Whitaker AK, Endres LK, Mistretta SQ, Gilliam ML. Postplacental insertion of the levonorgestrel intrauterine device after cesarean delivery vs. delayed insertion: a randomized controlled trial. Contraception 2014;89:534–9. CrossRef PubMed
  58. Woo CJ, Alamgir H, Potter JE. Women’s experiences after Planned Parenthood’s exclusion from a family planning program in Texas. Contraception 2016;93:298–302. CrossRef PubMed
  59. Wu SC; Research Group on Failure Causes and Prevention Measures of Intrauterine Device. [Efficacy of intrauterine device TCu380A when inserted in four different periods]. Zhonghua Fu Chan Ke Za Zhi 2009;44:431–5. PubMed
  60. Xu J, Yang X, Gu X, et al. Comparison between two techniques used in immediate postplacental insertion of TCu 380A intrauterine device: 36-month follow-up. Reprod Contracept 1999;10:156–62. PubMed
  61. Xu J, Zhuang L, Yu G. [Comparison of two techniques used in immediate postplacental insertion of TCu 380A intrauterine device: 12 month follow-up of 910 cases]. Zhonghua Fu Chan Ke Za Zhi 1997;32:354–7. PubMed
  62. Xu JX, Rivera R, Dunson TR, et al. A comparative study of two techniques used in immediate postplacental insertion (IPPI) of the Copper T-380A IUD in Shanghai, People’s Republic of China. Contraception 1996;54:33–8. CrossRef PubMed
  63. Braniff K, Gomez E, Muller R. A randomised clinical trial to assess satisfaction with the levonorgestrel- releasing intrauterine system inserted at caesarean section compared to postpartum placement. Aust N Z J Obstet Gynaecol 2015;55:279–83. CrossRef PubMed
  64. Phillips SJ, Tepper NK, Kapp N, Nanda K, Temmerman M, Curtis KM. Progestogen-only contraceptive use among breastfeeding women: a systematic review. Contraception 2015;S0010-7824(15)00585-5. PubMed
  65. Berry-Bibee E, Tepper N, Jatlaoui T, Whiteman M, Jamieson D, Curtis K. The safety of intrauterine devices in breastfeeding women: a systematic review. Contraception . In press 2016.
  66. Steenland MW, Tepper NK, Curtis KM, Kapp N. Intrauterine contraceptive insertion postabortion: a systematic review. Contraception 2011;84:447–64. CrossRef PubMed
  67. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. Contraception 1998;57:315–24. . CrossRef PubMed
  68. Heinemann LA, Assmann A, DoMinh T, Garbe E. Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Eur J Contracept Reprod Health Care 1999;4:67–73. CrossRef PubMed
  69. Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet 1999;354:1610–1. CrossRef PubMed
  70. Kingman CE, Kadir RA, Lee CA, Economides DL. The use of levonorgestrel-releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding disorders. BJOG 2004;111:1425–8. CrossRef PubMed
  71. Lukes AS, Reardon B, Arepally G. Use of the levonorgestrel-releasing intrauterine system in women with hemostatic disorders. Fertil Steril 2008;90:673–7. CrossRef PubMed
  72. Pisoni CN, Cuadrado MJ, Khamashta MA, Hunt BJ. Treatment of menorrhagia associated with oral anticoagulation: efficacy and safety of the levonorgestrel releasing intrauterine device (Mirena coil). Lupus 2006;15:877–80. CrossRef PubMed
  73. Schaedel ZE, Dolan G, Powell MC. The use of the levonorgestrel-releasing intrauterine system in the management of menorrhagia in women with hemostatic disorders. Am J Obstet Gynecol 2005;193:1361–3. CrossRef PubMed
  74. Wilson W, Taubert KA, Gewitz M, et al. American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007;116:1736–54. CrossRef PubMed
  75. Tepper NK, Paulen ME, Marchbanks PA, Curtis KM. Safety of contraceptive use among women with peripartum cardiomyopathy: a systematic review. Contraception 2010;82:95–101. CrossRef PubMed
  76. The Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Little, Brown and Co; 1994.
  77. Bernatsky S, Clarke A, Ramsey-Goldman R, et al. Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus. Rheumatology (Oxford) 2004;43:1178–81. CrossRef PubMed
  78. Bernatsky S, Ramsey-Goldman R, Gordon C, et al. Factors associated with abnormal Pap results in systemic lupus erythematosus. Rheumatology (Oxford) 2004;43:1386–9. CrossRef PubMed
  79. Chopra N, Koren S, Greer WL, et al. Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol 2002;29:1683–8. PubMed
  80. Esdaile JM, Abrahamowicz M, Grodzicky T, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2001;44:2331–7. CrossRef PubMed
  81. Julkunen HA, Kaaja R, Friman C. Contraceptive practice in women with systemic lupus erythematosus. Br J Rheumatol 1993;32:227–30. CrossRef PubMed
  82. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 1997;145:408–15. CrossRef PubMed
  83. McAlindon T, Giannotta L, Taub N, D’Cruz D, Hughes G. Environmental factors predicting nephritis in systemic lupus erythematosus. Ann Rheum Dis 1993;52:720–4. CrossRef PubMed
  84. McDonald J, Stewart J, Urowitz MB, Gladman DD. Peripheral vascular disease in patients with systemic lupus erythematosus. Ann Rheum Dis 1992;51:56–60. CrossRef PubMed
  85. Mintz G, Gutiérrez G, Delezé M, Rodríguez E. Contraception with progestagens in systemic lupus erythematosus. Contraception 1984;30:29–38. CrossRef PubMed
  86. Petri M. Musculoskeletal complications of systemic lupus erythematosus in the Hopkins Lupus Cohort: an update. Arthritis Care Res 1995;8:137–45. CrossRef PubMed
  87. Petri M. Lupus in Baltimore: evidence-based ‘clinical pearls’ from the Hopkins Lupus Cohort. Lupus 2005;14:970–3. CrossRef PubMed
  88. Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005;353:2539–49. CrossRef PubMed
  89. Sarabi ZS, Chang E, Bobba R, et al. Incidence rates of arterial and venous thrombosis after diagnosis of systemic lupus erythematosus. Arthritis Rheum 2005;53:609–12. CrossRef PubMed
  90. Somers E, Magder LS, Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol 2002;29:2531–6. PubMed
  91. Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 1976;60:221–5. CrossRef PubMed
  92. Julkunen HA. Oral contraceptives in systemic lupus erythem­atosus: side-effects and influence on the activity of SLE. Scand J Rheumatol 1991;20:427–33. CrossRef PubMed
  93. Jungers P, Dougados M, Pélissier C, et al. Influence of oral contraceptive therapy on the activity of systemic lupus erythematosus. Arthritis Rheum 1982;25:618–23. CrossRef PubMed
  94. Petri M, Kim MY, Kalunian KC, et al. OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005;353:2550–8. CrossRef PubMed
  95. Choojitarom K, Verasertniyom O, Totemchokchyakarn K, Nantiruj K, Sumethkul V, Janwityanujit S. Lupus nephritis and Raynaud’s phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies. Clin Rheumatol 2008;27:345–51. CrossRef PubMed
  96. Wahl DG, Guillemin F, de Maistre E, Perret C, Lecompte T, Thibaut G. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus—a meta-analysis. Lupus 1997;6:467–73. CrossRef PubMed
  97. Tepper N, Whiteman M, Zapata L, Marchbanks P, Curtis K. Safety of hormonal contraceptives among women with migraine: a systematic review. Contraception 2016. Epub May 3, 2016. . CrossRef
  98. Tepper NK, Whiteman MK, Marchbanks PA, James AH, Curtis KM. Progestin-only contraception and thromboembolism: a systematic review. Contraception 2016. Epub May 3, 2016. CrossRef PubMed
  99. Pagano HP, Zapata LB, Berry-Bibee EN, Nanda K, Curtis KM. Safety of hormonal contraception and intrauterine devices among women with depressive and bipolar disorders: a systematic review. Contraception 2016. Epub June 27, 2016. CrossRef
  100. Barrington JW, Arunkalaivanan AS, Abdel-Fattah M. Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. Eur J Obstet Gynecol Reprod Biol 2003;108:72–4. CrossRef PubMed
  101. Gupta B, Mittal S, Misra R, Deka D, Dadhwal V. Levonorgestrel-releasing intrauterine system vs. transcervical endometrial resection for dysfunctional uterine bleeding. Int J Gynaecol Obstet 2006;95:261–6. CrossRef PubMed
  102. Hurskainen R, Teperi J, Rissanen P, et al. Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial.[see comment]. Lancet 2001;357:273–7. CrossRef PubMed
  103. Istre O, Trolle B. Treatment of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection. Fertil Steril 2001;76:304–9. CrossRef PubMed
  104. Koh SC, Singh K. The effect of levonorgestrel-releasing intrauterine system use on menstrual blood loss and the hemostatic, fibrinolytic/inhibitor systems in women with menorrhagia. J Thromb Haemost 2007;5:133–8. CrossRef PubMed
  105. Lethaby AE, Cooke I, Rees M. Progesterone/progestogen releasing intrauterine systems versus either placebo or any other medication for heavy menstrual bleeding. Cochrane Database Syst Rev 2000;(2):CD002126. PubMed
  106. Magalhães J, Aldrighi JM, de Lima GR. Uterine volume and menstrual patterns in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas. Contraception 2007;75:193–8. CrossRef PubMed
  107. Stewart A, Cummins C, Gold L, Jordan R, Phillips W. The effectiveness of the levonorgestrel-releasing intrauterine system in menorrhagia: a systematic review. BJOG 2001;108:74–86. CrossRef PubMed
  108. Fedele L, Bianchi S, Zanconato G, Portuese A, Raffaelli R. Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis. Fertil Steril 2001;75:485–8. CrossRef PubMed
  109. Lockhat FBE, Emembolu J, Konje JC. The effect of a levonorgestrel intrauterine system (LNG-IUS) on symptomatic endometriosis. Fertil Steril 2002;77(Suppl 1):S24. CrossRef
  110. Petta CA, Ferriani RA, Abrao MS, et al. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 2005;20:1993–8. CrossRef PubMed
  111. Vercellini P, Aimi G, Panazza S, De Giorgi O, Pesole A, Crosignani PG. A levonorgestrel-releasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study. Fertil Steril 1999;72:505–8. CrossRef PubMed
  112. Vercellini P, Frontino G, De Giorgi O, Aimi G, Zaina B, Crosignani PG. Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Fertil Steril 2003;80:305–9. CrossRef PubMed
  113. Gaffield ME, Kapp N, Curtis KM. Combined oral contraceptive and intrauterine device use among women with gestational trophoblastic disease. Contraception 2009;80:363–71. CrossRef PubMed
  114. Whiteman MK, Zapata LB, Tepper NK, Marchbanks PA, Curtis KM. Use of contraceptive methods among women with endometrial hyperplasia: a systematic review. Contraception 2010;82:56–63. CrossRef PubMed
  115. Zapata LB, Whiteman MK, Tepper NK, Jamieson DJ, Marchbanks PA, Curtis KM. Intrauterine device use among women with uterine fibroids: a systematic review. Contraception 2010;82:41–55. CrossRef PubMed
  116. Tepper NK, Steenland MW, Gaffield ME, Marchbanks PA, Curtis KM. Retention of intrauterine devices in women who acquire pelvic inflammatory disease: a systematic review. Contraception 2013;87:655–60. CrossRef PubMed
  117. Faúndes A, Telles E, Cristofoletti ML, Faúndes D, Castro S, Hardy E. The risk of inadvertent intrauterine device insertion in women carriers of endocervical Chlamydia trachomatis. Contraception 1998;58:105–9. CrossRef PubMed
  118. Ferraz do Lago R, Simões JA, Bahamondes L, Camargo RP, Perrotti M, Monteiro I. Follow-up of users of intrauterine device with and without bacterial vaginosis and other cervicovaginal infections. Contraception 2003;68:105–9. CrossRef PubMed
  119. Morrison CS, Sekadde-Kigondu C, Miller WC, Weiner DH, Sinei SK. Use of sexually transmitted disease risk assessment algorithms for selection of intrauterine device candidates. Contraception 1999;59:97–106. CrossRef PubMed
  120. Pap-Akeson M, Solheim F, Thorbert G, Akerlund M. Genital tract infections associated with the intrauterine contraceptive device can be reduced by inserting the threads into the uterine cavity. Br J Obstet Gynaecol 1992;99:676–9. CrossRef PubMed
  121. Sinei SK, Schulz KFLP, Lamptey PR, et al. Preventing IUCD-related pelvic infection: the efficacy of prophylactic doxycycline at insertion. Br J Obstet Gynaecol 1990;97:412–9. CrossRef PubMed
  122. Skjeldestad FE, Halvorsen LE, Kahn H, Nordbø SA, Saake K. IUD users in Norway are at low risk for genital C. trachomatis infection. Contraception 1996;54:209–12. CrossRef PubMed
  123. Walsh TL, Bernstein GS, Grimes DA, Frezieres R, Bernstein L, Coulson AH; IUD Study Group. Effect of prophylactic antibiotics on morbidity associated with IUD insertion: results of a pilot randomized controlled trial. Contraception 1994;50:319–27. CrossRef PubMed
  124. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-03). PubMed
  125. Jatlaoui TC, Simmons KB, Curtis KM. The safety of intrauterine contraception initiation among women with current asymptomatic cervical infections or at increased risk of sexually transmitted infections. Contraception 2016. Epub June 1, 2016. CrossRef
  126. Carael M, Van de Perre PH, Lepage PH, et al. Human immunodeficiency virus transmission among heterosexual couples in Central Africa. AIDS 1988;2:201–5. PubMed
  127. European Study Group on Heterosexual Transmission of HIV. Comparison of female to male and male to female transmission of HIV in 563 stable couples. BMJ 1992;304:809–13. CrossRef PubMed
  128. Kapiga SH, Lyamuya EF, Lwihula GK, Hunter DJ. The incidence of HIV infection among women using family planning methods in Dar es Salaam, Tanzania. AIDS 1998;12:75–84. . CrossRef PubMed
  129. Kapiga SH, Shao JF, Lwihula GK, Hunter DJ. Risk factors for HIV infection among women in Dar-es-Salaam, Tanzania. J Acquir Immune Defic Syndr 1994;7:301–9. PubMed
  130. Mann JM, Nzilambi N, Piot P, et al. HIV infection and associated risk factors in female prostitutes in Kinshasa, Zaire. AIDS 1988;2:249–54. CrossRef PubMed
  131. Martin HL , Nyange PM, Richardson BA, et al. Hormonal contraception, sexually transmitted diseases, and risk of heterosexual transmission of human immunodeficiency virus type 1. J Infect Dis 1998;178:1053–9. CrossRef PubMed
  132. Mali JK, Hunter DJ, Maggwa BN, Tukei PM. Contraceptive use and the risk of HIV infection in Nairobi, Kenya. Int J Gynaecol Obstet 1995;48:61–7. CrossRef PubMed
  133. Nicolosi A, Corrêa Leite ML, Musicco M, Arici C, Gavazzeni G, Lazzarin A; Italian Study Group on HIV Heterosexual Transmission. The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples.[comment]. Epidemiology 1994;5:570–5. CrossRef PubMed
  134. Plourde PJ, Plummer FA, Pepin J, et al. Human immunodeficiency virus type 1 infection in women attending a sexually transmitted diseases clinic in Kenya.[comment]. J Infect Dis 1992;166:86–92. CrossRef PubMed
  135. Sinei SK, Fortney JA, Kigondu CS, et al. Contraceptive use and HIV infection in Kenyan family planning clinic attenders. Int J STD AIDS 1996;7:65–70. CrossRef PubMed
  136. Spence MR, Robbins SM, Polansky M, Schable CA. Seroprevalence of human immunodeficiency virus type I (HIV-1) antibodies in a family-planning population. Sex Transm Dis 1991;18:143–5. CrossRef PubMed
  137. Tepper NK, Curtis KM, Nanda K, Jamieson DJ. Safety of intrauterine devices among women with HIV: a systematic review. Contraception 2016. Epub June 22, 2016. CrossRef
  138. Grigoryan OR, Grodnitskaya EE, Andreeva EN, Shestakova MV, Melnichenko GA, Dedov II. Contraception in perimenopausal women with diabetes mellitus. Gynecol Endocrinol 2006;22:198–206. CrossRef PubMed
  139. Rogovskaya S, Rivera R, Grimes DA, et al. Effect of a levonorgestrel intrauterine system on women with type 1 diabetes: a randomized trial. Obstet Gynecol 2005;105:811–5. CrossRef PubMed
  140. Zapata LB, Paulen ME, Cansino C, Marchbanks PA, Curtis KM. Contraceptive use among women with inflammatory bowel disease: a systematic review. Contraception 2010;82:72–85. CrossRef PubMed
  141. Paulen ME, Folger SG, Curtis KM, Jamieson DJ. Contraceptive use among solid organ transplant patients: a systematic review. Contraception 2010;82:102–12. CrossRef PubMed
  142. Bounds W, Guillebaud J. Observational series on women using the contraceptive Mirena concurrently with anti-epileptic and other enzyme-inducing drugs. J Fam Plann Reprod Health Care 2002;28:78–80. CrossRef PubMed
  143. Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia 2005;46:1414–7. CrossRef PubMed

Appendix C

Classifications for Progestin-Only Contraceptives

Classifications for progestin-only contraceptives (POCs) include those for progestin-only implants, depot medroxyprogesterone acetate (DMPA; 150 mg intramuscularly or 104 mg subcutaneously), and progestin-only pills (POPs) ( Box C1) ( Table C1). POCs do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Return to your place in the textBOX C1. Categories for classifying progestin-only contraceptives

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE C1. Classifications for progestin-only contraceptives, including implants, depot medroxyprogesterone acetate, and progestin-only pills
Condition Category Clarifications/Evidence/Comments
Implants DMPA POPs
Personal Characteristics and Reproductive History
Pregnancy NA NA NA Clarification: Use of POCs is not required. No known harm to the woman, the course of her pregnancy, or the fetus occurs if POCs are inadvertently used during pregnancy. However, the relation between DMPA use during pregnancy and its effects on the fetus remains unclear.
Age Evidence: Most studies have found that women lose BMD during DMPA use but recover BMD after discontinuation. Limited evidence shows a weak association with fracture. However, one large study suggests that women who choose DMPA might be at higher risk for fracture before initiation (1). It is unclear whether adult women with long durations of DMPA use can regain BMD to baseline levels before entering menopause and whether adolescents can reach peak bone mass after discontinuation of DMPA. The relationship between these changes in BMD during the reproductive years and future fracture risk is unknown. Studies generally find no effect of POCs other than DMPA on BMD (148).
a. Menarche to <18 years 1 2 1
b. 18–45 years 1 1 1
c. >45 years 1 2 1
Parity
a. Nulliparous 1 1 1
b. Parous 1 1 1
Breastfeeding
a. <21 days postpartum 2 2 2 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49).
Evidence: Two small, randomized controlled trials found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at =6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (50,51).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
b. 21 to <30 days postpartum Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49).
Evidence: Two small, randomized controlled trials found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at =6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (50,51).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 2 2 2
   ii. Without other risk factors for VTE 2 2 2
c. 30–42 days postpartum Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49).
Evidence: Two small, randomized controlled trials found no adverse impact on breastfeeding with initiation of etonogestrel implants within 48 hours postpartum. Other studies found that initiation of POPs, injectables, and implants at =6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (50,51).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 1 1 1
   ii. Without other risk factors for VTE 1 1 1
d. >42 days postpartum 1 1 1 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (49).
Evidence: Overall, studies found that initiation of POPs, injectables, and implants at >6 weeks postpartum compared with nonhormonal use had no detrimental effect on breastfeeding outcomes or infant health, growth, and development in the first year postpartum. In general, these studies are of poor quality, lack standard definitions of breastfeeding or outcome measures, and have not included premature or ill infants (51).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, and certain perinatal complications and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
Postpartum (nonbreastfeeding women)
a. <21 days postpartum 1 1 1
b. 21–42 days postpartum
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 1 1 1
   ii. Without other risk factors for VTE 1 1 1
c. >42 days postpartum 1 1 1
Postabortion
a. First trimester 1 1 1 Clarification: POCs may be started immediately postabortion.

Evidence: Limited evidence suggests that no adverse side effects occur when implants (Norplant) or progestin-only injectables (NET-EN) are initiated after first trimester abortion (5255).

b. Second trimester 1 1 1 Clarification: POCs may be started immediately postabortion.
c. Immediate postseptic abortion 1 1 1 Clarification: POCs may be started immediately postabortion.
Past ectopic pregnancy 1 1 2 Comment: POP users have a higher absolute rate of ectopic pregnancy than do users of other POCs but still lower than women using no method.
History of pelvic surgery 1 1 1
Smoking
a. Age <35 years 1 1 1
b. Age =35 years
   i. <15 cigarettes per day 1 1 1
   ii. =15 cigarettes per day 1 1 1
Obesity
a. BMI =30 kg/m2 1 1 1
b. Menarche to <18 years and BMI =30 kg/m2 1 2 1 Evidence: Among adult women, generally no association has been found between baseline weight and weight gain among DMPA users compared with nonusers. Evidence is mixed for adolescent DMPA users, with some studies observing greater weight gain among obese compared with normal weight users but other studies showing no association; methodologic differences across studies might account for the differences in findings. Data on other POC methods and other adverse outcomes including weight gain are limited (5673).
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 1 1 Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent laparoscopic placement of an adjustable gastric band (74).
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) 1 1 3 Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent a biliopancreatic diversion; however, evidence from pharmacokinetic studies suggested conflicting results regarding oral contraceptive effectiveness among women who underwent a jejunoileal bypass (74).
Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to decrease oral contraceptive effectiveness, perhaps further decreased by postoperative complications such as long-term diarrhea, vomiting, or both.
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels) 2 3 2 Clarification: When multiple major risk factors exist, risk for cardiovascular disease might increase substantially. Certain POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs. The effects of DMPA might persist for some time after discontinuation.
Clarification: The recommendations apply to known preexisting medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See the U.S. Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usspr.htm).
Hypertension
Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension 1 2 1 Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Clarification: Women adequately treated for hypertension are at lower risk for acute myocardial infarction and stroke than are untreated women. Although no data exist, POC users with adequately controlled and monitored hypertension should be at lower risk for acute myocardial infarction and stroke than are untreated hypertensive POC users.
b. Elevated blood pressure levels
(properly taken measurements)
Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Evidence: Limited evidence suggests that among women with hypertension, those who used POPs or progestin-only injectables had a small increased risk for cardiovascular events compared with women who did not use these methods (75).
   i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg 1 2 1
   ii. Systolic =160 mm Hg or diastolic =100 mm Hg 2 3 2
c. Vascular disease 2 3 2 Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation.
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal) 1 1 1
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
   i. Higher risk for recurrent DVT/PE (one or more risk factors) 2 2 2
     • History of estrogen-associated DVT/PE
• Pregnancy-associated DVT/PE
• Idiopathic DVT/PE
• Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
   ii. Lower risk for recurrent DVT/PE (no risk factors) 2 2 2
b. Acute DVT/PE 2 2 2 Evidence: No direct evidence exists on use of POCs among women with acute DVT/PE. Although findings on the risk for venous thrombosis with use of POCs in otherwise healthy women is inconsistent, any small increased risk is substantially less than that with COCs (7577).
c. DVT/PE and established anticoagulant therapy for at least 3 months Evidence: No direct evidence exists on use of POCs among women with DVT/PE receiving anticoagulant therapy. Although findings on the risk for venous thrombosis with use of POCs is inconsistent in otherwise healthy women, any small increased risk is substantially less than that with COCs (7577).
Limited evidence indicates that intramuscular injections of DMPA in women receiving chronic anticoagulation therapy does not pose a significant risk for hematoma at the injection site or increase the risk for heavy or irregular vaginal bleeding (78).
   i. Higher risk for recurrent DVT/PE (one or more risk factors) 2 2 2
      • Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
   ii. Lower risk for recurrent DVT/PE (no risk factors) 2 2 2
d. Family history (first-degree relatives) 1 1 1
e. Major surgery
   i. With prolonged immobilization 2 2 2
   ii. Without prolonged immobilization 1 1 1
f. Minor surgery without immobilization 1 1 1
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; and protein S, protein C, and antithrombin deficiencies)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
2 2 2 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
Superficial venous disorders
a. Varicose veins 1 1 1
b. Superficial venous thrombosis (acute or history) 1 1 1
Current and history of ischemic heart disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation Initiation Continuation Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation.
2 3 3 2 3
Stroke (history of cerebrovascular accident)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation Initiation Continuation Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. However, little concern exists about these effects with regard to POPs. The effects of DMPA might persist for some time after discontinuation.
2 3 3 2 3
Valvular heart disease
Complicated valvular heart disease is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 1 1 1
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis) 1 1 1
Peripartum cardiomyopathy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Evidence: No direct evidence exists on the safety of POCs among women with peripartum cardiomyopathy. Limited indirect evidence from noncomparative studies of women with cardiac disease demonstrated few cases of hypertension, thromboembolism, and heart failure in women with cardiac disease using POPs and DMPA (79).
Comment: Progestin-only implants might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (80)
   i. <6 months 1 1 1
   ii. =6 months 1 1 1
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (80) 2 2 2
Rheumatic Diseases
Systemic lupus erythematosus
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Initiation Continuation
a. Positive (or unknown) antiphospholipid antibodies 3 3 3 3 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (8199).
Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (100,101).
b. Severe thrombocytopenia 2 3 2 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (8199).
Comment: Severe thrombocytopenia increases the risk for bleeding. POCs might be useful in treating menorrhagia in women with severe thrombocytopenia. However, given the increased or erratic bleeding that might be seen on initiation of DMPA and its irreversibility for 11–13 weeks after administration, initiation of this method in women with severe thrombocytopenia should be done with caution.
c. Immunosuppressive therapy 2 2 2 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (8199).
d. None of the above 2 2 2 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (8199).
Rheumatoid arthritis
a. Receiving immunosuppressive therapy 1 2/3 1 Clarification (DMPA): DMPA use among women receiving long-term corticosteroid therapy with a history of, or with risk factors for, nontraumatic fractures is classified as category 3. Otherwise, DMPA use for women with rheumatoid arthritis is classified as category 2.
Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (102).
b. Not receiving immunosuppressive therapy 1 2 1 Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (102).
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe) 1 1 1
b. Migraine Evidence: No studies directly examined the risk for stroke among women with migraine using POCs (103). Limited evidence demonstrated that women using POPs, DMPA, or implants do not have an increased risk for ischemic stroke compared with nonusers (104).
Comment: Menstrual migraine is a subtype of migraine without aura. For more information, see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf).
    i. Without aura (This category of migraine includes menstrual migraine.) 1 1 1
   ii. With aura 1 1 1
Epilepsy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 Clarification: If a woman is taking anticonvulsants, see Drug Interactions section. Certain anticonvulsants lower POC effectiveness.
Multiple sclerosis Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with multiple sclerosis does not worsen the clinical course of disease (105).
Comment: Women with multiple sclerosis might have compromised bone health from disease-related disability, immobility, and use of corticosteroids. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
a. With prolonged immobility 1 2 1
b. Without prolonged immobility 1 2 1
Depressive Disorders
Depressive disorders 1 1 1 Clarification: If a woman is taking psychotropic medications or St. John’s wort, see Drug Interactions section.
Evidence: The frequency of psychiatric hospitalizations for women with bipolar disorder or depression did not significantly differ among women using DMPA, LNG-IUD, Cu-IUD, or sterilization (106).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy bleeding 2 2 2 Comment: Irregular menstrual bleeding patterns are common among healthy women. POC use frequently induces an irregular bleeding pattern. Implant use might induce irregular bleeding patterns, especially during the first 3–6 months, although these patterns might persist longer.
b. Heavy or prolonged bleeding (includes regular and irregular patterns) 2 2 2 Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition.
Unexplained vaginal bleeding
(suspicious for serious condition) before evaluation
3 3 2 Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation.
Comment: POCs might cause irregular bleeding patterns, which might mask symptoms of underlying pathologic conditions. The effects of DMPA might persist for some time after discontinuation.
Endometriosis 1 1 1
Benign ovarian tumors (including cysts) 1 1 1
Severe dysmenorrhea 1 1 1
Gestational trophoblastic disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
a. Suspected gestational trophoblastic disease (immediate postevacuation)
   i. Uterine size first trimester 1 1 1
   ii. Uterine size second trimester 1 1 1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)
   i. Undetectable/nonpregnant ß–hCG levels 1 1 1
   ii. Decreasing ß–hCG levels 1 1 1
   iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease 1 1 1
   iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease 1 1 1
Cervical ectropion 1 1 1
Cervical intraepithelial neoplasia 2 2 1 Evidence: Among women with persistent human papillomavirus infection, long-term DMPA use (=5 years) might increase the risk for carcinoma in situ and invasive carcinoma (107).
Cervical cancer
(awaiting treatment)
2 2 1 Comment: Theoretical concern exists that POC use might affect prognosis of the existing disease. While awaiting treatment, women may use POCs. In general, treatment of this condition can render a woman sterile.
Breast disease
Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass 2 2 2 Clarification: Evaluation should be pursued as early as possible.
b. Benign breast disease 1 1 1
c. Family history of cancer 1 1 1
d. Breast cancer Comment: Breast cancer is a hormonally sensitive tumor, and the prognosis for women with current or recent breast cancer might worsen with POC use.
   i. Current 4 4 4
   ii. Past and no evidence of current disease for 5 years 3 3 3
Endometrial hyperplasia 1 1 1
Endometrial cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 Comment: While awaiting treatment, women may use POCs. In general, treatment of this condition renders a woman sterile.
Ovarian cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 Comment: While awaiting treatment, women may use POCs. In general, treatment of this condition can render a woman sterile.
Uterine fibroids 1 1 1 Comment: POCs do not appear to cause growth of uterine fibroids.
Pelvic inflammatory disease Comment: Whether POCs, like COCs, reduce the risk for PID among women with STDs is unknown; however, they do not protect against HIV or lower genital tract STDs.
a. Past PID
    i. With subsequent pregnancy 1 1 1
    ii. Without subsequent pregnancy 1 1 1
b. Current PID 1 1 1
Sexually transmitted diseases
a. Current purulent cervicitis or chlamydial infection or gonococcal infection 1 1 1
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) 1 1 1
c. Other factors related to STDs 1 1 1
HIV
High risk for HIV 1 1 1 Clarification (DMPA): Some studies suggest that women using progestin-only injectable contraception might be at increased risk for HIV acquisition; other studies do not show this association. CDC reviewed all available evidence and agreed that the data were not sufficiently conclusive to change current guidance. However, because of the inconclusive nature of the body of evidence on possible increased risk for HIV acquisition, women using progestin-only injectable contraception should be strongly advised to also always use condoms (male or female) and take other HIV preventive measures. Expansion of contraceptive method mix and further research on the relationship between hormonal contraception and HIV infection are essential. These recommendations will be continually reviewed in light of new evidence.
Evidence: Overall, evidence does not support an association between oral contraceptives and risk for HIV acquisition, evidence is inconsistent regarding an association between DMPA and increased risk for HIV acquisition, and no studies have suggested an increased risk for HIV acquisition with etonogestrel implants although data are limited (108).
HIV infection
For women with HIV infection who are not clinically well or not using ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 Clarification: Drug interactions might exist between hormonal contraceptives and ARV drugs; see Drug Interactions section.
Evidence: Overall, evidence does not support an association between POC use and progression of HIV. Limited direct evidence on an association between POC use and transmission of HIV to noninfected partners, as well as studies measuring genital viral shedding as a proxy for infectivity, have had mixed results. Studies measuring whether hormonal contraceptive methods affect plasma HIV viral load generally have found no effect (109111).
Other Infections
Schistosomiasis
Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 1 1 1 Evidence: Among women with uncomplicated schistosomiasis, limited evidence showed that DMPA use had no adverse effects on liver function (112).
b. Fibrosis of the liver (if severe, see Cirrhosis section) 1 1 1
Tuberculosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Clarification: If a woman is taking rifampin, see Drug Interactions section. Rifampin is likely to decrease the effectiveness of some POCs.
a. Nonpelvic 1 1 1
b. Pelvic 1 1 1
Malaria 1 1 1
Endocrine Conditions
Diabetes
Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease 1 1 1 Evidence: POCs had no adverse effects on serum lipid levels in women with a history of gestational diabetes in two small studies (113,114). Limited evidence is inconsistent about the development of noninsulin-dependent diabetes among users of POCs with a history of gestational diabetes (115118).
b. Nonvascular disease Evidence: Among women with insulin-dependent or non–insulin-dependent diabetes, limited evidence on use of POCs (POPs, DMPA, and LNG implant) suggests that these methods have little effect on short-term or long-term diabetes control (e.g., glycosylated hemoglobin levels), hemostatic markers, or lipid profile (119122).
   i. Non-insulin dependent 2 2 2
   ii. Insulin dependent 2 2 2
c. Nephropathy, retinopathy or
neuropathy
2 3 2 Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. The effects of DMPA might persist for some time after discontinuation. Some POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs.
d. Other vascular disease or diabetes of >20 years’ duration 2 3 2 Comment: Concern exists about hypoestrogenic effects and reduced HDL levels, particularly among users of DMPA. The effects of DMPA might persist for some time after discontinuation. Some POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs.
Thyroid disorders
a. Simple goiter 1 1 1
b. Hyperthyroid 1 1 1
c. Hypothyroid 1 1 1
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease) 1 2 2 Evidence: Risk for disease relapse among women with IBD using oral contraceptives (most studies did not specify formulation) did not increase significantly from that for nonusers (123).
Comment: Absorption of POPs among women with IBD might be reduced if the woman has substantial malabsorption caused by severe disease or small bowel surgery.
Women with IBD have a higher prevalence of osteoporosis and osteopenia than the general population. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
Gallbladder disease
a. Symptomatic
   i. Treated by cholecystectomy 2 2 2
   ii. Medically treated 2 2 2
   iii. Current 2 2 2
b. Asymptomatic 2 2 2
History of cholestasis
a. Pregnancy related 1 1 1
b. Past COC related 2 2 2 Comment: Theoretical concern exists that a history of COC-related cholestasis might predict subsequent cholestasis with POC use. However, this has not been documented.
Viral hepatitis
a. Acute or flare 1 1 1
b. Carrier 1 1 1
c. Chronic 1 1 1
Cirrhosis
Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated) 1 1 1
b. Severe (decompensated) 3 3 3
Liver tumors
Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
  i. Focal nodular hyperplasia 2 2 2 Evidence: Limited direct evidence suggests that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (124).
  ii. Hepatocellular adenoma 3 3 3 Comment: No evidence is available about hormonal contraceptive use among women with hepatocellular adenoma. COC use in healthy women is associated with development and growth of hepatocellular adenoma; whether other hormonal contraceptives have similar effects is not known.
b. Malignant (hepatoma) 3 3 3
Respiratory Conditions
Cystic fibrosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 1 Clarification: Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
Clarification: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives.
Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with cystic fibrosis is not associated with worsening of disease severity. Very limited evidence suggests that cystic fibrosis does not impair the effectiveness of hormonal contraception (125).
Comment: Women with cystic fibrosis have a higher prevalence of osteopenia, osteoporosis, and fragility fractures than the general population. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
Anemias
Thalassemia 1 1 1
Sickle cell disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 Evidence: Among women with sickle cell disease, POC use did not have adverse effects on hematologic parameters and, in some studies, was beneficial with respect to clinical symptoms (126133).
Iron deficiency anemia 1 1 1 Comment: Changes in the menstrual pattern associated with POC use have little effect on hemoglobin levels.
Solid Organ Transplantation
Solid organ transplantation
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy 2 2 2
b. Uncomplicated 2 2 2
Drug Interactions
Antiretroviral therapy Comment: These recommendations generally are for ARV agents used alone. However, most women receiving ARV therapy are using multiple drugs in combination. In general, whether interactions between ARVs and hormonal contraceptives differ when ARVs are given alone or in combination is unknown.
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
  i. Abacavir (ABC) 1 1 1 Evidence: NRTIs do not appear to have significant risk for interactions with hormonal contraceptive methods (134139).
  ii. Tenofovir (TDF) 1 1 1
  iii. Zidovudine (AZT) 1 1 1
  iv. Lamivudine (3TC) 1 1 1
  v. Didanosine (DDI) 1 1 1
  vi. Emtricitabine (FTC) 1 1 1
  vii. Stavudine (D4T) 1 1 1
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
  i. Efavirenz (EFV) 2 1 2 Clarification: Evidence suggests drug interactions between EFV and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
Evidence: One study found that women using etonogestrel implants with EFV had a higher pregnancy rate than women not using ARVs, although confidence intervals overlapped and absolute pregnancy rates were still lower than for other hormonal methods; another study found that etonogestrel levels were decreased and 5% of women had presumptive ovulation while using etonogestrel implants with EFV (140,141). Three studies of women using LNG implants showed increased pregnancy rates for women using EFV-containing ARV therapy compared with no ARV use, although absolute pregnancy rates were still lower than for other hormonal methods in one study (141143); another study of LNG implant users found no difference in pregnancy rates with EFV compared with no EFV (144).No significant effects were found on pregnancy rates, DMPA levels, EFV levels, or HIV disease progression in women using DMPA and EFV compared with DMPA alone (141,144148). No significant effects were found on HIV disease progression in women using LNG implants and EFV compared with no ARVs (143). No data have assessed effectiveness of contraceptive implants during later years of use when progestin concentrations are lower and risk for failure from drug interactions might be greater.
  ii. Etravirine (ETR) 1 1 1
  iii. Nevirapine (NVP) 1 1 1 Evidence: Five studies found no significant increase in pregnancy rates among women using implants and NVP compared with implants alone (141144,149). Four studies found no significant increase in pregnancy rates among women using DMPA or other contraceptive injectables and NVP compared with DMPA or other contraceptive injectables alone (141,144,147,150). One study found no ovulations or changes in DMPA concentrations (145). No effect was found on HIV disease progression with use of NVP and DMPA or LNG implants (143,145,147149,151). No data have assessed effectiveness of contraceptive implants during later years of use when progestin concentrations are lower and risk for failure from drug interactions might be greater.
  iv. Rilpivirine (RPV) 1 1 1
c. Ritonavir-boosted protease inhibitors
  i. Ritonavir-boosted atazanavir (ATV/r) 2 1 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
Evidence: One pharmacokinetic study demonstrated increased progestin concentrations with use of POPs and ATV/r compared with POPs alone (152).
  ii. Ritonavir-boosted darunavir (DRV/r) 2 1 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
  iii. Ritonavir-boosted fosamprenavir (FPV/r) 2 1 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
  iv. Ritonavir-boosted lopinavir (LPV/r) 1 1 1 Evidence: One study demonstrated no pregnancies, no ovulations, no change in LPV/r level, and no change in HIV disease progression in women using DMPA (153); another study found a small increase in pregnancy rate in women using DMPA with LPV/r compared with no ARV therapy, however confidence intervals overlapped (141). Two studies found no increased risk for pregnancy in women using implants (141,142). Two studies found contraceptive hormones increased in women using LPV/r with DMPA or etonogestrel implants (140,153).
  v. Ritonavir-boosted saquinavir (SQV/r) 2 1 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
  vi. Ritonavir-boosted tipranavir (TPV/r) 2 1 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.
d. Protease inhibitors without ritonavir
  i. Atazanavir (ATV) 1 1 1 Comment: When ATV is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels might vary when combined with other ARVs.
  ii. Fosamprenavir (FPV) 2 2 2 Clarification: Theoretical concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the ARV drug. The drug interaction likely involves CYP3A4 pathways; POCs have less effect on CYP3A4 enzymes than CHCs.
  iii. Indinavir (IDV) 1 1 1
  iv. Nelfinavir (NFV) 2 1 2 Clarification: Theoretically, drug interactions might occur between certain protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive. Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA. Concern exists that interactions between NFV and POCs might decrease NFV levels.
Evidence: One study found no pregnancies, no ovulations, no change in DMPA concentrations and no change in HIV disease progression with use of DMPA and NFV compared with DMPA alone; NFV concentrations were decreased with concomitant DMPA use (145,147).
e. CCR5 co-receptor antagonists
  i. Maraviroc (MVC) 1 1 1
f. HIV integrase strand transfer inhibitors
  i. Raltegravir (RAL) 1 1 1
  ii. Dolutegravir (DTG) 1 1 1
  iii. Elvitegravir (EVG) 1 1 1 Comment: When EVG is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.
g. Fusion inhibitors
  i. Enfuvirtide 1 1 1
Anticonvulsant therapy
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine) 2 1 3 Clarification: Although the interaction of certain anticonvulsants with POPs and etonogestrel implants is not harmful to women, it is likely to reduce the effectiveness of POPs and etonogestrel implants. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is a category 1 because its effectiveness is not decreased by use of certain anticonvulsants.
Evidence: Use of certain anticonvulsants might decrease the effectiveness of POCs (154156).
b. Lamotrigine 1 1 1 Evidence: No drug interactions have been reported among women with epilepsy receiving lamotrigine and POCs (157).
Antimicrobial therapy
a. Broad-spectrum antibiotics 1 1 1
b. Antifungals 1 1 1
c. Antiparasitics 1 1 1
d. Rifampin or rifabutin therapy 2 1 3 Clarification: Although the interaction of rifampin or rifabutin with POPs and etonogestrel implants is not harmful to women, it is likely to reduce the effectiveness of POPs and etonogestrel implants. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is a category 1 because its effectiveness is not decreased by use of rifampin or rifabutin. Whether increasing the hormone dose of POPs alleviates this concern remains unclear.
Psychotropic medications Comment: For many common psychotropic agents, limited or no theoretical concern exits for clinically significant drug interactions when co-administered with hormonal contraceptives. However, either no or very limited data exist examining potential interactions for these classes of medications.
a. SSRIs 1 1 1 Evidence: No evidence specifically examined the use of POCs with SSRIs. Limited clinical and pharmacokinetic data do not demonstrate concern for SSRIs decreasing the effectiveness of oral contraceptives. Limited evidence suggests that for women taking SSRIs, the use of hormonal contraceptives was not associated with differences in effectiveness of the SSRI for treatment or in adverse events when compared with women not taking hormonal contraceptives (158).
Comment: Drugs that are inhibitors of CYP3A4 or CYP2C9 theoretically have the potential to increase levels of contraceptive steroid, which might increase adverse events. Fluvoxamine is an SSRI known to be a moderate inhibitor of both 3A4 and 2C9; however, no clinical or pharmacokinetic studies were identified to explore potential drug-drug interactions.
St. John’s wort 2 1 2 Evidence: No evidence specifically examined the use of POCs with St John’s wort. Although clinical data are limited, studies with pharmacokinetic and pharmacodynamics outcomes raise concern that St. John’s wort might decrease effectiveness of hormonal contraceptives, including increased risk for breakthrough bleeding and ovulation and increased metabolism of estrogen and progestin. Any interactions might be dependent on the dose of St John’s wort, and the concentration of active ingredients across types of St. John’s wort preparations may vary (159).
Comment: Any potential effect on contraceptive effectiveness is likely to be lower with DMPA than with other POCs because of the higher dose of DMPA.

Abbreviations: ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; COC = combined oral contraceptive; DMPA = depot medroxyprogesterone acetate; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; LDL = low-density lipoprotein; LNG = levonorgestrel; NA = not applicable; NET-EN = norethisterone enantate; PE = pulmonary embolism; PID = pelvic inflammatory disease; POC = progestin-only contraceptive; POP = progestin-only pill; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted disease; VTE = venous thromboembolism.

References

  1. Lanza LL, McQuay LJ, Rothman KJ, et al. Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture. Obstet Gynecol 2013;121:593–600. CrossRef PubMed
  2. Harel Z, Riggs S, Vaz R, Flanagan P, Harel D, Machan JT. Bone accretion in adolescents using the combined estrogen and progestin transdermal contraceptive method Ortho Evra: a pilot study. J Pediatr Adolesc Gynecol 2010;23:23–31. CrossRef PubMed
  3. Kaunitz AM, Miller PD, Rice VM, Ross D, McClung MR. Bone mineral density in women aged 25–35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation. Contraception 2006;74:90–9. CrossRef PubMed
  4. Kaunitz AM, Arias R, McClung M. Bone density recovery after depot medroxyprogesterone acetate injectable contraception use. Contraception 2008;77:67–76. CrossRef PubMed
  5. Kaunitz AM, Darney PD, Ross D, Wolter KD, Speroff L. Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density. Contraception 2009;80:7–17. CrossRef PubMed
  6. Lappe JM, Stegman MR, Recker RR. The impact of lifestyle factors on stress fractures in female Army recruits. Osteoporos Int 2001;12:35–42. CrossRef PubMed
  7. Lara-Torre E, Edwards CP, Perlman S, Hertweck SP. Bone mineral density in adolescent females using depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol 2004;17:17–21. CrossRef PubMed
  8. Lopez LM, Chen M, Mullins S, Curtis KM, Helmerhorst FM. Steroidal contraceptives and bone fractures in women: evidence from observational studies. Cochrane Database Syst Rev 2012;8:CD009849. PubMed
  9. Lopez LM, Grimes DA, Schulz KF, Curtis KM. Steroidal contraceptives: effect on bone fractures in women. Cochrane Database Syst Rev 2011;(7):CD006033. PubMed
  10. Meier C, Brauchli YB, Jick SS, Kraenzlin ME, Meier CR. Use of depot medroxyprogesterone acetate and fracture risk. J Clin Endocrinol Metab 2010;95:4909–16. CrossRef PubMed
  11. Merki-Feld GS, Neff M, Keller PJ. A 2-year prospective study on the effects of depot medroxyprogesterone acetate on bone mass-response to estrogen and calcium therapy in individual users. Contraception 2003;67:79–86. CrossRef PubMed
  12. Monteiro-Dantas C, Espejo-Arce X, Lui-Filho JF, Fernandes AM, Monteiro I, Bahamondes L. A three-year longitudinal evaluation of the forearm bone density of users of etonogestrel- and levonorgestrel-releasing contraceptive implants. Reprod Health 2007;4:11. CrossRef PubMed
  13. Naessen T, Olsson SE, Gudmundson J. Differential effects on bone density of progestogen-only methods for contraception in premenopausal women. Contraception 1995;52:35–9. CrossRef PubMed
  14. Sanches L, Marchi NM, Castro S, Juliato CT, Villarroel M, Bahamondes L. Forearm bone mineral density in postmenopausal former users of depot medroxyprogesterone acetate. Contraception 2008;78:365–9. CrossRef PubMed
  15. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology 2002;13:581–7. CrossRef PubMed
  16. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch Pediatr Adolesc Med 2005;159:139–44. CrossRef PubMed
  17. Segall-Gutierrez P, Agarwal R, Ge M, Lopez C, Hernandez G, Stanczyk FZ. A pilot study examining short-term changes in bone mineral density among class 3 obese users of depot-medroxyprogesterone acetate. Eur J Contracept Reprod Health Care 2013;18:199–205. CrossRef PubMed
  18. Tang OS, Tang G, Yip PS, Li B. Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study. Contraception 2000;62:161–4. CrossRef PubMed
  19. Vestergaard P, Rejnmark L, Mosekilde L. The effects of depot medroxyprogesterone acetate and intrauterine device use on fracture risk in Danish women. Contraception 2008;78:459–64. CrossRef PubMed
  20. Viola AS, Castro S, Marchi NM, Bahamondes MV, Viola CF, Bahamondes L. Long-term assessment of forearm bone mineral density in postmenopausal former users of depot medroxyprogesterone acetate. Contraception 2011;84:122–7. CrossRef PubMed
  21. Walsh JS, Eastell R, Peel NF. Depot medroxyprogesterone acetate use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density. Fertil Steril 2010;93:697–701. CrossRef PubMed
  22. Wetmore CM, Ichikawa L, LaCroix AZ, Ott SM, Scholes D. Association between caffeine intake and bone mass among young women: potential effect modification by depot medroxyprogesterone acetate use. Osteoporos Int 2008;19:519–27. CrossRef PubMed
  23. Wong AY, Tang LC, Chin RK. Levonorgestrel-releasing intrauterine system (Mirena) and depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: a randomised controlled trial. Aust N Z J Obstet Gynaecol 2010;50:273–9. CrossRef PubMed
  24. Yang KY, Kim YS, Ji YI, Jung MH. Changes in bone mineral density of users of the levonorgestrel-releasing intrauterine system. J Nippon Med Sch 2012;79:190–4. CrossRef PubMed
  25. Zhang MH, Zhang W, Zhang AD, Yang Y, Gai L. Effect of depot medroxyprogesterone acetate on bone mineral density in adolescent women. Chin Med J (Engl) 2013;126:4043–7. PubMed
  26. Bahamondes MV, Monteiro I, Castro S, Espejo-Arce X, Bahamondes L. Prospective study of the forearm bone mineral density of long-term users of the levonorgestrel-releasing intrauterine system. Hum Reprod 2010;25:1158–64. CrossRef PubMed
  27. Banks E, Berrington A, Casabonne D. Overview of the relationship between use of progestogen-only contraceptives and bone mineral density. BJOG 2001;108:1214–21. CrossRef PubMed
  28. Beerthuizen R, van Beek A, Massai R, Mäkäräinen L, Hout J, Bennink HC. Bone mineral density during long-term use of the progestagen contraceptive implant Implanon compared to a non-hormonal method of contraception. Hum Reprod 2000;15:118–22. CrossRef PubMed
  29. Beksinska ME, Kleinschmidt I, Smit JA, Farley TM. Bone mineral density in adolescents using norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives for contraception. Contraception 2007;75:438–43. CrossRef PubMed
  30. Beksinska ME, Kleinschmidt I, Smit JA, Farley TM. Bone mineral density in a cohort of adolescents during use of norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives and after discontinuation of norethisterone enanthate. Contraception 2009;79:345–9. CrossRef PubMed
  31. Berenson AB, Breitkopf CR, Grady JJ, Rickert VI, Thomas A. Effects of hormonal contraception on bone mineral density after 24 months of use. Obstet Gynecol 2004;103:899–906. CrossRef PubMed
  32. Berenson AB, Rahman M, Breitkopf CR, Bi LX. Effects of depot medroxyprogesterone acetate and 20-microgram oral contraceptives on bone mineral density. Obstet Gynecol 2008;112:788–99. CrossRef PubMed
  33. Busen NH, Britt RB, Rianon N. Bone mineral density in a cohort of adolescent women using depot medroxyprogesterone acetate for one to two years. J Adolesc Health 2003;32:257–9. CrossRef PubMed
  34. Caird LE, Reid-Thomas V, Hannan WJ, Gow S, Glasier AF. Oral progestogen-only contraception may protect against loss of bone mass in breast-feeding women. Clin Endocrinol (Oxf) 1994;41:739–45. CrossRef PubMed
  35. Clark MK, Sowers M, Levy B, Nichols S. Bone mineral density loss and recovery during 48 months in first-time users of depot medroxyprogesterone acetate. Fertil Steril 2006;86:1466–74. CrossRef PubMed
  36. Cromer BA, Lazebnik R, Rome E, et al. Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception. Am J Obstet Gynecol 2005;192:42–7. CrossRef PubMed
  37. Cromer BA, Blair JM, Mahan JD, Zibners L, Naumovski Z. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr 1996;129:671–6. CrossRef PubMed
  38. Cromer BA, Bonny AE, Stager M, et al. Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. Fertil Steril 2008;90:2060–7. CrossRef PubMed
  39. Cromer BA, Stager M, Bonny A, et al. Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls. J Adolesc Health 2004;35:434–41. CrossRef PubMed
  40. Cundy T, Ames R, Horne A, et al. A randomized controlled trial of estrogen replacement therapy in long-term users of depot medroxyprogesterone acetate. J Clin Endocrinol Metab 2003;88:78–81. CrossRef PubMed
  41. Cundy T, Cornish J, Evans MC, Roberts H, Reid IR. Recovery of bone density in women who stop using medroxyprogesterone acetate. BMJ 1994;308:247–8. CrossRef PubMed
  42. Cundy T, Cornish J, Roberts H, Reid IR. Menopausal bone loss in long-term users of depot medroxyprogesterone acetate contraception. Am J Obstet Gynecol 2002;186:978–83. CrossRef PubMed
  43. Di X, Li Y, Zhang C, Jiang J, Gu S. Effects of levonorgestrel-releasing subdermal contraceptive implants on bone density and bone metabolism. Contraception 1999;60:161–6. CrossRef PubMed
  44. Díaz S, Reyes MV, Zepeda A, et al. Norplant® implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod 1999;14:2499–505. CrossRef PubMed
  45. Gai L, Zhang J, Zhang H, Gai P, Zhou L, Liu Y. The effect of depot medroxyprogesterone acetate (DMPA) on bone mineral density (BMD) and evaluating changes in BMD after discontinuation of DMPA in Chinese women of reproductive age. Contraception 2011;83:218–22. CrossRef PubMed
  46. Bahamondes L, Espejo-Arce X, Hidalgo MM, Hidalgo-Regina C, Teatin-Juliato C, Petta CA. A cross-sectional study of the forearm bone density of long-term users of levonorgestrel-releasing intrauterine system. Hum Reprod 2006;21:1316–9. CrossRef PubMed
  47. Bahamondes L, Monteiro-Dantas C, Espejo-Arce X, et al. A prospective study of the forearm bone density of users of etonorgestrel- and levonorgestrel-releasing contraceptive implants. Hum Reprod 2006;21:466–70. CrossRef PubMed
  48. Pitts SA, Feldman HA, Dorale A, Gordon CM. Bone mineral density, fracture, and vitamin D in adolescents and young women using depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol 2012;25:23–6. CrossRef PubMed
  49. US Department of Health and Human Services. Healthy people 2020: maternal, infant, and child health objectives. Washington, DC: US Department of Health and Human Services; 2015. http://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health/objectives
  50. Braga GC, Ferriolli E, Quintana SM, Ferriani RA, Pfrimer K, Vieira CS. Immediate postpartum initiation of etonogestrel-releasing implant: a randomized controlled trial on breastfeeding impact. Contraception 2015;92:536–42. CrossRef PubMed
  51. Phillips SJ, Tepper NK, Kapp N, Nanda K, Temmerman M, Curtis KM. Progestogen-only contraceptive use among breastfeeding women: a systematic review. Contraception 2015;S0010-7824(15)00585-5. PubMed
  52. Kurunmäki H. Contraception with levonorgestrel-releasing subdermal capsules, Norplant, after pregnancy termination. Contraception 1983;27:473–82. CrossRef PubMed
  53. Kurunmäki H, Toivonen J, Lähteenmäki PL, Luukkainen T. Immediate postabortal contraception with Norplant: levonorgestrel, gonadotropin, estradiol, and progesterone levels over two postabortal months and return of fertility after removal of Norplant capsules. Contraception 1984;30:431–42. . CrossRef PubMed
  54. Lähteenmäki P, Toivonen J, Lähteenmäki PL. Postabortal contraception with norethisterone enanthate injections. Contraception 1983;27:553–62 CrossRef PubMed
  55. Ortayli N, Bulut A, Sahin T, Sivin I. Immediate postabortal contraception with the levonorgestrel intrauterine device, Norplant, and traditional methods. Contraception 2001;63:309–14. CrossRef PubMed
  56. Beksinska ME, Smit JA, Kleinschmidt I, Milford C, Farley TM. Prospective study of weight change in new adolescent users of DMPA, NET-EN, COCs, nonusers and discontinuers of hormonal contraception. Contraception 2010;81:30–4. CrossRef PubMed
  57. Bender NM, Segall-Gutierrez P, Najera SO, Stanczyk FZ, Montoro M, Mishell DR . Effects of progestin-only long-acting contraception on metabolic markers in obese women. Contraception 2013;88:418–25. CrossRef PubMed
  58. Berenson AB, Rahman M. Changes in weight, total fat, percent body fat, and central-to-peripheral fat ratio associated with injectable and oral contraceptive use. Am J Obstet Gynecol 2009;200:329.e1–8. CrossRef PubMed
  59. Bonny AE, Secic M, Cromer B. Early weight gain related to later weight gain in adolescents on depot medroxyprogesterone acetate. Obstet Gynecol 2011;117:793–7. . CrossRef PubMed
  60. Bonny AE, Ziegler J, Harvey R, Debanne SM, Secic M, Cromer BA. Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method. Arch Pediatr Adolesc Med 2006;160:40–5 CrossRef PubMed
  61. Clark MK, Dillon JS, Sowers M, Nichols S. Weight, fat mass, and central distribution of fat increase when women use depot-medroxyprogesterone acetate for contraception. Int J Obes 2005;29:1252–8. CrossRef PubMed
  62. Gerlach LS, Saldaña SN, Wang Y, Nick TG, Spigarelli MG. Retrospective review of the relationship between weight change and demographic factors following initial depot medroxyprogesterone acetate injection in adolescents. Clin Ther 2011;33:182–7. CrossRef PubMed
  63. Jain J, Jakimiuk AJ, Bode FR, Ross D, Kaunitz AM. Contraceptive efficacy and safety of DMPA-SC. Contraception 2004;70:269–75. CrossRef PubMed
  64. Kozlowski KJ, Rickert VI, Hendon A, Davis P. Adolescents and Norplant: preliminary findings of side effects. J Adolesc Health 1995;16:373–8. CrossRef PubMed
  65. Le YC, Rahman M, Berenson AB. Early weight gain predicting later weight gain among depot medroxyprogesterone acetate users. Obstet Gynecol 2009;114:279–84. CrossRef PubMed
  66. Leiman G. Depo-medroxyprogesterone acetate as a contraceptive agent: its effect on weight and blood pressure. Am J Obstet Gynecol 1972;114:97–102. . CrossRef PubMed
  67. Lopez LM, Grimes DA, Chen M, et al. Hormonal contraceptives for contraception in overweight or obese women. Cochrane Database Syst Rev 2013;4:CD008452. PubMed
  68. Mangan SA, Larsen PG, Hudson S. Overweight teens at increased risk for weight gain while using depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol 2002;15:79–82. CrossRef PubMed
  69. Nyirati CM, Habash DL, Shaffer LE. Weight and body fat changes in postpartum depot-medroxyprogesterone acetate users. Contraception 2013;88:169–76. CrossRef PubMed
  70. Pantoja M, Medeiros T, Baccarin MC, Morais SS, Bahamondes L, Fernandes AM. Variations in body mass index of users of depot-medroxyprogesterone acetate as a contraceptive. Contraception 2010;81:107–11. CrossRef PubMed
  71. Risser WL, Gefter LR, Barratt MS, Risser JM. Weight change in adolescents who used hormonal contraception. J Adolesc Health 1999;24:433–6. CrossRef PubMed
  72. Segall-Gutierrez P, Xiang AH, Watanabe RM, et al. Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use. Contraception 2012;85:36–41. CrossRef PubMed
  73. Westhoff C, Jain JK, Milsom I, Ray A. Changes in weight with depot medroxyprogesterone acetate subcutaneous injection 104 mg/0.65 mL. Contraception 2007;75:261–7. CrossRef PubMed
  74. Paulen ME, Zapata LB, Cansino C, Curtis KM, Jamieson DJ. Contraceptive use among women with a history of bariatric surgery: a systematic review. Contraception 2010;82:86–94. CrossRef PubMed
  75. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. Contraception 1998;57:315–24 CrossRef PubMed
  76. Heinemann LA, Assmann A, DoMinh T, Garbe E. Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Eur J Contracept Reprod Health Care 1999;4:67–73. CrossRef PubMed
  77. Vasilakis C, Jick H, del Mar Melero-Montes M. Risk of idiopathic venous thromboembolism in users of progestagens alone. Lancet 1999;354:1610–1. CrossRef PubMed
  78. Sönmezer M, Atabekoglu C, Cengiz B, Dökmeci F, Cengiz SD. Depot-medroxyprogesterone acetate in anticoagulated patients with previous hemorrhagic corpus luteum. Eur J Contracept Reprod Health Care 2005;10:9–14. CrossRef PubMed
  79. Tepper NK, Paulen ME, Marchbanks PA, Curtis KM. Safety of contraceptive use among women with peripartum cardiomyopathy: a systematic review. Contraception 2010;82:95–101. CrossRef PubMed
  80. The Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Little, Brown and Co; 1994.
  81. Bernatsky S, Clarke A, Ramsey-Goldman R, et al. Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus. Rheumatology (Oxford) 2004;43:1178–81. CrossRef PubMed
  82. Bernatsky S, Ramsey-Goldman R, Gordon C, et al. Factors associated with abnormal Pap results in systemic lupus erythematosus. Rheumatology (Oxford) 2004;43:1386–9. CrossRef PubMed
  83. Chopra N, Koren S, Greer WL, et al. Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol 2002;29:1683–8. PubMed
  84. Esdaile JM, Abrahamowicz M, Grodzicky T, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2001;44:2331–7. CrossRef PubMed
  85. Julkunen HA. Oral contraceptives in systemic lupus erythematosus: side-effects and influence on the activity of SLE. Scand J Rheumatol 1991;20:427–33. CrossRef PubMed
  86. Julkunen HA, Kaaja R, Friman C. Contraceptive practice in women with systemic lupus erythematosus. Br J Rheumatol 1993;32:227–30. CrossRef PubMed
  87. Jungers P, Dougados M, Pélissier C, et al. Influence of oral contraceptive therapy on the activity of systemic lupus erythematosus. Arthritis Rheum 1982;25:618–23. CrossRef PubMed
  88. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 1997;145:408–15. CrossRef PubMed
  89. McAlindon T, Giannotta L, Taub N, D’Cruz D, Hughes G. Environmental factors predicting nephritis in systemic lupus erythematosus. Ann Rheum Dis 1993;52:720–4. CrossRef PubMed
  90. McDonald J, Stewart J, Urowitz MB, Gladman DD. Peripheral vascular disease in patients with systemic lupus erythematosus. Ann Rheum Dis 1992;51:56–60. CrossRef PubMed
  91. Mintz G, Gutiérrez G, Delezé M, Rodríguez E. Contraception with progestagens in systemic lupus erythematosus. Contraception 1984;30:29–38. CrossRef PubMed
  92. Petri M. Musculoskeletal complications of systemic lupus erythematosus in the Hopkins Lupus Cohort: an update. Arthritis Care Res 1995;8:137–45. CrossRef PubMed
  93. Petri M. Lupus in Baltimore: evidence-based ‘clinical pearls’ from the Hopkins Lupus Cohort. Lupus 2005;14:970–3. CrossRef PubMed
  94. Petri M, Kim MY, Kalunian KC, et al. ; OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005;353:2550–8. CrossRef PubMed
  95. Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005;353:2539–49. CrossRef PubMed
  96. Sarabi ZS, Chang E, Bobba R, et al. Incidence rates of arterial and venous thrombosis after diagnosis of systemic lupus erythematosus. Arthritis Rheum 2005;53:609–12. CrossRef PubMed
  97. Schaedel ZE, Dolan G, Powell MC. The use of the levonorgestrel-releasing intrauterine system in the management of menorrhagia in women with hemostatic disorders. Am J Obstet Gynecol 2005;193:1361–3. CrossRef PubMed
  98. Somers E, Magder LS, Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol 2002;29:2531–6. PubMed
  99. Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 1976;60:221–5. CrossRef PubMed
  100. Choojitarom K, Verasertniyom O, Totemchokchyakarn K, Nantiruj K, Sumethkul V, Janwityanujit S. Lupus nephritis and Raynaud’s phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies. Clin Rheumatol 2008;27:345–51. CrossRef PubMed
  101. Wahl DG, Guillemin F, de Maistre E, Perret C, Lecompte T, Thibaut G. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus—a meta-analysis. Lupus 1997;6:467–73. CrossRef PubMed
  102. Farr SL, Folger SG, Paulen ME, Curtis KM. Safety of contraceptive methods for women with rheumatoid arthritis: a systematic review. Contraception 2010;82:64–71. CrossRef PubMed
  103. Tepper N, Whiteman M, Zapata L, Marchbanks P, Curtis K. Safety of hormonal contraceptives among women with migraine: a systematic review. Contraception 2016. Epub May 3, 2016. . CrossRef
  104. Tepper NK, Whiteman MK, Marchbanks PA, James AH, Curtis KM. Progestin-only contraception and thromboembolism: a systematic review. Contraception 2016. Epub May 3, 2016. CrossRef PubMed
  105. Zapata LB, Oduyebo T, Whiteman MK, Marchbanks PA, Curtis KM. Contraceptive use among women with multiple sclerosis: a systematic review. Contraception . In press 2016.
  106. Pagano HP, Zapata LB, Berry-Bibee E, Nanda K, Curtis KM. Safety of hormonal contraception and intrauterine devices among women with depressive and bipolar disorders: a systematic review. Contraception 2016. Epub June 27, 2016. CrossRef
  107. Smith JS, Green J, Berrington de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003;361:1159–67. . CrossRef PubMed
  108. Polis CB, Phillips SJ, Curtis KM, et al. Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence. Contraception 2014;90:360–90 CrossRef PubMed
  109. Phillips SJ, Curtis KM, Polis CB. Effect of hormonal contraceptive methods on HIV disease progression: a systematic review. AIDS 2013;27:787–94. CrossRef PubMed
  110. Polis CB, Phillips SJ, Curtis KM. Hormonal contraceptive use and female-to-male HIV transmission: a systematic review of the epidemiologic evidence. AIDS 2013;27:493–505. CrossRef PubMed
  111. Phillips SJ, Polis CB, Curtis KM. The safety of hormonal contraceptives for women living with HIV and their sexual partners. Contraception 2016;93:11–6 . CrossRef PubMed
  112. Tagy AH, Saker ME, Moussa AA, Kolgah A. The effect of low-dose combined oral contraceptive pills versus injectable contraceptive (Depot Provera) on liver function tests of women with compensated bilharzial liver fibrosis. Contraception 2001;64:173–6. CrossRef PubMed
  113. Pyörälä T, Vähäpassi J, Huhtala M. The effect of lynestrenol and norethindrone on the carbohydrate and lipid metabolism in subjects with gestational diabetes. Ann Chir Gynaecol 1979;68:69–74. PubMed
  114. R&aringdberg T, Gustafson A, Skryten A, Karlsson K. Metabolic studies in gestational diabetic women during contraceptive treatment: effects on glucose tolerance and fatty acid composition of serum lipids. Gynecol Obstet Invest 1982;13:17–29. CrossRef PubMed
  115. Kjos SL, Peters RK, Xiang A, Thomas D, Schaefer U, Buchanan TA. Contraception and the risk of type 2 diabetes mellitus in Latina women with prior gestational diabetes mellitus. JAMA 1998;280:533–8. CrossRef PubMed
  116. Nelson AL, Le MH, Musherraf Z, Vanberckelaer A. Intermediate-term glucose tolerance in women with a history of gestational diabetes: natural history and potential associations with breastfeeding and contraception. Am J Obstet Gynecol 2008;198:699.e1–8.
  117. Xiang AH, Kawakubo M, Buchanan TA, Kjos SL. A longitudinal study of lipids and blood pressure in relation to method of contraception in Latino women with prior gestational diabetes mellitus. Diabetes Care 2007;30:1952–8. CrossRef PubMed
  118. Xiang AH, Kawakubo M, Kjos SL, Buchanan TA. Long-acting injectable progestin contraception and risk of type 2 diabetes in Latino women with prior gestational diabetes mellitus. Diabetes Care 2006;29:613–7. CrossRef PubMed
  119. Diab KM, Zaki MM. Contraception in diabetic women: comparative metabolic study of Norplant, depot medroxyprogesterone acetate, low dose oral contraceptive pill and CuT380A. J Obstet Gynaecol Res 2000;26:17–26. CrossRef PubMed
  120. Lunt H, Brown LJ. Self-reported changes in capillary glucose and insulin requirements during the menstrual cycle. Diabet Med 1996;13:525–30. CrossRef PubMed
  121. R&aringdberg T, Gustafson A, Skryten A, Karlsson K. Oral contraception in diabetic women. A cross-over study on serum and high density lipoprotein (HDL) lipids and diabetes control during progestogen and combined estrogen/progestogen contraception. Horm Metab Res 1982;14:61–5. PubMed
  122. Skouby SO, Mølsted-Pedersen L, Kühl C, Bennet P. Oral contraceptives in diabetic women: metabolic effects of four compounds with different estrogen/progestogen profiles. Fertil Steril 1986;46:858–64 . CrossRef PubMed
  123. Zapata LB, Paulen ME, Cansino C, Marchbanks PA, Curtis KM. Contraceptive use among women with inflammatory bowel disease: a systematic review. Contraception 2010;82:72–85. CrossRef PubMed
  124. Kapp N, Curtis KM. Hormonal contraceptive use among women with liver tumors: a systematic review. Contraception 2009;80:387–90. CrossRef PubMed
  125. Whiteman MK, Oduyebo T, Zapata LB, Walker S, Curtis KM. Contraceptive safety among women with cystic fibrosis: a systematic review. Contraception 2016. Epub June 7, 2016. CrossRef
  126. Adadevoh BK, Isaacs WA. The effect of megestrol acetate on sickling. Am J Med Sci 1973;265:367–70. CrossRef PubMed
  127. Barbosa IC, Ladipo OA, Nascimento ML, et al. Carbohydrate metabolism in sickle cell patients using a subdermal implant containing nomegestrol acetate (Uniplant). Contraception 2001;63:263–5. CrossRef PubMed
  128. de Abood M, de Castillo Z, Guerrero F, Espino M, Austin KL. Effect of Depo-Provera or Microgynon on the painful crises of sickle cell anemia patients. Contraception 1997;56:313–6. CrossRef PubMed
  129. De Ceulaer K, Hayes R, Gruber C, Serjeant GR. Medroxyprogesterone acetate and homozygous sickle-cell disease. Lancet 1982;320:229–31. CrossRef PubMed
  130. Howard RJ, Lillis C, Tuck SM. Contraceptives, counselling, and pregnancy in women with sickle cell disease. BMJ 1993;306:1735–7. CrossRef PubMed
  131. Ladipo OA, Falusi AG, Feldblum PJ, Osotimehin BO, Otolorin EO, Ojengbede OA. Norplant use by women with sickle cell disease. Int J Gynaecol Obstet 1993;41:85–7. CrossRef PubMed
  132. Nascimento ML, Ladipo OA, Coutinho EM. Nomegestrol acetate contraceptive implant use by women with sickle cell disease. Clin Pharmacol Ther 1998;64:433–8. CrossRef PubMed
  133. Yoong WC, Tuck SM, Yardumian A. Red cell deformability in oral contraceptive pill users with sickle cell anaemia. Br J Haematol 1999;104:868–70. CrossRef PubMed
  134. Aweeka FT, Rosenkranz SL, Segal Y, et al. NIAID AIDS Clinical Trials Group. The impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine. AIDS 2006;20:1833–41. CrossRef PubMed
  135. Kearney BP, Mathias A. Lack of effect of tenofovir disoproxil fumarate on pharmacokinetics of hormonal contraceptives. Pharmacotherapy 2009;29:924–9. CrossRef PubMed
  136. Todd CS, Deese J, Wang M, et al. FEM-PrEP Study Group. Sino-implant (II)® continuation and effect of concomitant tenofovir disoproxil fumarate-emtricitabine use on plasma levonorgestrel concentrations among women in Bondo, Kenya. Contraception 2015;91:248–52. CrossRef PubMed
  137. Murnane PM, Heffron R, Ronald A, et al. Partners PrEP Study Team. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception. AIDS 2014;28:1825–30. CrossRef PubMed
  138. Kasonde M, Niska RW, Rose C, et al. Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana. PLoS One 2014;9:e90111. CrossRef PubMed
  139. Callahan R, Nanda K, Kapiga S, et al. FEM-PrEP Study Group. Pregnancy and contraceptive use among women participating in the FEM-PrEP trial. J Acquir Immune Defic Syndr 2015;68:196–203. CrossRef PubMed
  140. Vieira CS, Bahamondes MV, de Souza RM, et al. Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women. J Acquir Immune Defic Syndr 2014;66:378–85. CrossRef PubMed
  141. Patel RC, Onono M, Gandhi M, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV 2015;2:e474–82. CrossRef PubMed
  142. Perry SH, Swamy P, Preidis GA, Mwanyumba A, Motsa N, Sarero HN. Implementing the Jadelle implant for women living with HIV in a resource-limited setting: concerns for drug interactions leading to unintended pregnancies. AIDS 2014;28:791–3. CrossRef PubMed
  143. Scarsi KK, Darin KM, Nakalema S, et al. Unintended pregnancies observed with combined use of the levonorgestrel contraceptive implant and efavirenz-based antiretroviral therapy: a three-arm pharmacokinetic evaluation over 48 weeks. Clin Infect Dis 2015;62:675–82. CrossRef PubMed
  144. Pyra M, Heffron R, Mugo NR, et al. Partners in Prevention HSVHIV Transmission Study and Partners PrEP Study Teams. Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy. AIDS 2015;29:2353–9. CrossRef PubMed
  145. Cohn SE, Park JG, Watts DH, et al. ACTG A5093 Protocol Team. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions. Clin Pharmacol Ther 2007;81:222–7. CrossRef PubMed
  146. Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril 2008;90:965–71. CrossRef PubMed
  147. Watts DH, Park JG, Cohn SE, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception 2008;77:84–90. CrossRef PubMed
  148. Polis CB, Nakigozi G, Ssempijja V, et al. Effect of injectable contraceptive use on response to antiretroviral therapy among women in Rakai, Uganda. Contraception 2012;86:725–30. CrossRef PubMed
  149. Hubacher D, Liku J, Kiarie J, et al. Effect of concurrent use of anti-retroviral therapy and levonorgestrel sub-dermal implant for contraception on CD4 counts: a prospective cohort study in Kenya. J Int AIDS Soc 2013;16:18448. CrossRef PubMed
  150. Myer L, Carter RJ, Katyal M, Toro P, El-Sadr WM, Abrams EJ. Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study. PLoS Med 2010;7:e1000229. CrossRef PubMed
  151. Day S, Graham SM, Masese LN, et al. A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy. J Acquir Immune Defic Syndr 2014;66:452–6. CrossRef PubMed
  152. DuBois BN, Atrio J, Stanczyk FZ, Cherala G. Increased exposure of norethindrone in HIV+ women treated with ritonavir-boosted atazanavir therapy. Contraception 2015;91:71–5. CrossRef PubMed
  153. Luque AE, Cohn SE, Park JG, et al. Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study. Antimicrob Agents Chemother 2015;59:2094–101. CrossRef PubMed
  154. Odlind V, Olsson SE. Enhanced metabolism of levonorgestrel during phenytoin treatment in a woman with Norplant implants. Contraception 1986;33:257–61. CrossRef PubMed
  155. Schindlbeck C, Janni W, Friese K. Failure of Implanon contraception in a patient taking carbamazepin for epilepsia. Arch Gynecol Obstet 2006;273:255–6. CrossRef PubMed
  156. Shane-McWhorter L, Cerveny JD, MacFarlane LL, Osborn C. Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy. Pharmacotherapy 1998;18:1360–4. PubMed
  157. Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia 2005;46:1414–7. CrossRef PubMed
  158. Berry-Bibee E, Kim MJ, Simmons K, Pagano P, Curtis K. Drug interactions between hormonal contraceptives and psychotropic drugs: a systematic review. Contraception. In press 2016.
  159. Berry-Bibee E, Kim MJ, Tepper N, Riley H, Curtis K. The safety of St. John’s wort and hormonal contraceptives: a systematic review. Contraception. In press 2016.

Appendix D

Classifications for Combined Hormonal Contraceptives

Combined hormonal contraceptives (CHCs) include low-dose (containing =35 µg ethinyl estradiol) combined oral contraceptives (COCs), the combined hormonal patch, and the combined vaginal ring ( Box D1) ( Table D1). Limited information is available about the safety of the combined hormonal patch and combined vaginal ring among women with specific medical conditions. Evidence indicates that the combined hormonal patch and the combined vaginal ring provide comparable safety and pharmacokinetic profiles to COCs with similar hormone formulations (133). Pending further studies, the evidence available for recommendations about COCs applies to the recommendations for the combined hormonal patch and vaginal ring. Therefore, the patch and ring should have the same categories as COCs, except where noted. Therefore, the assigned categories should be considered a preliminary best judgement, which will be reevaluated as new data become available.

COCs, the patch, and the ring do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited

Return to your place in the textBOX D1. Categories for classifying combined hormonal contraceptives

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE D1. Classifications for combined hormonal contraceptives, including pill, patch, and ring
Condition Category CHCs Clarifications/Evidence/Comments
Personal Characteristics and Reproductive History
Pregnancy NA Clarification: Use of CHCs is not required. No known harm to the woman, the course of her pregnancy, or the fetus occurs if CHCs are inadvertently used during pregnancy.
Age Evidence: Evidence is inconsistent about whether CHC use affects fracture risk (3445), although three recent studies show no effect (34,35,45). CHC use might decrease BMD in adolescents, especially in those choosing very low-dose formulations (COCs containing <30 µg ethinyl estradiol) (4659). CHC use has little to no effect on BMD in premenopausal women (6074) and might preserve bone mass in those who are perimenopausal (7583). BMD is a surrogate marker for fracture risk that might not be valid for premenopausal women and therefore might not accurately predict current or future (postmenopausal) fracture risk (8486).
Comment: The risk for cardiovascular disease increases with age and might increase with CHC use. In the absence of other adverse clinical conditions, CHCs can be used until menopause.
a. Menarche to <40 years 1
b. =40 years 2
Parity
a. Nulliparous 1
b. Parous 1
Breastfeeding
a. <21 days postpartum 4 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
b. 21 to <30 days postpartum
  i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 3 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
  ii. Without other risk factors for VTE 3 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
c. 30–42 days postpartum
   i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 3 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
  ii. Without other risk factors for VTE 2 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
d. >42 days postpartum 2 Clarification: Breastfeeding provides important health benefits for mother and infant. The U.S. Department of Health and Human Services recommends increasing the proportion of infants initially breastfed, exclusively breastfed through 6 months of life, and continuing breastfeeding through at least 1 year of life as key public health goals (87).
Evidence: Clinical studies demonstrate conflicting results regarding effects on breastfeeding continuation or exclusivity in women exposed to COCs during lactation. No consistent effects on infant growth or illness have been reported. Adverse health outcomes or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been demonstrated; however, studies have been inadequately designed to determine whether a risk for either serious or subtle long-term effects exists (88).
Comment: Certain women might be at risk for breastfeeding difficulties, such as women with previous breastfeeding difficulties, certain medical conditions, or certain perinatal complications, and those who deliver preterm. For these women, as for all women, discussions about contraception for breastfeeding women should include information about risks, benefits, and alternatives.
Postpartum (nonbreastfeeding women)
a. <21 days postpartum 4 Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094). Risk for pregnancy during the first 21 days postpartum is very low but increases after that point; ovulation before first menses is common (95).
b. 21–42 days postpartum
  i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2 postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 3 Clarification: For women with other risk factors for VTE, these risk factors might increase the classification to a category 4.
Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
  ii. Without other risk factors for VTE 2 Evidence: One study examined use of CHCs during the postpartum period and found that VTE rates were higher for CHC users compared with nonusers at all time points postpartum (89). Rates were significantly different only after 13 weeks postpartum; however, the numbers needed to harm were lowest in the first 6 weeks postpartum. VTE risk is increased during pregnancy and the postpartum period; this risk is most pronounced in the first 3 weeks after delivery, decreasing to near baseline levels by 42 days postpartum (9094).
c. >42 days postpartum 1
Postabortion Clarification: CHCs may be started immediately postabortion.
Evidence: Women who started taking COCs immediately after first trimester medical or surgical abortion did not experience more side effects or adverse vaginal bleeding outcomes or clinically significant changes in coagulation parameters than did women who used a placebo, an IUD, a nonhormonal contraceptive method, or delayed COC initiation (96102). Limited evidence on women using the ring immediately after first trimester medical or surgical abortion found no serious adverse events and no infection related to use of the combined vaginal ring during 3 cycles of follow-up postabortion (103).
a. First trimester 1
b. Second trimester 1
c. Immediate postseptic abortion 1
Past ectopic pregnancy 1 Comment: The risk for future ectopic pregnancy is increased among women who have had an ectopic pregnancy in the past. CHCs protect against pregnancy in general, including ectopic gestation.
History of pelvic surgery 1
Smoking Evidence: COC users who smoked were at increased risk for cardiovascular diseases, especially myocardial infarction, compared with those who did not smoke. Studies also showed an increased risk for myocardial infarction with increasing number of cigarettes smoked per day (104116).
a. Age <35 years 2
b. Age =35 years
  i. <15 cigarettes per day 3
  ii. =15 cigarettes per day 4
Obesity Evidence: Obese women who use COCs are more likely than obese women who do not use COCs to experience VTE. Research examining the interaction between COCs and BMI on VTE risk is limited, particularly for women in the highest BMI categories (BMI =35 kg/m2). Although the absolute risk for VTE in otherwise healthy women of reproductive age is small, obese women are at 2–3 times higher risk for VTE than normal weight women regardless of COC use. Limited evidence suggests that obese women who use COCs do not have a higher risk for acute myocardial infarction or stroke than do obese nonusers (117). Limited evidence suggests that effectiveness of some COC formulations might decrease with increasing BMI, however the observed reductions in effectiveness are minimal and evidence is conflicting (118125). Effectiveness of the patch might be reduced in women >90 kg (126). Limited evidence suggests obese women are no more likely to gain weight during COC or vaginal ring use than normal weight or overweight women (117,127).
a. BMI =30 kg/m2 2
b. Menarche to <18 years and BMI =30 kg/m2 2
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent laparoscopic placement of an adjustable gastric band (128).
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) COCs: 3
Patch and ring: 1
Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives among women who underwent a biliopancreatic diversion; however, evidence from pharmacokinetic studies reported conflicting results of oral contraceptive effectiveness among women who underwent a jejunoileal bypass (128).
Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to decrease oral contraceptive effectiveness, perhaps further decreased by postoperative complications, such as long-term diarrhea or vomiting.
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels) 3/4 Clarification: When a woman has multiple major risk factors, any of which alone would substantially increase her risk for cardiovascular disease, use of CHCs might increase her risk to an unacceptable level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two category 2 risk factors might not necessarily warrant a higher category.
Clarification: The recommendations apply to known preexisting medical conditions or characteristics. Few if any screening tests are needed before initiation of contraception. See the U.S. Selected Practice Recommendations for Contraceptive Use (http://www.cdc.gov/reproductivehealth/unintendedpregnancy/usspr.htm).
Hypertension
Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension 3 Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Clarification: Women adequately treated for hypertension are at reduced risk for acute myocardial infarction and stroke compared with untreated women. Although no data exist, CHC users with adequately controlled and monitored hypertension should be at reduced risk for acute myocardial infarction and stroke compared with untreated hypertensive CHC users.
Evidence: Among women with hypertension, COC users were at higher risk than nonusers for stroke, acute myocardial infarction, and peripheral arterial disease (104,106,113116,129143). Discontinuation of COCs in women with hypertension might improve blood pressure control (144).
b. Elevated blood pressure levels
(properly taken measurements)
Clarification: For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist, risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
Evidence: Among women with hypertension, COC users were at higher risk than nonusers for stroke, acute myocardial infarction, and peripheral arterial disease (104,106,113116,129143). Discontinuation of COCs in women with hypertension might improve blood pressure control (144).
  i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg 3
  ii. Systolic =160 mm Hg or diastolic =100 mm Hg 4
c. Vascular disease 4
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal) 2 Evidence: Women with a history of high blood pressure in pregnancy who also used COCs had a higher risk for myocardial infarction and VTE than did COC users who did not have a history of high blood pressure during pregnancy. The absolute risks for acute myocardial infarction and VTE in this population remained small (115,130,142,143,145151).
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
  i. Higher risk for recurrent DVT/PE (one or more risk factors) 4
     • History of estrogen-associated DVT/PE
• Pregnancy-associated DVT/PE
• Idiopathic DVT/PE
• Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
  ii. Lower risk for recurrent DVT/PE (no risk factors) 3
b. Acute DVT/PE 4
c. DVT/PE and established anticoagulant therapy for at least 3 months Clarification: Women using anticoagulant therapy are at risk for gynecologic complications of therapy, such as hemorrhagic ovarian cysts and severe menorrhagia. Hormonal contraceptive methods can be of benefit in preventing or treating these complications. When a contraceptive method is used as a therapy, rather than solely to prevent pregnancy, the risk/benefit ratio might differ and should be considered on a case-by-case basis.
  i. Higher risk for recurrent DVT/PE (one or more risk factors) 4
     • Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DTV/PE
  ii. Lower risk for recurrent DVT/PE (no risk factors) 3
d. Family history (first-degree relatives) 2 Comment: Some conditions that increase the risk for DTV/PE are heritable.
e. Major surgery
  i. With prolonged immobilization 4
  ii. Without prolonged immobilization 2
f. Minor surgery without immobilization 1
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; and protein S, protein C, and antithrombin deficiencies)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
4 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
Evidence: Among women with thrombogenic mutations, COC users had a twofold to twentyfold higher risk for thrombosis than did nonusers (152175).
Superficial venous disorders
a. Varicose veins 1 Evidence: One study suggested that among women with varicose veins, the rate of VTE and superficial venous thrombosis was higher in oral contraceptive users compared with nonusers; however, statistical significance was not reported and the number of events was small (176).
b. Superficial venous thrombosis (acute or history) 3 Clarification: Superficial venous thrombosis might be associated with an increased risk for VTE. If a woman has risk factors for concurrent DVT (e.g., known thrombophilia or cancer) or has current or history of DVT, see recommendations for DVT/PE. Superficial venous thrombosis associated with a peripheral intravenous catheter is less likely to be associated with additional thrombosis and use of CHCs may be considered.
Evidence: One study demonstrated that among women with superficial venous thrombosis, the risk for VTE was higher in oral contraceptive users compared with nonusers (176).
Current and history of ischemic heart disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
4
Stroke (history of cerebrovascular accident)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
4
Valvular heart disease
Complicated valvular heart disease is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 2
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis) 4 Comment: Among women with valvular heart disease, CHC use may further increase the risk for arterial thrombosis; women with complicated valvular heart disease are at greatest risk.
Peripartum cardiomyopathy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Evidence: No direct evidence exists about the safety of CHCs among women with peripartum cardiomyopathy. Limited indirect evidence from noncomparative studies of women with cardiac disease demonstrated few cases of hypertension and transient ischemic attack in women with cardiac disease using COCs. No cases of heart failure were reported (177).
Comment: COCs might increase fluid retention in healthy women; fluid retention may worsen heart failure in women with peripartum cardiomyopathy. COCs might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (178)
  i. <6 months 4
  ii. =6 months 3
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (178) 4
Rheumatic Diseases
Systemic lupus erythematosus
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Positive (or unknown) antiphospholipid antibodies 4 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179197).
Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous thrombosis (198,199).
b. Severe thrombocytopenia 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179197).
c. Immunosuppressive therapy 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179197).
d. None of the above 2 Clarification: Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in U.S. MEC should be the same for women with SLE who have these conditions. For all subconditions of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors. Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (179197).
Rheumatoid arthritis Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthritis with use of oral contraceptives, progesterone, or estrogen (200).
a. Receiving immunosuppressive therapy 2
b. Not receiving immunosuppressive therapy 2
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe) 1 Clarification: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf). Any new headaches or marked changes in headaches should be evaluated.
b. Migraine Clarification: Classification depends on accurate diagnosis of those severe headaches that are migraines and those headaches that are not, as well as diagnosis of ever experiencing aura. Aura is a specific focal neurologic symptom. For more information about headache classification see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf). Any new headaches or marked changes in headaches should be evaluated.
Clarification: Classification is for women without any other risk factors for stroke (e.g., age, hypertension, and smoking).
Evidence: Among women with migraine, oral contraceptive use is associated with about a threefold increased risk for ischemic stroke compared with nonuse, although most studies did not specify migraine type or oral contraceptive formulation. The only study to examine migraine type found that the risk for ischemic stroke among women with migraine with aura was increased to a similar level among both oral contraceptive users and nonusers, compared with women without migraine (201). The risk for ischemic stroke is increased among women using COCs, compared with women not using COCs (104,202). The risk for ischemic stroke is also increased among women with migraine with aura, compared with women without migraine (203205). One older meta-analysis found that migraine without aura was associated with an increased risk for ischemic stroke, while two more recent meta-analyses did not find such an association (203205).
Comment: Menstrual migraine is a subtype of migraine without aura. For more information, see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf).
  i. Without aura (This category of migraine includes menstrual migraine.) 2
  ii. With aura 4
Epilepsy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 Clarification: If a woman is taking anticonvulsants, see Drug Interactions section. Certain anticonvulsants lower COC effectiveness. The extent to which patch or ring use is similar to COC use in this regard remains unclear.
Multiple sclerosis Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with multiple sclerosis does not worsen the clinical course of disease (206).
Comment: No data exist that evaluate the increased risk for VTE among women with multiple sclerosis using CHCs. However, women with multiple sclerosis are at higher risk than unaffected women for VTE.
a. With prolonged immobility 3
b. Without prolonged immobility 1
Depressive Disorders
Depressive disorders 1 Clarification: If a woman is receiving psychotropic medications or St. John’s wort, see Drug Interactions section.
Evidence: COC use was not associated with increased depressive symptoms in women with depression or scoring above threshold levels on a validated depression screening instrument compared with baseline or with nonusers with depression. One small study of women with bipolar disorder found that oral contraceptives did not significantly change mood across the menstrual cycle (207).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy bleeding 1 Comment: Irregular menstrual bleeding patterns are common among healthy women.
b. Heavy or prolonged bleeding (includes regular and irregular patterns) 1 Clarification: Unusually heavy bleeding should raise the suspicion of a serious underlying condition.
Evidence: A Cochrane Collaboration Review identified one randomized controlled trial evaluating the effectiveness of COC use compared with naproxen and danazol in treating menorrhagia. Women with menorrhagia did not report worsening of the condition or any adverse events related to COC use (208).
Unexplained vaginal bleeding
(suspicious for serious condition) before evaluation
2 Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation.
Comment: No conditions that cause vaginal bleeding will be worsened in the short-term by use of CHCs.
Endometriosis 1 Evidence: A Cochrane Collaboration Review identified one randomized controlled trial evaluating the effectiveness of COC use compared with a gonadotropin-releasing hormone analog in treating the symptoms of endometriosis. Women with endometriosis did not report worsening of the condition or any adverse events related to COC use (209).
Benign ovarian tumors (including cysts) 1
Severe dysmenorrhea 1 Evidence: Risk for side effects with COC use was not higher among women with dysmenorrhea than among women not using COCs. Some COC users had a reduction in pain and bleeding (210,211).
Gestational trophoblastic disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Clarification: For all subconditions of gestational trophoblastic disease, classifications are based on the assumption that women are under close medical supervision because of the need for monitoring of ß-hCG levels for appropriate disease surveillance.
Evidence: After molar pregnancy evacuation, the balance of evidence found COC use did not increase the risk for postmolar trophoblastic disease, and ß–hCG levels regressed more rapidly in some COC users than in nonusers (212). Limited evidence suggests that use of COCs during chemotherapy does not significantly affect the regression or treatment of postmolar trophoblastic disease compared with women who used a nonhormonal contraceptive method or DMPA during chemotherapy (212).
a. Suspected gestational trophoblastic disease (immediate postevacuation)
  i. Uterine size first trimester 1
  ii. Uterine size second trimester 1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)
  i. Undetectable/nonpregnant ß-hCG levels 1
  ii. Decreasing ß-hCG levels 1
  iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease 1
  iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease 1
Cervical ectropion 1 Comment: Cervical ectropion is not a risk factor for cervical cancer, and restriction of CHC use is unnecessary.
Cervical intraepithelial neoplasia 2 Evidence: Among women with persistent human papillomavirus infection, long-term COC use (=5 years) might increase the risk for carcinoma in situ and invasive carcinoma (213). Limited evidence on women with low-grade squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition (9).
Cervical cancer (awaiting treatment) 2 Comment: Theoretical concern exists that CHC use might affect prognosis of the existing disease. While awaiting treatment, women may use CHCs. In general, treatment of this condition can render a woman sterile.
Breast disease
Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass 2 Clarification: The woman should be evaluated as early as possible.
b. Benign breast disease 1
c. Family history of cancer 1 Evidence: Women with breast cancer susceptibility genes (e.g., BRCA1 and BRCA2) have a higher baseline risk for breast cancer than women without these genes. The baseline risk for breast cancer is also higher among women with a family history of breast cancer than among those who do not have such a history. However, evidence does not suggest that the increased risk for breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes is modified by the use of COCs (214231).
d. Breast cancer Comment: Breast cancer is a hormonally sensitive tumor, and the prognosis for women with current or recent breast cancer might worsen with CHC use.
  i. Current 4
  ii. Past and no evidence of current disease for 5 years 3
Endometrial hyperplasia 1
Endometrial cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 Comment: COC use reduces the risk for endometrial cancer; whether patch or ring use reduces the risk for endometrial cancer is not known. While awaiting treatment, women may use CHCs. In general, treatment of this condition renders a woman sterile.
Ovarian cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 Comment: COC use reduces the risk for ovarian cancer; whether patch or ring use reduces the risk for ovarian cancer is not known. While awaiting treatment, women may use CHCs. In general, treatment of this condition can render a woman sterile.
Uterine fibroids 1 Comment: COCs do not appear to cause growth of uterine fibroids, and patch and ring also are not expected to cause growth.
Pelvic inflammatory disease Comment: COCs might reduce the risk for PID among women with STDs but do not protect against HIV or lower genital tract STDs. Whether use of patch or ring reduces the risk for PID among women with STDs is unknown; however, they do not protect against HIV or lower genital tract STDs.
a. Past PID
  i. With subsequent pregnancy 1
  ii. Without subsequent pregnancy 1
b. Current PID 1
Sexually transmitted diseases
a. Current purulent cervicitis or chlamydial infection or gonococcal infection 1
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) 1
c. Other factors related to STDs 1
HIV
High risk for HIV 1 Evidence: Overall, evidence does not support an association between oral contraceptives and risk for HIV acquisition (232).
HIV infection
For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 Clarification: Drug interactions might exist between hormonal contraceptives and ARV drugs; see Drug Interactions section.
Evidence: Overall, evidence does not support an association between COC use and progression of HIV. Limited direct evidence does not support an association between COC use and transmission of HIV to noninfected partners; studies measuring genital viral shedding as a proxy for infectivity have had mixed results. Studies measuring whether hormonal contraceptive methods affect plasma HIV viral load generally have found no effect (233235).
Other Infections
Schistosomiasis
Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 1 Evidence: Among women with uncomplicated schistosomiasis, COC use had no adverse effects on liver function (236242).
b. Fibrosis of the liver (if severe, see Cirrhosis section) 1
Tuberculosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
Clarification: If a woman is taking rifampin, see Drug Interactions section. Rifampin is likely to decrease COC effectiveness. The extent to which patch or ring use is similar to COC use in this regard remains unclear.
a. Nonpelvic 1
b. Pelvic 1
Malaria 1
Endocrine Conditions
Diabetes
Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease 1 Evidence: The development of non–insulin-dependent diabetes in women with a history of gestational diabetes is not increased by use of COCs (243250). Likewise, lipid levels appear to be unaffected by COC use (251253).
b. Nonvascular disease Evidence: Among women with insulin-dependent or non–insulin-dependent diabetes, COC use had limited effect on daily insulin requirements and no effect on long-term diabetes control (e.g., glycosylated hemoglobin levels) or progression to retinopathy. Changes in lipid profile and hemostatic markers were limited, and most changes remained within normal values (254263).
  i. Non-insulin dependent 2
  ii. Insulin dependent 2
c. Nephropathy, retinopathy, or neuropathy 3/4 Clarification: The category should be assessed according to the severity of the condition.
d. Other vascular disease or diabetes of >20 years’ duration 3/4 Clarification: The category should be assessed according to the severity of the condition.
Thyroid disorders
a. Simple goiter 1
b. Hyperthyroid 1
c. Hypothyroid 1
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease) 2/3 Clarification: For women with mild IBD and with no other risk factor for VTE, the benefits of CHC use generally outweigh the risks (category 2). However, for women with IBD who are at increased risk for VTE (e.g., those with active or extensive disease, surgery, immobilization, corticosteroid use, vitamin deficiencies, or fluid depletion), the risks of CHC use generally outweigh the benefits (category 3).
Evidence: Risk for disease relapse was not significantly higher among women with IBD using oral contraceptives (most studies did not specify type) than among nonusers (264). Absorption of COCs among women with mild ulcerative colitis and no or small ileal resections was similar to the absorption among healthy women (264). Findings might not apply to women with Crohn’s disease or more extensive bowel resections. No data exist that evaluate the increased risk for VTE among women with IBD using CHCs. However, women with IBD are at higher risk than unaffected women for VTE (264).
Gallbladder disease Comment: CHCs might cause a small increased risk for gallbladder disease. CHCs might worsen existing gallbladder disease.
a. Symptomatic
  i. Treated by cholecystectomy 2
  ii. Medically treated 3
  iii. Current 3
b. Asymptomatic 2
History of cholestasis
a. Pregnancy related 2 Comment: History of pregnancy-related cholestasis might predict an increased risk for COC-related cholestasis.
b. Past COC related 3 Comment: History of COC-related cholestasis predicts an increased risk with subsequent COC use.
Viral hepatitis Initiation Continuation
a. Acute or flare 3/4 2 Clarification (initiation): The category should be assessed according to the severity of the condition.
Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma. For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction. Evidence is limited for COC use during active hepatitis (265).
b. Carrier 1 1 Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma. For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction. Evidence is limited for COC use during active hepatitis (265).
c. Chronic 1 1 Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or severity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma. For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction. Evidence is limited for COC use during active hepatitis (265).
Cirrhosis
Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated) 1
b. Severe (decompensated) 4
Liver tumors
Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
  i. Focal nodular hyperplasia 2 Evidence: Limited direct evidence suggests that hormonal contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular hyperplasia (266).
  ii. Hepatocellular adenoma 4
b. Malignant (hepatoma) 4
Respiratory Conditions
Cystic fibrosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 Clarification: Persons with cystic fibrosis are at increased risk for diabetes, liver disease, gallbladder disease, and VTE (particularly related to use of central venous catheters) and are frequently prescribed antibiotics. Categories assigned to such conditions in U.S. MEC should be the same for women with cystic fibrosis who have these conditions. For cystic fibrosis, classifications are based on the assumption that no other conditions are present; these classifications must be modified in the presence of such conditions.
Clarification: Certain drugs to treat cystic fibrosis (e.g., lumacaftor) might reduce effectiveness of hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives.
Evidence: Limited evidence suggests that use of COCs or oral contraceptives (type not specified) among women with cystic fibrosis is not associated with worsening of disease severity. Very limited evidence suggests that cystic fibrosis does not impair the effectiveness of hormonal contraception (267).
Anemias
Thalassemia 1 Comment: Anecdotal evidence from countries where thalassemia is prevalent indicates that COC use does not worsen the condition.
Sickle cell disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
2
Iron deficiency anemia 1 Comment: CHC use might decrease menstrual blood loss.
Solid Organ Transplantation
Solid organ transplantation
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft vasculopathy 4 Evidence: Limited evidence of COC and patch users indicated no overall changes in biochemical measures. However, one study reported discontinuations of COC use in two (8%) of 26 women as a result of serious medical complications, and in one case report, a woman developed cholestasis associated with high-dose COC use (268).
b. Uncomplicated 2 Clarification: Women with Budd-Chiari syndrome should not use CHCs because of the increased risk for thrombosis.
Evidence: Limited evidence of COC and patch users indicated no overall changes in biochemical measures. However, one study reported discontinuations of COC use in two (8%) of 26 women as a result of serious medical complications, and in one case report, a woman developed cholestasis associated with high-dose COC use (268).
Drug Interactions
Antiretroviral therapy Comment: These recommendations generally are for ARV agents used alone. However, most women receiving ARV therapy are using multiple drugs in combination. In general, whether interactions between ARVs and hormonal contraceptives differ when ARVs are given alone or in combination is unknown.
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
  i. Abacavir (ABC) 1 Evidence: NRTIs do not appear to have significant risk for interactions with hormonal contraceptive methods (269274).
  ii. Tenofovir (TDF) 1
  iii. Zidovudine (AZT) 1
  iv. Lamivudine (3TC) 1
  v. Didanosine (DDI) 1
  vi. Emtricitabine (FTC) 1
  vii. Stavudine (D4T) 1
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
  i. Efavirenz (EFV) 2 Clarification: Evidence suggests drug interactions between EFV and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
Evidence: Two studies suggested that pregnancy rates might be higher among women using COCs and EFV compared with COCs alone, although one study found no difference in pregnancy rates (275277) Two studies found conflicting results on ovulations in women receiving COCs and EFV compared with EFV alone (278,279). Two pharmacokinetic studies demonstrated decreases in ethinyl estradiol and progestin concentrations in women receiving COCs and EFV compared with COCs alone (279,280). Pharmacokinetic studies demonstrated generally no changes in EFV concentrations with concomitant COC use (279,280).
  ii. Etravirine (ETR) 1 Evidence: One study demonstrated no clinically relevant pharmacokinetic or pharmacodynamic changes in women using COCs and ETR compared with COCs alone (281).
  iii. Nevirapine (NVP) 1 Evidence: Five studies found no significant differences in pregnancy rates among women using COCs and NVP compared with women using COCs alone (275277,282,283). Three studies reported no ovulations among women receiving COCs and NVP (278,283,284). Two pharmacokinetic studies demonstrated decreased concentrations of ethinyl estradiol and progestin among women using COCs and NVP compared with COCs alone, and one study found no change in contraceptive hormone concentrations (278,284,285). Pharmacokinetic studies demonstrated generally no changes in NVP concentrations with concomitant COC use (278,285,286).
  iv. Rilpivirine (RPV) 1 Evidence: One study demonstrated no clinical significant pharmacokinetic changes or adverse events in women using COCs and RPV compared with COCs alone (287).
c. Ritonavir-boosted protease inhibitors
  i. Ritonavir-boosted atazanavir (ATV/r) 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
Evidence: One pharmacokinetic study demonstrated decreased estrogen but increased progestin concentrations in women using COCs and ATV/r compared with COCs alone (288).
  ii. Ritonavir-boosted darunavir (DRV/r) 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
Evidence: One pharmacokinetic study demonstrated no change in follicle-stimulating hormone or luteinizing hormone but decreases in ethinyl estradiol and norethindrone in women using COCs with DRV/r compared with COCs alone (289).
  iii. Ritonavir-boosted fosamprenavir (FPV/r) 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
Evidence: Information from the package label states that both ethinyl estradiol and norethindrone concentrations decreased with concurrent administration of COCs and FPV/r (290).
  iv. Ritonavir-boosted lopinavir (LPV/r) 1 Evidence: One study demonstrated a non-significant increase in pregnancy rates among women using COCs and LPV/r compared with COCs alone (275). One study demonstrated no ovulations in women using the combined hormonal patch and LPV/r compared with combined hormonal patch alone; ethinyl estradiol concentrations for COC and patch users decreased but norelgestromin concentrations increased with use of the patch (291).
  v. Ritonavir-boosted saquinavir (SQV/r) 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
Evidence: One pharmacokinetic study demonstrated no change in SQV concentrations in women using COC and SQV compared with COCs alone (292).
  iv. Ritonavir-boosted tipranavir (TPV/r) 2 Clarification: Theoretically, drug interactions might occur between certain ritonavir-boosted protease inhibitors and certain hormonal contraceptives that might reduce the effectiveness of the hormonal contraceptive.
Evidence: Information from the package label states that ethinyl estradiol concentrations decrease but norethindrone concentrations increased with concurrent administration of COCs and TPV/r (293).
d. Protease inhibitors without ritonavir
  i. Atazanavir (ATV) 2 Clarification: Theoretical concern exists that increased levels of ethinyl estradiol because of interactions with ATV might increase the risk for adverse events.
Evidence: Information from the package label states that there are inconsistent changes in ethinyl estradiol concentrations and increases in progestin concentrations with concurrent administration of two different COCs and ATV (294).
Comment: When ATV is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.
  ii. Fosamprenavir (FPV) 3 Clarification: Concern exists that interactions between FPV and hormonal contraceptives leading to decreased levels of FPV might diminish effectiveness of the ARV drug.
Evidence: Information from the package label states that amprenavir concentrations decreased with concurrent administration of COCs and amprenavir. Norethindrone concentrations increased and ethinyl estradiol concentrations did not change (290).
  iii. Indinavir (IDV) 1 Evidence: One small study found no pregnancies in women using COCs and IDV (277).
  iv. Nelfinavir (NFV) 2 Clarification: Evidence suggests drug interactions between certain protease inhibitors and certain hormonal contraceptives. These interactions might reduce the effectiveness of the hormonal contraceptive.
Evidence: One small study suggested that women using COCs and NFV may have had higher pregnancy rates than those using COCs alone (277).
e. CCR5 co-receptor antagonists
  i. Maraviroc (MVC) 1 Evidence: COC concentrations were not altered by co-administration with MVC (295).
f. HIV integrase strand transfer inhibitors
  i. Raltegravir (RAL) 1 Evidence: One pharmacokinetic study demonstrated increased concentrations of norgestimate and no change in ethinyl estradiol among women using COCs and RAL compared with COCs alone (296).
  ii. Dolutegravir (DTG) 1 Evidence: One study demonstrated no clinically relevant pharmacokinetic or pharmacodynamic changes in women using COCs and DTG compared with COCs alone (297).
  iii. Elvitegravir (EVG) 1 Evidence: Information from the package label states that ethinyl estradiol concentrations decreased and norgestimate concentrations increased with concurrent administration of COCs and EVG (298).
Comment: When ATV is administered with Cobicistat, theoretical concern exists for a drug interaction with hormonal contraceptives. Cobicistat is an inhibitor of CYP3A and CYP2D6 and could theoretically increase contraceptive hormone levels. However, its effects on CYP enzymes and drug levels may vary when combined with other ARVs.
g. Fusion inhibitors
  i. Enfuvirtide 1
Anticonvulsant therapy
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine) 3 Clarification: Although the interaction of certain anticonvulsants with CHCs is not harmful to women, it is likely to reduce the effectiveness of CHCs. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. When a COC is chosen, a preparation containing a minimum of 30 µg ethinyl estradiol should be used.
Evidence: Use of certain anticonvulsants might decrease the effectiveness of COCs (299302).
b. Lamotrigine 3 Clarification: The recommendation for lamotrigine applies only for situations where lamotrigine monotherapy is taken concurrently with COCs. Anticonvulsant treatment regimens that combine lamotrigine and non–enzyme-inducing antiepileptic drugs (e.g., sodium valproate) do not interact with COCs.
Evidence: Pharmacokinetic studies show levels of lamotrigine decrease significantly during COC use (303307). Some women who used both COCs and lamotrigine experienced increased seizure activity in one trial (303).
Antimicrobial therapy
a. Broad-spectrum antibiotics 1 Evidence: Most broad-spectrum antibiotics do not affect the contraceptive effectiveness of COCs (308344), patch (345), or ring (346).
b. Antifungals 1 Evidence: Studies of antifungal agents have shown no clinically significant pharmacokinetic interactions with COCs (347356), or ring (357).
c. Antiparasitics 1 Evidence: Studies of antiparasitic agents have shown no clinically significant pharmacokinetic interactions with COCs (236,358362).
d. Rifampin or rifabutin therapy 3 Clarification: Although the interaction of rifampin or rifabutin therapy with CHCs is not harmful to women, it is likely to reduce the effectiveness of CHCs. Use of other contraceptives should be encouraged for women who are long-term users of either of these drugs. When a COC is chosen, a preparation containing a minimum of 30 µg ethinyl estradiol should be used.
Evidence: The balance of the evidence suggests that rifampin reduces the effectiveness of COCs (363378). Data on rifabutin are limited, but effects on metabolism of COCs are less than with rifampin, and small studies have not shown evidence of ovulation (365,372).
Psychotropic medications Comment: For many common psychotropic agents, limited or no theoretical concern exists for clinically significant drug interactions when co-administered with hormonal contraceptives. However, either no or very limited data exist examining potential interactions for these classes of medications. For psychotropic agents that are CYP1A2 substrates, such as duloxetine, mirtazapine, ziprasidone, olanzapine, clomipramine, imipramine, and amitriptyline, co-administration with CHCs could theoretically yield increased concentrations of the psychotropic drug. For agents with narrow therapeutic windows, such as tricyclic antidepressants, increased drug concentrations might pose safety concerns that could necessitate closer monitoring.
a. SSRIs 1 Evidence: Limited clinical and pharmacokinetic data do not demonstrate concern for SSRIs decreasing the effectiveness of oral contraceptives. Limited evidence suggests that for women taking SSRIs, the use of hormonal contraceptives was not associated with differences in effectiveness of the SSRI for treatment or in adverse events when compared with women not taking hormonal contraceptives (379).
Comment: Drugs that are inhibitors of CYP3A4 or CYP2C9 theoretically have the potential to increase levels of contraceptive steroids which might increase adverse events. Fluvoxamine is an SSRI known to be a moderate inhibitor of both CYP3A4 and CYP2C9; however, no clinical or pharmacokinetic studies were identified to explore potential drug-drug interactions.
St. John’s wort 2 Evidence: Although clinical data are limited, studies with pharmacokinetic and pharmacodynamics outcomes raise concern that St. John’s wort might decrease effectiveness of hormonal contraceptives, including increased risk for breakthrough bleeding and ovulation and increased metabolism of estrogen and progestins. Any interactions might be dependent on the dose of St John’s wort, and the concentration of active ingredients across types of St. John’s wort preparations may vary (380).

Abbreviations: ARV = antiretroviral; BMD = bone mineral density; BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined oral contraceptive; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; IBD = inflammatory bowel disease; LDL = low-density lipoprotein; PE = pulmonary embolism; PID = pelvic inflammatory disease; SLE = systemic lupus erythematosus; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted infection; VTE = venous thromboembolism.

References

  1. Abrams LS, Skee DM, Natarajan J, Wong FA, Lasseter KC. Multiple-dose pharmacokinetics of a contraceptive patch in healthy women participants. Contraception 2001;64:287–94. CrossRef PubMed
  2. Ahrendt HJ, Nisand I, Bastianelli C, et al. Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. Contraception 2006;74:451–7. CrossRef PubMed
  3. Audet M-C, Moreau M, Koltun WD, et al. ORTHO EVRA/EVRA 004 Study Group. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial. JAMA 2001;285:2347–54. CrossRef PubMed
  4. Bjarnadóttir RI, Tuppurainen M, Killick SR. Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol. Am J Obstet Gynecol 2002;186:389–95. CrossRef PubMed
  5. Boonyarangkul A, Taneepanichskul S. Comparison of cycle control and side effects between transdermal contraceptive patch and an oral contraceptive in women older than 35 years. J Med Assoc Thai 2007;90:1715–9. PubMed
  6. Burkman RT. The transdermal contraceptive patch: a new approach to hormonal contraception. Int J Fertil Womens Med 2002;47:69–76. PubMed
  7. Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol 2007;109:339–46. CrossRef PubMed
  8. Devineni D, Skee D, Vaccaro N, et al. Pharmacokinetics and pharmacodynamics of a transdermal contraceptive patch and an oral contraceptive. J Clin Pharmacol 2007;47:497–509. . CrossRef PubMed
  9. Dieben TO, Roumen FJ, Apter D. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol 2002;100:585–93. PubMed
  10. Dittrich R, Parker L, Rosen JB, Shangold G, Creasy GW, Fisher AC; Ortho Evra/Evra 001 Study Group. Transdermal contraception: evaluation of three transdermal norelgestromin/ethinyl estradiol doses in a randomized, multicenter, dose-response study. Am J Obstet Gynecol 2002;186:15–20. CrossRef PubMed
  11. Duijkers I, Killick S, Bigrigg A, Dieben TO. A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal and thyroid function. Eur J Contracept Reprod Health Care 2004;9:131–40. CrossRef PubMed
  12. Duijkers IJ, Klipping C, Verhoeven CH, Dieben TO. Ovarian function with the contraceptive vaginal ring or an oral contraceptive: a randomized study. Hum Reprod 2004;19:2668–73. CrossRef PubMed
  13. Elkind-Hirsch KE, Darensbourg C, Ogden B, Ogden LF, Hindelang P. Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive. Contraception 2007;76:348–56. CrossRef PubMed
  14. Hedon B, Helmerhorst FM, Cronje HS, Shangold GA, Fisher AC, Creasy GW. Comparison of efficacy, cycle control, compliance, and safety in users of a contraceptive patch versus an oral contraceptive. Int J Gynaecol Obstet 2000;70(Suppl 2):B78. CrossRef
  15. Jick S, Kaye JA, Li L, Jick H. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception 2007;76:4–7. CrossRef PubMed
  16. Jick SS, Jick H. Cerebral venous sinus thrombosis in users of four hormonal contraceptives: levonorgestrel-containing oral contraceptives, norgestimate-containing oral contraceptives, desogestrel-containing oral contraceptives and the contraceptive patch. Contraception 2006;74:290–2. CrossRef PubMed
  17. Jick SS, Jick H. The contraceptive patch in relation to ischemic stroke and acute myocardial infarction. Pharmacotherapy 2007;27:218–20. CrossRef PubMed
  18. Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception 2006;73:223–8. CrossRef PubMed
  19. Magnusdóttir EM, Bjarnadóttir RI, Onundarson PT, et al. The contraceptive vaginal ring (NuvaRing) and hemostasis: a comparative study. Contraception 2004;69:461–7. CrossRef PubMed
  20. Massai R, Mäkäräinen L, Kuukankorpi A, Klipping C, Duijkers I, Dieben T. The combined contraceptive vaginal ring and bone mineral density in healthy pre-menopausal women. Hum Reprod 2005;20:2764–8. CrossRef PubMed
  21. Milsom I, Lete I, Bjertnaes A, et al. Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 µg ethinyl estradiol and 3 mg drospirenone. Hum Reprod 2006;21:2304–11. CrossRef PubMed
  22. Oddsson K, Leifels-Fischer B, de Melo NR, et al. Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Contraception 2005;71:176–82. CrossRef PubMed
  23. Pierson RA, Archer DF, Moreau M, Shangold GA, Fisher AC, Creasy GW. Ortho Evra/Evra versus oral contraceptives: follicular development and ovulation in normal cycles and after an intentional dosing error. Fertil Steril 2003;80:34–42. CrossRef PubMed
  24. Radowicki S, Skórzewska K, Szlendak K. Safety evaluation of a transdermal contraceptive system with an oral contraceptive [Polish]. Ginekol Pol 2005;76:884–9. PubMed
  25. Sabatini R, Cagiano R. Comparison profiles of cycle control, side effects and sexual satisfaction of three hormonal contraceptives. Contraception 2006;74:220–3. CrossRef PubMed
  26. Smallwood GH, Meador ML, Lenihan JP, Shangold GA, Fisher AC, Creasy GW; ORTHO EVRA/EVRA 002 Study Group. Efficacy and safety of a transdermal contraceptive system. Obstet Gynecol 2001;98:799–805. PubMed
  27. Timmer CJ, Mulders TM. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet 2000;39:233–42. CrossRef PubMed
  28. Tuppurainen M, Klimscheffskij R, Venhola M, Dieben TO. The combined contraceptive vaginal ring (NuvaRing) and lipid metabolism: a comparative study. Contraception 2004;69:389–94. CrossRef PubMed
  29. Urdl W, Apter D, Alperstein A, et al. ORTHO EVRA/EVRA 003 Study Group. Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception. Eur J Obstet Gynecol Reprod Biol 2005;121:202–10. CrossRef PubMed
  30. van den Heuvel MW, van Bragt AJM, Alnabawy AKM, Kaptein MCJ. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception 2005;72:168–74. CrossRef PubMed
  31. Veres S, Miller L, Burington B. A comparison between the vaginal ring and oral contraceptives. Obstet Gynecol 2004;104:555–63. CrossRef PubMed
  32. White T, Ozel B, Jain JK, Stanczyk FZ. Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic proteins. Contraception 2006;74:293–6. CrossRef PubMed
  33. Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril 2002;77(Suppl 2):S13–8. CrossRef PubMed
  34. Memon S, Iversen L, Hannaford PC. Is the oral contraceptive pill associated with fracture in later life? New evidence from the Royal College of General Practitioners Oral Contraception Study. Contraception 2011;84:40–7. CrossRef PubMed
  35. Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk in very young women using combined oral contraceptives. Contraception 2008;78:358–64. CrossRef PubMed
  36. Vestergaard P, Rejnmark L, Mosekilde L. Oral contraceptive use and risk of fractures. Contraception 2006;73:571–6. CrossRef PubMed
  37. Barad D, Kooperberg C, Wactawski-Wende J, Liu J, Hendrix SL, Watts NB. Prior oral contraception and postmenopausal fracture: a Women’s Health Initiative observational cohort study. Fertil Steril 2005;84:374–83. CrossRef PubMed
  38. Michaëlsson K, Baron JA, Farahmand BY, Ljunghall S. Influence of parity and lactation on hip fracture risk. Am J Epidemiol 2001;153:1166–72. CrossRef PubMed
  39. Michaëlsson K, Baron JA, Farahmand BY, Persson I, Ljunghall S. Oral-contraceptive use and risk of hip fracture: a case-control study. Lancet 1999;353:1481–4. CrossRef PubMed
  40. La Vecchia C, Tavani A, Gallus S. Oral contraceptives and risk of hip fractures. Lancet 1999;354:335–6. CrossRef PubMed
  41. Vessey M, Mant J, Painter R. Oral contraception and other factors in relation to hospital referral for fracture. Findings in a large cohort study. Contraception 1998;57:231–5. CrossRef PubMed
  42. O’Neill TW, Marsden D, Adams JE, Silman AJ. Risk factors, falls, and fracture of the distal forearm in Manchester, UK. J Epidemiol Community Health 1996;50:288–92. CrossRef PubMed
  43. Mallmin H, Ljunghall S, Persson I, Bergström R. Risk factors for fractures of the distal forearm: a population-based case-control study. Osteoporos Int 1994;4:298–304. CrossRef PubMed
  44. Cooper C, Hannaford P, Croft P, Kay CR. Oral contraceptive pill use and fractures in women: a prospective study. Bone 1993;14:41–5. CrossRef PubMed
  45. Meier C, Brauchli YB, Jick SS, Kraenzlin ME, Meier CR. Use of depot medroxyprogesterone acetate and fracture risk. J Clin Endocrinol Metab 2010;95:4909–16. CrossRef PubMed
  46. Cibula D, Skrenkova J, Hill M, Stepan JJ. Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence. Eur J Endocrinol 2012;166:1003–11. CrossRef PubMed
  47. Gai L, Jia Y, Zhang M, et al. Effect of two kinds of different combined oral contraceptives use on bone mineral density in adolescent women. Contraception 2012;86:332–6. CrossRef PubMed
  48. Scholes D, Hubbard RA, Ichikawa LE, et al. Oral contraceptive use and bone density change in adolescent and young adult women: a prospective study of age, hormone dose, and discontinuation. J Clin Endocrinol Metab 2011;96:E1380–7. CrossRef PubMed
  49. Lattakova M, Borovsky M, Payer J, Killinger Z. Oral contraception usage in relation to bone mineral density and bone turnover in adolescent girls. Eur J Contracept Reprod Health Care 2009;14:207–14. CrossRef PubMed
  50. Beksinska ME, Kleinschmidt I, Smit JA, Farley TM. Bone mineral density in a cohort of adolescents during use of norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives and after discontinuation of norethisterone enanthate. Contraception 2009;79:345–9. CrossRef PubMed
  51. Pikkarainen E, Lehtonen-Veromaa M, Möttönen T, Kautiainen H, Viikari J. Estrogen-progestin contraceptive use during adolescence prevents bone mass acquisition: a 4-year follow-up study. Contraception 2008;78:226–31. CrossRef PubMed
  52. Cromer BA, Bonny AE, Stager M, et al. Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. Fertil Steril 2008;90:2060–7. CrossRef PubMed
  53. Berenson AB, Rahman M, Breitkopf CR, Bi LX. Effects of depot medroxyprogesterone acetate and 20-µg oral contraceptives on bone mineral density. Obstet Gynecol 2008;112:788–99. CrossRef PubMed
  54. Harel Z, Riggs S, Vaz R, Flanagan P, Harel D, Machan JT. Bone accretion in adolescents using the combined estrogen and progestin transdermal contraceptive method Ortho Evra: a pilot study. J Pediatr Adolesc Gynecol 2010;23:23–31. CrossRef PubMed
  55. Cobb KL, Bachrach LK, Sowers M, et al. The effect of oral contraceptives on bone mass and stress fractures in female runners. Med Sci Sports Exerc 2007;39:1464–73. CrossRef PubMed
  56. Beksinska ME, Kleinschmidt I, Smit JA, Farley TM. Bone mineral density in adolescents using norethisterone enanthate, depot-medroxyprogesterone acetate or combined oral contraceptives for contraception. Contraception 2007;75:438–43. CrossRef PubMed
  57. Lara-Torre E, Edwards CP, Perlman S, Hertweck SP. Bone mineral density in adolescent females using depot medroxyprogesterone acetate. J Pediatr Adolesc Gynecol 2004;17:17–21. CrossRef PubMed
  58. Cromer BA, Blair JM, Mahan JD, Zibners L, Naumovski Z. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant), or oral contraceptives. J Pediatr 1996;129:671–6. CrossRef PubMed
  59. Polatti F, Perotti F, Filippa N, Gallina D, Nappi RE. Bone mass and long-term monophasic oral contraceptive treatment in young women. Contraception 1995;51:221–4. CrossRef PubMed
  60. Sørdal T, Grob P, Verhoeven C. Effects on bone mineral density of a monophasic combined oral contraceptive containing nomegestrol acetate/17ß-estradiol in comparison to levonorgestrel/ethinylestradiol. Acta Obstet Gynecol Scand 2012;91:1279–85. CrossRef PubMed
  61. Gargano V, Massaro M, Morra I, Formisano C, Di Carlo C, Nappi C. Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception 2008;78:10–5. CrossRef PubMed
  62. Nappi C, Di Spiezio Sardo A, Greco E, Tommaselli GA, Giordano E, Guida M. Effects of an oral contraceptive containing drospirenone on bone turnover and bone mineral density. Obstet Gynecol 2005;105:53–60. CrossRef PubMed
  63. Berenson AB, Radecki CM, Grady JJ, Rickert VI, Thomas A. A prospective, controlled study of the effects of hormonal contraception on bone mineral density. Obstet Gynecol 2001;98:576–82. PubMed
  64. Berenson AB, Breitkopf CR, Grady JJ, Rickert VI, Thomas A. Effects of hormonal contraception on bone mineral density after 24 months of use. Obstet Gynecol 2004;103:899–906. CrossRef PubMed
  65. Elgán C, Samsioe G, Dykes AK. Influence of smoking and oral contraceptives on bone mineral density and bone remodeling in young women: a 2-year study. Contraception 2003;67:439–47. CrossRef PubMed
  66. Elgán C, Dykes AK, Samsioe G. Bone mineral density changes in young women: a two year study. Gynecol Endocrinol 2004;19:169–77. CrossRef PubMed
  67. Endrikat J, Mih E, Düsterberg B, et al. A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 µg or 30 µg ethinylestradiol in combination with levonorgestrel on bone mineral density. Contraception 2004;69:179–87. CrossRef PubMed
  68. Paoletti AM, Orrù M, Lello S, et al. Short-term variations in bone remodeling markers of an oral contraception formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol: observational study in young postadolescent women. Contraception 2004;70:293–8. CrossRef PubMed
  69. Nappi C, Di Spiezio Sardo A, Acunzo G, et al. Effects of a low-dose and ultra-low-dose combined oral contraceptive use on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study. Contraception 2003;67:355–9. CrossRef PubMed
  70. Reed SD, Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Longitudinal changes in bone density in relation to oral contraceptive use. Contraception 2003;68:177–82. CrossRef PubMed
  71. Cobb KL, Kelsey JL, Sidney S, Ettinger B, Lewis CE. Oral contraceptives and bone mineral density in white and black women in CARDIA. Coronary Risk Development in Young Adults. Osteoporos Int 2002;13:893–900. CrossRef PubMed
  72. Burr DB, Yoshikawa T, Teegarden D, et al. Exercise and oral contraceptive use suppress the normal age-related increase in bone mass and strength of the femoral neck in women 18–31 years of age. Bone 2000;27:855–63. CrossRef PubMed
  73. Recker RR, Davies KM, Hinders SM, Heaney RP, Stegman MR, Kimmel DB. Bone gain in young adult women. JAMA 1992;268:2403–8. CrossRef PubMed
  74. Mazess RB, Barden HS. Bone density in premenopausal women: effects of age, dietary intake, physical activity, smoking, and birth-control pills. Am J Clin Nutr 1991;53:132–42. PubMed
  75. Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas 2006;54:176–80. CrossRef PubMed
  76. Gambacciani M, Spinetti A, Taponeco F, Cappagli B, Piaggesi L, Fioretti P. Longitudinal evaluation of perimenopausal vertebral bone loss: effects of a low-dose oral contraceptive preparation on bone mineral density and metabolism. Obstet Gynecol 1994;83:392–6. PubMed
  77. Gambacciani M, Spinetti A, Cappagli B, et al. Hormone replacement therapy in perimenopausal women with a low dose oral contraceptive preparation: effects on bone mineral density and metabolism. Maturitas 1994;19:125–31. CrossRef PubMed
  78. Gambacciani M, Cappagli B, Ciaponi M, Benussi C, Genazzani AR. Hormone replacement therapy in perimenopause: effect of a low dose oral contraceptive preparation on bone quantitative ultrasound characteristics. Menopause 1999;6:43–8. CrossRef PubMed
  79. Volpe A, Malmusi S, Zanni AL, Landi S, Cagnacci A. Oral contraceptives and bone metabolism. Eur J Contracept Reprod Health Care 1997;2:225–8. CrossRef PubMed
  80. Hansen MA, Overgaard K, Riis BJ, Christiansen C. Potential risk factors for development of postmenopausal osteoporosis—examined over a 12-year period. Osteoporos Int 1991;1:95–102. CrossRef PubMed
  81. Shargil AA. Hormone replacement therapy in perimenopausal women with a triphasic contraceptive compound: a three-year prospective study. Int J Fertil 1985;30:15, 18–28. PubMed
  82. Taechakraichana N, Limpaphayom K, Ninlagarn T, Panyakhamlerd K, Chaikittisilpa S, Dusitsin N. A randomized trial of oral contraceptive and hormone replacement therapy on bone mineral density and coronary heart disease risk factors in postmenopausal women. Obstet Gynecol 2000;95:87–94. PubMed
  83. Taechakraichana N, Jaisamrarn U, Panyakhamlerd K, Chaikittisilpa S, Limpaphayom K. Difference in bone acquisition among hormonally treated postmenopausal women with normal and low bone mass. J Med Assoc Thai 2001;84(Suppl 2):S586–92. PubMed
  84. Grimes DA, Schulz KF. Surrogate end points in clinical research: hazardous to your health. Obstet Gynecol 2005;105:1114–8. CrossRef PubMed
  85. Schönau E. The peak bone mass concept: is it still relevant? Pediatr Nephrol 2004;19:825–31. CrossRef PubMed
  86. Cohen A, Shane E. Treatment of premenopausal women with low bone mineral density. Curr Osteoporos Rep 2008;6:39–46. CrossRef PubMed
  87. US Department of Health and Human Services. Healthy people 2020: maternal, infant, and child health objectives. Washington, DC: US Department of Health and Human Services; 2015. http://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health/objectives.
  88. Tepper NK, Phillips SJ, Kapp N, Gaffield ME, Curtis KM. Combined hormonal contraceptive use among breastfeeding women: an updated systematic review. Contraception 2015;S0010-7824(15)00218-8. PubMed
  89. Petersen JF, Bergholt T, Nielsen AK, Paidas MJ, Løkkegaard EC. Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995–2009. Thromb Haemost 2014;112:73–8. CrossRef PubMed
  90. Jackson E, Curtis KM, Gaffield ME. Risk of venous thromboembolism during the postpartum period: a systematic review. Obstet Gynecol 2011;117:691–703. CrossRef PubMed
  91. Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014;370:1307–15. CrossRef PubMed
  92. Sultan AA, Tata LJ, West J, et al. Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom. Blood 2013;121:3953–61. CrossRef PubMed
  93. Sultan AA, West J, Tata LJ, Fleming KM, Nelson-Piercy C, Grainge MJ. Risk of first venous thromboembolism in and around pregnancy: a population-based cohort study. Br J Haematol 2012;156:366–73. CrossRef PubMed
  94. Tepper NK, Boulet SL, Whiteman MK, et al. Postpartum venous thromboembolism: incidence and risk factors. Obstet Gynecol 2014;123:987–96. CrossRef PubMed
  95. Jackson E, Glasier A. Return of ovulation and menses in postpartum nonlactating women: a systematic review. Obstet Gynecol 2011;117:657–62. CrossRef PubMed
  96. Lähteenmäki P. Influence of oral contraceptives on immediate postabortal pituitary-ovarian function. Acta Obstet Gynecol Scand Suppl 1978;76:1–43. PubMed
  97. Lähteenmäki P, Rasi V, Luukkainen T, Myllyä G. Coagulation factors in women using oral contraceptives or intrauterine contraceptive devices immediately after abortion. Am J Obstet Gynecol 1981;141:175–9. PubMed
  98. Martin CW, Brown AH, Baird DT. A pilot study of the effect of methotrexate or combined oral contraceptive on bleeding patterns after induction of abortion with mifepristone and a prostaglandin pessary. Contraception 1998;58:99–103. CrossRef PubMed
  99. Niswonger JW, London GD, Anderson GV, Wolfe L. Oral contraceptives during immediate postabortal period. Obstet Gynecol 1968;32:325–7. PubMed
  100. Peterson WF. Contraceptive therapy following therapeutic abortion: an analysis. Obstet Gynecol 1974;44:853–7. PubMed
  101. Tang OS, Gao PP, Cheng L, Lee SW, Ho PC. A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Hum Reprod 1999;14:722–5. CrossRef PubMed
  102. Tang OS, Xu J, Cheng L, Lee SW, Ho PC. The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial. Hum Reprod 2002;17:99–102. CrossRef PubMed
  103. Fine PM, Tryggestad J, Meyers NJ, Sangi-Haghpeykar H. Safety and acceptability with the use of a contraceptive vaginal ring after surgical or medical abortion. Contraception 2007;75:367–71. CrossRef PubMed
  104. Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000;284:72–8. CrossRef PubMed
  105. Jick SS, Walker AM, Stergachis A, Jick H. Oral contraceptives and breast cancer. Br J Cancer 1989;59:618–21. CrossRef PubMed
  106. Khader YS, Rice J, John L, Abueita O. Oral contraceptives use and the risk of myocardial infarction: a meta-analysis. Contraception 2003;68:11–7. CrossRef PubMed
  107. Lawson DH, Davidson JF, Jick H. Oral contraceptive use and venous thromboembolism: absence of an effect of smoking. BMJ 1977;2:729–30. CrossRef PubMed
  108. Lidegaard O, Edström B, Kreiner S. Oral contraceptives and venous thromboembolism. A case-control study. Contraception 1998;57:291–301. CrossRef PubMed
  109. Nightingale AL, Lawrenson RA, Simpson EL, Williams TJ, MacRae KD, Farmer RD. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contracept Reprod Health Care 2000;5:265–74. CrossRef PubMed
  110. Petitti DB, Wingerd J, Pellegrin F, Ramcharan S. Risk of vascular disease in women. Smoking, oral contraceptives, noncontraceptive estrogens, and other factors. JAMA 1979;242:1150–4. CrossRef PubMed
  111. Rosenberg L, Palmer JR, Rao RS, Shapiro S. Low-dose oral contraceptive use and the risk of myocardial infarction. Arch Intern Med 2001;161:1065–70. CrossRef PubMed
  112. Straneva P, Hinderliter A, Wells E, Lenahan H, Girdler S. Smoking, oral contraceptives, and cardiovascular reactivity to stress. Obstet Gynecol 2000;95:78–83. PubMed
  113. Tanis BC, van den Bosch MA, Kemmeren JM, et al. Oral contraceptives and the risk of myocardial infarction. N Engl J Med 2001;345:1787–93. CrossRef PubMed
  114. Van den Bosch MA, Kemmeren JM, Tanis BC, et al. The RATIO study: oral contraceptives and the risk of peripheral arterial disease in young women. J Thromb Hemost 2003;1:439–44.
  115. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. Lancet 1995;346:1575–82. CrossRef PubMed
  116. Collaborative Group for the Study of Stroke in Young Women. Oral contraceptives and stroke in young women. Associated risk factors. JAMA 1975;231:718–22. CrossRef PubMed
  117. Horton L, Simmons K, Curtis KM. Combined hormonal contraceptive use among obese women and risk for cardiovascular events: a systematic review. Contraception 2016. Epub June 1, 2016. CrossRef
  118. Brunner Huber LR, Hogue CJ, Stein AD, Drews C, Zieman M. Body mass index and risk for oral contraceptive failure: a case-cohort study in South Carolina. Ann Epidemiol 2006;16:637–43. CrossRef PubMed
  119. Brunner Huber LR, Toth JL. Obesity and oral contraceptive failure: findings from the 2002 National Survey of Family Growth. Am J Epidemiol 2007;166:1306–11. CrossRef PubMed
  120. Brunner LR, Hogue CJ. The role of body weight in oral contraceptive failure: results from the 1995 national survey of family growth. Ann Epidemiol 2005;15:492–9. CrossRef PubMed
  121. Holt VL, Cushing-Haugen KL, Daling JR. Body weight and risk of oral contraceptive failure. Obstet Gynecol 2002;99:820–7. PubMed
  122. Holt VL, Scholes D, Wicklund KG, Cushing-Haugen KL, Daling JR. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol 2005;105:46–52. CrossRef PubMed
  123. Trussell J, Schwarz EB, Guthrie K. Obesity and oral contraceptive pill failure. Contraception 2009;79:334–8. CrossRef PubMed
  124. Vessey M. Oral contraceptive failures and body weight: findings in a large cohort study. J Fam Plann Reprod Health Care 2001;27:90–1. CrossRef PubMed
  125. Yamazaki M, Dwyer K, Sobhan M, et al. Effect of obesity on the effectiveness of hormonal contraceptives: an individual participant data meta-analysis. Contraception 2015;92:445–52. CrossRef PubMed
  126. Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril 2002;77(Suppl 2):S13–8. CrossRef PubMed
  127. O’Connell KJ, Osborne LM, Westhoff C. Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive. Contraception 2005;72:323–7. CrossRef PubMed
  128. Paulen ME, Zapata LB, Cansino C, Curtis KM, Jamieson DJ. Contraceptive use among women with a history of bariatric surgery: a systematic review. Contraception 2010;82:86–94. CrossRef PubMed
  129. Lidegaard Ø, Edström B, Kreiner S. Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception 2002;65:187–96. CrossRef PubMed
  130. Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners’ oral contraception study. BMJ 1989;298:165–8. CrossRef PubMed
  131. D’Avanzo B, La Vecchia C, Negri E, Parazzini F, Franceschi S. Oral contraceptive use and risk of myocardial infarction: an Italian case-control study. J Epidemiol Community Health 1994;48:324–5. CrossRef PubMed
  132. Dunn NR, Faragher B, Thorogood M, et al. Risk of myocardial infarction in young female smokers. Heart 1999;82:581–3. CrossRef PubMed
  133. Hannaford PC, Croft PR, Kay CR. Oral contraception and stroke. Evidence from the Royal College of General Practitioners’ Oral Contraception Study. Stroke 1994;25:935–42. CrossRef PubMed
  134. Heinemann LA, Lewis MA, Spitzer WO, Thorogood M, Guggenmoos-Holzmann I, Bruppacher R; Transnational Research Group on Oral Contraceptives and the Health of Young Women. Thromboembolic stroke in young women. A European case-control study on oral contraceptives. Contraception 1998;57:29–37. CrossRef PubMed
  135. Kemmeren JM, Tanis BC, van den Bosch MA, et al. Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study: oral contraceptives and the risk of ischemic stroke. Stroke 2002;33:1202–8. CrossRef PubMed
  136. Lewis MA, Heinemann LA, Spitzer WO, MacRae KD, Bruppacher R. The use of oral contraceptives and the occurrence of acute myocardial infarction in young women. Results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Contraception 1997;56:129–40. CrossRef PubMed
  137. Lidegaard O. Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study. BMJ 1993;306:956–63. CrossRef PubMed
  138. Lidegaard O. Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease. Br J Obstet Gynaecol 1995;102:153–9. CrossRef PubMed
  139. Lubianca JN, Faccin CS, Fuchs FD. Oral contraceptives: a risk factor for uncontrolled blood pressure among hypertensive women. Contraception 2003;67:19–24. CrossRef PubMed
  140. Narkiewicz K, Graniero GR, D’Este D, Mattarei M, Zonzin P, Palatini P. Ambulatory blood pressure in mild hypertensive women taking oral contraceptives. A case-control study. Am J Hypertens 1995;8:249–53. CrossRef PubMed
  141. Siritho S, Thrift AG, McNeil JJ, You RX, Davis SM, Donnan GA; Melbourne Risk Factor Study (MERFS) Group. Risk of ischemic stroke among users of the oral contraceptive pill: The Melbourne Risk Factor Study (MERFS) Group. Stroke 2003;34:1575–80. CrossRef PubMed
  142. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet 1996;348:498–505. CrossRef PubMed
  143. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet 1997;349:1202–9. CrossRef PubMed
  144. Lubianca JN, Moreira LB, Gus M, Fuchs FD. Stopping oral contraceptives: an effective blood pressure-lowering intervention in women with hypertension. J Hum Hypertens 2005;19:451–5. CrossRef PubMed
  145. Aberg H, Karlsson L, Melander S. Studies on toxaemia of pregnancy with special reference to blood pressure. II. Results after 6–11 years’ follow-up. Ups J Med Sci 1978;83:97–102. CrossRef PubMed
  146. Carmichael SM, Taylor MM, Ayers CR. Oral contraceptives, hypertension, and toxemia. Obstet Gynecol 1970;35:371–6. PubMed
  147. Meinel H, Ihle R, Laschinski M. [Effect of hormonal contraceptives on blood pressure following pregnancy-induced hypertension]. Zentralbl Gynakol 1987;109:527–31. PubMed
  148. Pritchard JA, Pritchard SA. Blood pressure response to estrogen-progestin oral contraceptive after pregnancy-induced hypertension. Am J Obstet Gynecol 1977;129:733–9 . CrossRef PubMed
  149. Sibai BM, Taslimi MM, el-Nazer A, Amon E, Mabie BC, Ryan GM. Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. Am J Obstet Gynecol 1986;155:501–7. CrossRef PubMed
  150. Sibai BM, Ramadan MK, Chari RS, Friedman SA. Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis. Am J Obstet Gynecol 1995;172:125–9. CrossRef PubMed
  151. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet 1996;348:505–10. CrossRef PubMed
  152. Sidney S, Petitti DB, Soff GA, Cundiff DL, Tolan KK, Quesenberry CP . Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception 2004;70:3–10. CrossRef PubMed
  153. Andersen BS, Olsen J, Nielsen GL, et al. Third generation oral contraceptives and heritable thrombophilia as risk factors of non-fatal venous thromboembolism. Thromb Haemost 1998;79:28–31. PubMed
  154. Aznar J, Mira Y, Vayá A, et al. Factor V Leiden and prothrombin G20210A mutations in young adults with cryptogenic ischemic stroke. Thromb Haemost 2004;91:1031–4. PubMed
  155. Bennet L, Odeberg H. Resistance to activated protein C, highly prevalent amongst users of oral contraceptives with venous thromboembolism. J Intern Med 1998;243:27–32. CrossRef PubMed
  156. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects.[comment]. Arch Intern Med 2000;160:49–52. CrossRef PubMed
  157. Bloemenkamp KW, Helmerhorst FM, Rosendaal FR, Vandenbroucke JP, Büller HR. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995;346:1593–6. CrossRef PubMed
  158. de Bruijn SF, Stam J, Koopman MM, Vandenbroucke JP; The Cerebral Venous Sinus Thrombosis Study Group. Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in [correction of who are] carriers of hereditary prothrombotic conditions. BMJ 1998;316:589–92. CrossRef PubMed
  159. Emmerich J, Rosendaal FR, Cattaneo M, et al. Study Group for Pooled-Analysis in Venous Thromboembolism. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism—pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Thromb Haemost 2001;86:809–16. PubMed
  160. Gadelha T, André C, Jucá AA, Nucci M. Prothrombin 20210A and oral contraceptive use as risk factors for cerebral venous thrombosis. Cerebrovasc Dis 2005;19:49–52. CrossRef PubMed
  161. Legnani C, Palareti G, Guazzaloca G, et al. Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use. Eur Heart J 2002;23:984–90. CrossRef PubMed
  162. Martinelli I, Battaglioli T, Bucciarelli P, Passamonti SM, Mannucci PM. Risk factors and recurrence rate of primary deep vein thrombosis of the upper extremities. Circulation 2004;110:566–70. CrossRef PubMed
  163. Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.[comment]. N Engl J Med 1998;338:1793–7. CrossRef PubMed
  164. Martinelli I, Taioli E, Bucciarelli P, Akhavan S, Mannucci PM. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol 1999;19:700–3. CrossRef PubMed
  165. Middeldorp S, Meinardi JR, Koopman MM, et al. A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism.[comment]. Ann Intern Med 2001;135:322–7. CrossRef PubMed
  166. Pabinger I, Schneider B; The GTH Study Group on Natural Inhibitors. Thrombotic risk of women with hereditary antithrombin III-, protein C- and protein S-deficiency taking oral contraceptive medication. Thromb Haemost 1994;71:548–52. PubMed
  167. Pezzini A, Grassi M, Iacoviello L, et al. Inherited thrombophilia and stratification of ischaemic stroke risk among users of oral contraceptives. J Neurol Neurosurg Psychiatry 2007;78:271–6. CrossRef PubMed
  168. Santamaría A, Mateo J, Oliver A, et al. Risk of thrombosis associated with oral contraceptives of women from 97 families with inherited thrombophilia: high risk of thrombosis in carriers of the G20210A mutation of the prothrombin gene. Haematologica 2001;86:965–71. PubMed
  169. Slooter AJ, Rosendaal FR, Tanis BC, Kemmeren JM, van der Graaf Y, Algra A. Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. J Thromb Haemost 2005;3:1213–7. CrossRef PubMed
  170. Spannagl M, Heinemann LA, Schramm W. Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism? Eur J Contracept Reprod Health Care 2000;5:105–12. CrossRef PubMed
  171. van Boven HH, Vandenbroucke JP, Briët E, Rosendaal FR. Gene-gene and gene-environment interactions determine risk of thrombosis in families with inherited antithrombin deficiency. Blood 1999;94:2590–4. PubMed
  172. van Vlijmen EF, Brouwer JL, Veeger NJ, Eskes TK, de Graeff PA, van der Meer J. Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study. Arch Intern Med 2007;167:282–9. CrossRef PubMed
  173. Vandenbroucke JP, Koster T, Rosendaal FR, Briët E, Reitsma PH, Bertina RM. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation.[comment]. Lancet 1994;344:1453–7. CrossRef PubMed
  174. Vayá A, Mira Y, Mateo J, et al. Prothrombin G20210A mutation and oral contraceptive use increase upper-extremity deep vein thrombotic risk. Thromb Haemost 2003;89:452–7. PubMed
  175. Martinelli I, Battaglioli T, Burgo I, Di Domenico S, Mannucci PM. Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke. Haematologica 2006;91:844–7. PubMed
  176. Tepper NK, Marchbanks PA, Curtis KM. Superficial venous disease and combined hormonal contraceptives: a systematic review. Contraception 2015;S0010-7824(15)00128-6. PubMed
  177. Tepper NK, Paulen ME, Marchbanks PA, Curtis KM. Safety of contraceptive use among women with peripartum cardiomyopathy: a systematic review. Contraception 2010;82:95–101. CrossRef PubMed
  178. The Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Little, Brown and Co; 1994.
  179. Bernatsky S, Clarke A, Ramsey-Goldman R, et al. Hormonal exposures and breast cancer in a sample of women with systemic lupus erythematosus. Rheumatology (Oxford) 2004;43:1178–81. CrossRef PubMed
  180. Bernatsky S, Ramsey-Goldman R, Gordon C, et al. Factors associated with abnormal Pap results in systemic lupus erythematosus. Rheumatology (Oxford) 2004;43:1386–9. CrossRef PubMed
  181. Chopra N, Koren S, Greer WL, et al. Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol 2002;29:1683–8. PubMed
  182. Esdaile JM, Abrahamowicz M, Grodzicky T, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 2001;44:2331–7. CrossRef PubMed
  183. Julkunen HA. Oral contraceptives in systemic lupus erythematosus: side-effects and influence on the activity of SLE. Scand J Rheumatol 1991;20:427–33. CrossRef PubMed
  184. Julkunen HA, Kaaja R, Friman C. Contraceptive practice in women with systemic lupus erythematosus. Br J Rheumatol 1993;32:227–30. CrossRef PubMed
  185. Jungers P, Dougados M, Pélissier C, et al. Influence of oral contraceptive therapy on the activity of systemic lupus erythematosus. Arthritis Rheum 1982;25:618–23. CrossRef PubMed
  186. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 1997;145:408–15. CrossRef PubMed
  187. McAlindon T, Giannotta L, Taub N, D’Cruz D, Hughes G. Environmental factors predicting nephritis in systemic lupus erythematosus. Ann Rheum Dis 1993;52:720–4. CrossRef PubMed
  188. McDonald J, Stewart J, Urowitz MB, Gladman DD. Peripheral vascular disease in patients with systemic lupus erythematosus. Ann Rheum Dis 1992;51:56–60. CrossRef PubMed
  189. Mintz G, Gutiérrez G, Delezé M, Rodríguez E. Contraception with progestagens in systemic lupus erythematosus. Contraception 1984;30:29–38. CrossRef PubMed
  190. Petri M. Musculoskeletal complications of systemic lupus erythematosus in the Hopkins Lupus Cohort: an update. Arthritis Care Res 1995;8:137–45. CrossRef PubMed
  191. Petri M. Lupus in Baltimore: evidence-based ‘clinical pearls’ from the Hopkins Lupus Cohort. Lupus 2005;14:970–3. CrossRef PubMed
  192. Petri M, Kim MY, Kalunian KC, et al. ; OC-SELENA Trial. Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005;353:2550–8. CrossRef PubMed
  193. Sánchez-Guerrero J, Uribe AG, Jiménez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005;353:2539–49. CrossRef PubMed
  194. Sarabi ZS, Chang E, Bobba R, et al. Incidence rates of arterial and venous thrombosis after diagnosis of systemic lupus erythematosus. Arthritis Rheum 2005;53:609–12. CrossRef PubMed
  195. Schaedel ZE, Dolan G, Powell MC. The use of the levonorgestrel-releasing intrauterine system in the management of menorrhagia in women with hemostatic disorders. Am J Obstet Gynecol 2005;193:1361–3. CrossRef PubMed
  196. Somers E, Magder LS, Petri M. Antiphospholipid antibodies and incidence of venous thrombosis in a cohort of patients with systemic lupus erythematosus. J Rheumatol 2002;29:2531–6. PubMed
  197. Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 1976;60:221–5. CrossRef PubMed
  198. Choojitarom K, Verasertniyom O, Totemchokchyakarn K, Nantiruj K, Sumethkul V, Janwityanujit S. Lupus nephritis and Raynaud’s phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies. Clin Rheumatol 2008;27:345–51. CrossRef PubMed
  199. Wahl DG, Guillemin F, de Maistre E, Perret C, Lecompte T, Thibaut G. Risk for venous thrombosis related to antiphospholipid antibodies in systemic lupus erythematosus—a meta-analysis. Lupus 1997;6:467–73. CrossRef PubMed
  200. Farr SL, Folger SG, Paulen ME, Curtis KM. Safety of contraceptive methods for women with rheumatoid arthritis: a systematic review. Contraception 2010;82:64–71. CrossRef PubMed
  201. Tepper N, Whiteman M, Zapata L, Marchbanks P, Curtis K. Safety of hormonal contraceptives among women with migraine: a systematic review. Contraception 2016. Epub May 3, 2016. CrossRef
  202. Xu Z, Li Y, Tang S, Huang X, Chen T. Current use of oral contraceptives and the risk of first-ever ischemic stroke: A meta-analysis of observational studies. Thromb Res 2015;136:52–60. CrossRef PubMed
  203. Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ 2005;330:63. CrossRef PubMed
  204. Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009;339:b3914. CrossRef PubMed
  205. Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 2010;123:612–24. CrossRef PubMed
  206. Zapata LB, Oduyebo T, Whiteman MK, Marchbanks PA, Curtis KM. Contraceptive use among women with multiple sclerosis: a systematic review. Contraception . In press 2016.
  207. Pagano HP, Zapata LB, Berry-Bibee E, Nanda K, Curtis KM. Safety of hormonal contraception and intrauterine devices among women with depressive and bipolar disorders: a systematic review. Contraception 2016. Epub June 27, 2016. CrossRef
  208. Iyer V, Farquhar C, Jepson R. Oral contraceptive pills for heavy menstrual bleeding. Cochrane Database Syst Rev 2000;(2):CD000154. PubMed
  209. Davis L, Kennedy SS, Moore J, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev 2007;(3):CD001019. PubMed
  210. Hendrix SL, Alexander NJ. Primary dysmenorrhea treatment with a desogestrel-containing low-dose oral contraceptive. Contraception 2002;66:393–9. CrossRef PubMed
  211. Proctor ML, Roberts H, Farquhar CM. Combined oral contraceptive pill (OCP) as treatment for primary dysmenorrhoea. Cochrane Database Syst Rev 2001;(4):CD002120. PubMed
  212. Gaffield ME, Kapp N, Curtis KM. Combined oral contraceptive and intrauterine device use among women with gestational trophoblastic disease. Contraception 2009;80:363–71. CrossRef PubMed
  213. Smith JS, Green J, Berrington de Gonzalez A, et al. Cervical cancer and use of hormonal contraceptives: a systematic review. Lancet 2003;361:1159–67. CrossRef PubMed
  214. Black MM, Barclay THC, Polednak A, Kwon CS, Leis HP , Pilnik S. Family history, oral contraceptive usage, and breast cancer. Cancer 1983;51:2147–51. CrossRef PubMed
  215. Brinton LA, Hoover R, Szklo M, Fraumeni JF . Oral contraceptives and breast cancer. Int J Epidemiol 1982;11:316–22. CrossRef PubMed
  216. Brohet RM, Goldgar DE, Easton DF, et al. Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 2007;25:3831–6. CrossRef PubMed
  217. Claus EB, Stowe M, Carter D. Oral contraceptives and the risk of ductal breast carcinoma in situ. Breast Cancer Res Treat 2003;81:129–36. CrossRef PubMed
  218. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001;358:1389–99. CrossRef PubMed
  219. Grabrick DM, Hartmann LC, Cerhan JR, et al. Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer.[comment]. JAMA 2000;284:1791–8. CrossRef PubMed
  220. Gronwald J, Byrski T, Huzarski T, et al. Influence of selected lifestyle factors on breast and ovarian cancer risk in BRCA1 mutation carriers from Poland. Breast Cancer Res Treat 2006;95:105–9. CrossRef PubMed
  221. Haile RW, Thomas DC, McGuire V, et al. kConFab Investigators; Ontario Cancer Genetics Network Investigators. BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50. Cancer Epidemiol Biomarkers Prev 2006;15:1863–70. CrossRef PubMed
  222. Harris NV, Weiss NS, Francis AM, Polissar L. Breast cancer in relation to patterns of oral contraceptive use. Am J Epidemiol 1982;116:643–51. PubMed
  223. Hennekens CH, Speizer FE, Lipnick RJ, et al. A case-control study of oral contraceptive use and breast cancer. J Natl Cancer Inst 1984;72:39–42. PubMed
  224. Jernström H, Loman N, Johannsson OT, Borg A, Olsson H. Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing. Eur J Cancer 2005;41:2312–20. CrossRef PubMed
  225. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002;346:2025–32. CrossRef PubMed
  226. Milne RL, Knight JA, John EM, et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 2005;14:350–6. CrossRef PubMed
  227. Narod SA, Dubé MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2002;94:1773–9. CrossRef PubMed
  228. Rosenberg L, Palmer JR, Rao RS, et al. Case-control study of oral contraceptive use and risk of breast cancer. Am J Epidemiol 1996;143:25–37. CrossRef PubMed
  229. Silvera SA, Miller AB, Rohan TE. Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study. Cancer Causes Control 2005;16:1059–63. CrossRef PubMed
  230. Ursin G, Henderson BE, Haile RW, et al. Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/BRCA2 mutations more than in other women? Cancer Res 1997;57:3678–81. PubMed
  231. Ursin G, Ross RK, Sullivan-Halley J, Hanisch R, Henderson B, Bernstein L. Use of oral contraceptives and risk of breast cancer in young women. Breast Cancer Res Treat 1998;50:175–84. CrossRef PubMed
  232. Polis CB, Phillips SJ, Curtis KM, et al. Hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence. Contraception 2014;90:360–90. CrossRef PubMed
  233. Polis CB, Phillips SJ, Curtis KM. Hormonal contraceptive use and female-to-male HIV transmission: a systematic review of the epidemiologic evidence. AIDS 2013;27:493–505. CrossRef PubMed
  234. Phillips SJ, Polis CB, Curtis KM. The safety of hormonal contraceptives for women living with HIV and their sexual partners. Contraception 2016;93:11–6 . CrossRef PubMed
  235. Phillips SJ, Curtis KM, Polis CB. Effect of hormonal contraceptive methods on HIV disease progression: a systematic review. AIDS 2013;27:787–94. CrossRef PubMed
  236. el-Raghy I, Back DJ, Osman F, Orme ML, Fathalla M. Contraceptive steroid concentrations in women with early active schistosomiasis: lack of effect of antischistosomal drugs. Contraception 1986;33:373–7. CrossRef PubMed
  237. Gad-el-Mawla N, Abdallah A. Liver function in bilharzial females receiving contraceptive pills. Acta Hepatosplenol 1969;16:308–10. PubMed
  238. Gad-el-Mawla N, el-Roubi O, Sabet S, Abdallah A. Plasma lipids and lipoproteins in bilharzial females during oral contraceptive therapy. J Egypt Med Assoc 1972;55:137–47. PubMed
  239. Shaaban MM, Hammad WA, Falthalla MF, et al. Effects of oral contraception on liver function tests and serum proteins in women with active schistosomiasis. Contraception 1982;26:75–82. CrossRef PubMed
  240. Shaaban MM, Ghaneimah SA, Mohamed MA, Abdel-Chani S, Mostafa SA. Effect of oral contraception on serum bile acid. Int J Gynaecol Obstet 1984;22:111–5. CrossRef PubMed
  241. Sy FS, Osteria TS, Opiniano V, Gler S. Effect of oral contraceptive on liver function tests of women with schistosomiasis in the Philippines. Contraception 1986;34:283–94. CrossRef PubMed
  242. Tagy AH, Saker ME, Moussa AA, Kolgah A. The effect of low-dose combined oral contraceptive pills versus injectable contraceptive (Depot Provera) on liver function tests of women with compensated bilharzial liver fibrosis. Contraception 2001;64:173–6. CrossRef PubMed
  243. Beck P, Wells SA. Comparison of the mechanisms underlying carbohydrate intolerance in subclinical diabetic women during pregnancy and during post-partum oral contraceptive steroid treatment. J Clin Endocrinol Metab 1969;29:807–18. CrossRef PubMed
  244. Kjos SL, Peters RK, Xiang A, Thomas D, Schaefer U, Buchanan TA. Contraception and the risk of type 2 diabetes mellitus in Latina women with prior gestational diabetes mellitus. JAMA 1998;280:533–8. CrossRef PubMed
  245. Kung AW, Ma JT, Wong VC, et al. Glucose and lipid metabolism with triphasic oral contraceptives in women with history of gestational diabetes. Contraception 1987;35:257–69. CrossRef PubMed
  246. R&aringdberg T, Gustafson A, Skryten A, Karlsson K. Metabolic studies in gestational diabetic women during contraceptive treatment: effects on glucose tolerance and fatty acid composition of serum lipids. Gynecol Obstet Invest 1982;13:17–29. CrossRef PubMed
  247. Skouby SO, Andersen O, Kühl C. Oral contraceptives and insulin receptor binding in normal women and those with previous gestational diabetes. Am J Obstet Gynecol 1986;155:802–7. CrossRef PubMed
  248. Skouby SO, Andersen O, Saurbrey N, Kühl C. Oral contraception and insulin sensitivity: in vivo assessment in normal women and women with previous gestational diabetes. J Clin Endocrinol Metab 1987;64:519–23. CrossRef PubMed
  249. Skouby SO, Mølsted-Pedersen L, Kühl C. Low dosage oral contraception in women with previous gestational diabetes. Obstet Gynecol 1982;59:325–8. PubMed
  250. Xiang AH, Kawakubo M, Kjos SL, Buchanan TA. Long-acting injectable progestin contraception and risk of type 2 diabetes in Latino women with prior gestational diabetes mellitus. Diabetes Care 2006;29:613–7. CrossRef PubMed
  251. Kjos SL, Shoupe D, Douyan S, et al. Effect of low-dose oral contraceptives on carbohydrate and lipid metabolism in women with recent gestational diabetes: results of a controlled, randomized, prospective study. Am J Obstet Gynecol 1990;163:1822–7. CrossRef PubMed
  252. R&aringdberg T, Gustafson A, Skryten A, Karlsson K. Metabolic studies in women with previous gestational diabetes during contraceptive treatment: effects on serum lipids and high density lipoproteins. Acta Endocrinol (Copenh) 1982;101:134–9. PubMed
  253. Skouby SO, Kühl C, Mølsted-Pedersen L, Petersen K, Christensen MS. Triphasic oral contraception: metabolic effects in normal women and those with previous gestational diabetes. Am J Obstet Gynecol 1985;153:495–500. CrossRef PubMed
  254. Beck P, Arnett DM, Alsever RN, Eaton RP. Effect of contraceptive steroids on arginine- stimulated glucagon and insulin secretion in women. II. Carbohydrate and lipid physiology in insulin-dependent diabetics. Metabolism 1976;25:23–31 . CrossRef PubMed
  255. Diab KM, Zaki MM. Contraception in diabetic women: comparative metabolic study of Norplant, depot medroxyprogesterone acetate, low dose oral contraceptive pill and CuT380A. J Obstet Gynaecol Res 2000;26:17–26. CrossRef PubMed
  256. Garg SK, Chase HP, Marshall G, Hoops SL, Holmes DL, Jackson WE. Oral contraceptives and renal and retinal complications in young women with insulin-dependent diabetes mellitus. JAMA 1994;271:1099–102. CrossRef PubMed
  257. Grigoryan OR, Grodnitskaya EE, Andreeva EN, Shestakova MV, Melnichenko GA, Dedov II. Contraception in perimenopausal women with diabetes mellitus. Gynecol Endocrinol 2006;22:198–206. CrossRef PubMed
  258. Margolis KL, Adami H-O, Luo J, Ye W, Weiderpass E. A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women. Fertil Steril 2007;88:310–6. CrossRef PubMed
  259. Petersen KR, Skouby SO, Jespersen J. Balance of coagulation activity with fibrinolysis during use of oral contraceptives in women with insulin-dependent diabetes mellitus. Int J Fertil Menopausal Stud 1995;40(Suppl 2):105–11. PubMed
  260. Petersen KR, Skouby SO, Sidelmann J, Jespersen J. Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus. Metabolism 1994;43:1379–83. CrossRef PubMed
  261. R&aringdberg T, Gustafson A, Skryten A, Karlsson K. Oral contraception in diabetic women. A cross-over study on serum and high density lipoprotein (HDL) lipids and diabetes control during progestogen and combined estrogen/progestogen contraception. Horm Metab Res 1982;14:61–5. PubMed
  262. Skouby SO, Jensen BM, Kühl C, Mølsted-Pedersen L, Svenstrup B, Nielsen J. Hormonal contraception in diabetic women: acceptability and influence on diabetes control and ovarian function of a nonalkylated estrogen/progestogen compound. Contraception 1985;32:23–31. CrossRef PubMed
  263. Skouby SO, Mølsted-Pedersen L, Kühl C, Bennet P. Oral contraceptives in diabetic women: metabolic effects of four compounds with different estrogen/progestogen profiles. Fertil Steril 1986;46:858–64 . CrossRef PubMed
  264. Zapata LB, Paulen ME, Cansino C, Marchbanks PA, Curtis KM. Contraceptive use among women with inflammatory bowel disease: A systematic review. Contraception 2010;82:72–85. CrossRef PubMed
  265. Kapp N, Tilley IB, Curtis KM. The effects of hormonal contraceptive use among women with viral hepatitis or cirrhosis of the liver: a systematic review. Contraception 2009;80:381–6. CrossRef PubMed
  266. Kapp N, Curtis KM. Hormonal contraceptive use among women with liver tumors: a systematic review. Contraception 2009;80:387–90. CrossRef PubMed
  267. Whiteman MK, Oduyebo T, Zapata LB, Walker S, Curtis KM. Contraceptive safety among women with cystic fibrosis: a systematic review. Contraception 2016. Epub June 7, 2016. CrossRef
  268. Paulen ME, Folger SG, Curtis KM, Jamieson DJ. Contraceptive use among solid organ transplant patients: a systematic review. Contraception 2010;82:102–12. CrossRef PubMed
  269. Aweeka FT, Rosenkranz SL, Segal Y, et al. NIAID AIDS Clinical Trials Group. The impact of sex and contraceptive therapy on the plasma and intracellular pharmacokinetics of zidovudine. AIDS 2006;20:1833–41. CrossRef PubMed
  270. Kearney BP, Mathias A. Lack of effect of tenofovir disoproxil fumarate on pharmacokinetics of hormonal contraceptives. Pharmacotherapy 2009;29:924–9. CrossRef PubMed
  271. Todd CS, Deese J, Wang M, et al. FEM-PrEP Study Group. Sino-implant (II)® continuation and effect of concomitant tenofovir disoproxil fumarate-emtricitabine use on plasma levonorgestrel concentrations among women in Bondo, Kenya. Contraception 2015;91:248–52. CrossRef PubMed
  272. Murnane PM, Heffron R, Ronald A, et al. Partners PrEP Study Team. Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception. AIDS 2014;28:1825–30. CrossRef PubMed
  273. Kasonde M, Niska RW, Rose C, et al. Bone mineral density changes among HIV-uninfected young adults in a randomised trial of pre-exposure prophylaxis with tenofovir-emtricitabine or placebo in Botswana. PLoS One 2014;9:e90111. CrossRef PubMed
  274. Callahan R, Nanda K, Kapiga S, et al. FEM-PrEP Study Group. Pregnancy and contraceptive use among women participating in the FEM-PrEP trial. J Acquir Immune Defic Syndr 2015;68:196–203. CrossRef PubMed
  275. Patel RC, Onono M, Gandhi M, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV 2015;2:e474–82. CrossRef PubMed
  276. Pyra M, Heffron R, Mugo NR, et al. ; Partners in Prevention HSV/HIV Transmission Study and Partners PrEP Study Teams. Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy. AIDS 2015;29:2353–9. CrossRef PubMed
  277. Clark RA, Theall K. Population-based study evaluating association between selected antiretroviral therapies and potential oral contraceptive failure. J Acquir Immune Defic Syndr 2004;37:1219–20. CrossRef PubMed
  278. Landolt NK, Phanuphak N, Ubolyam S, et al. Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. J Acquir Immune Defic Syndr 2013;62:534–9. CrossRef PubMed
  279. Sevinsky H, Eley T, Persson A, et al. The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women. Antivir Ther 2011;16:149–56. CrossRef PubMed
  280. Landolt NK, Phanuphak N, Ubolyam S, et al. Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women. J Acquir Immune Defic Syndr 2014;66:e50–2. PubMed
  281. Schöller-Gyüre M, Kakuda TN, Woodfall B, et al. Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Contraception 2009;80:44–52. CrossRef PubMed
  282. Myer L, Carter RJ, Katyal M, Toro P, El-Sadr WM, Abrams EJ. Impact of antiretroviral therapy on incidence of pregnancy among HIV-infected women in Sub-Saharan Africa: a cohort study. PLoS Med 2010;7:e1000229. CrossRef PubMed
  283. Nanda K, Delany-Moretlwe S, Dubé K, et al. Nevirapine-based antiretroviral therapy does not reduce oral contraceptive effectiveness. AIDS 2013;27(Suppl 1):S17–25. CrossRef PubMed
  284. Stuart GS, Moses A, Corbett A, et al. Combined oral contraceptives and antiretroviral PK/PD in Malawian women: pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi. J Acquir Immune Defic Syndr 2011;58:e40–3. CrossRef PubMed
  285. Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr 2002;29:471–7. CrossRef PubMed
  286. Muro E, Droste JA, Hofstede HT, Bosch M, Dolmans W, Burger DM. Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine: implications for intervention studies. J Acquir Immune Defic Syndr 2005;39:419–2. CrossRef PubMed
  287. Crauwels HM, van Heeswijk RP, Buelens A, Stevens M, Hoetelmans RM. Lack of an effect of rilpivirine on the pharmacokinetics of ethinylestradiol and norethindrone in healthy volunteers. Int J Clin Pharmacol Ther 2014;52:118–28. CrossRef PubMed
  288. Zhang J, Chung E, Yones C, et al. The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women. Antivir Ther 2011;16:157–64. CrossRef PubMed
  289. Sekar VJ, Lefebvre E, Guzman SS, et al. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women. Antivir Ther 2008;13:563–9. PubMed
  290. Glaxo Smith Kline. Lexiva (fosamprenavir calcium) [Package insert]. Research Triangle Park, NC: Glaxo Smith Kline; 2015.
  291. Vogler MA, Patterson K, Kamemoto L, et al. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr 2010;55:473–82. CrossRef PubMed
  292. Fröhlich M, Burhenne J, Martin-Facklam M, et al. Oral contraception does not alter single dose saquinavir pharmacokinetics in women. Br J Clin Pharmacol 2004;57:244–52 . CrossRef PubMed
  293. Boehringer Ingelheim Pharmaceuticals. Aptivus (tipranavir) [Package insert]. Ridgefield, CT; 2005.
  294. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) [Package insert]. Princeton, NJ; 2003.
  295. Abel S, Russell D, Whitlock LA, Ridgway CE, Muirhead GJ. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol 2008;65(Suppl 1):19–26. CrossRef PubMed
  296. Anderson MS, Hanley WD, Moreau AR, et al. Effect of raltegravir on estradiol and norgestimate plasma pharmacokinetics following oral contraceptive administration in healthy women. Br J Clin Pharmacol 2011;71:616–20. CrossRef PubMed
  297. Song IH, Borland J, Chen S, Wajima T, Peppercorn AF, Piscitelli SC. Dolutegravir has no effect on the pharmacokinetics of oral contraceptives with norgestimate and ethinyl estradiol. Ann Pharmacother 2015;49:784–9. CrossRef PubMed
  298. Gilead Sciences. Vitekta (elvitegravir) [Package insert]. Foster City, CA; 2012.
  299. Back DJ, Bates M, Bowden A, et al. The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy. Contraception 1980;22:495–503. CrossRef PubMed
  300. Doose DR, Wang SS, Padmanabhan M, Schwabe S, Jacobs D, Bialer M. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 2003;44:540–9. CrossRef PubMed
  301. Fattore C, Cipolla G, Gatti G, et al. Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia 1999;40:783–7. CrossRef PubMed
  302. Rosenfeld WE, Doose DR, Walker SA, Nayak RK. Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997;38:317–23. CrossRef PubMed
  303. Christensen J, Petrenaite V, Atterman J, et al. Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia 2007;48:484–9. CrossRef PubMed
  304. Contin M, Albani F, Ambrosetto G, et al. Variation in lamotrigine plasma concentrations with hormonal contraceptive monthly cycles in patients with epilepsy. Epilepsia 2006;47:1573–5. CrossRef PubMed
  305. Reimers A, Helde G, Brodtkorb E. Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia 2005;46:1414–7. CrossRef PubMed
  306. Sabers A, Buchholt JM, Uldall P, Hansen EL. Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 2001;47:151–4. CrossRef PubMed
  307. Sabers A, Ohman I, Christensen J, Tomson T. Oral contraceptives reduce lamotrigine plasma levels. Neurology 2003;61:570–1. CrossRef PubMed
  308. Back DJ, Breckenridge AM, MacIver M, et al. The effects of ampicillin on oral contraceptive steroids in women. Br J Clin Pharmacol 1982;14:43–8. CrossRef PubMed
  309. Back DJ, Grimmer SF, Orme ML, Proudlove C, Mann RD, Breckenridge AM. Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics. Br J Clin Pharmacol 1988;25:527–32. CrossRef PubMed
  310. Back DJ, Tjia J, Martin C, et al. The lack of interaction between temafloxacin and combined oral contraceptive steroids. Contraception 1991;43:317–23. CrossRef PubMed
  311. Bacon JF, Shenfield GM. Pregnancy attributable to interaction between tetracycline and oral contraceptives. BMJ 1980;280:293. CrossRef PubMed
  312. Bainton R. Interaction between antibiotic therapy and contraceptive medication. Oral Surg Oral Med Oral Pathol 1986;61:453–5. CrossRef PubMed
  313. Bollen M. Use of antibiotics when taking the oral contraceptive pill.[comment]. Aust Fam Physician 1995;24:928–9. PubMed
  314. Bromham DR, Cartmill RS. Knowledge and use of secondary contraception among patients requesting termination of pregnancy. BMJ 1993;306:556–7. CrossRef PubMed
  315. Côté J. Interaction of griseofulvin and oral contraceptives.[comment]. J Am Acad Dermatol 1990;22:124–5. CrossRef PubMed
  316. Csemiczky G, Alvendal C, Landgren BM. Risk for ovulation in women taking a low-dose oral contraceptive (Microgynon) when receiving antibacterial treatment with a fluoroquinolone (ofloxacin). Adv Contracept 1996;12:101–9. CrossRef PubMed
  317. de Groot AC, Eshuis H, Stricker BH. Inefficacy of oral contraception during use of minocycline [Dutch]. Ned Tijdschr Geneeskd 1990;134:1227–9. PubMed
  318. DeSano EA , Hurley SC. Possible interactions of antihistamines and antibiotics with oral contraceptive effectiveness. Fertil Steril 1982;37:853–4 . CrossRef PubMed
  319. Donley TG, Smith RF, Roy B. Reduced oral contraceptive effectiveness with concurrent antibiotic use: a protocol for prescribing antibiotics to women of childbearing age. Compendium 1990;11:392–6. PubMed
  320. Friedman CI, Huneke AL, Kim MH, Powell J. The effect of ampicillin on oral contraceptive effectiveness. Obstet Gynecol 1980;55:33–7. PubMed
  321. Grimmer SF, Allen WL, Back DJ, Breckenridge AM, Orme M, Tjia J. The effect of cotrimoxazole on oral contraceptive steroids in women. Contraception 1983;28:53–9. CrossRef PubMed
  322. Helms SE, Bredle DL, Zajic J, Jatjoura D, Brodell RT, Krishnarao I. Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol 1997;36:705–10. CrossRef PubMed
  323. Hempel E, Böhm W, Carol W, Klinger G. [Enzyme induction by drugs and hormonal contraception]. Zentralbl Gynakol 1973;95:1451–7. PubMed
  324. Hempel E, Zorn C, Graf K. [Effect of chemotherapy agents and antibiotics on hormonal contraception]. Z Arztl Fortbild (Jena) 1978;72:924–6. PubMed
  325. Hetényi G. Possible interactions between antibiotics and oral contraceptives. Ther Hung 1989;37:86–9. PubMed
  326. Hughes BR, Cunliffe WJ. Interactions between the oral contraceptive pill and antibiotics.[comment]. Br J Dermatol 1990;122:717–8. CrossRef PubMed
  327. Joshi JV, Joshi UM, Sankholi GM, et al. A study of interaction of low-dose combination oral contraceptive with Ampicillin and Metronidazole. Contraception 1980;22:643–52. CrossRef PubMed
  328. Kakouris H, Kovacs GT. Pill failure and nonuse of secondary precautions. Br J Fam Plann 1992;18:41–4.
  329. Kakouris H, Kovacs GT. How common are predisposing factors to pill failure among pill users? Br J Fam Plann 1994;20:33–5.
  330. Kovacs GT, Riddoch G, Duncombe P, et al. Inadvertent pregnancies in oral contraceptive users. Med J Aust 1989;150:549–51. PubMed
  331. Lequeux A. [Pregnancy under oral contraceptives after treatment with tetracycline]. Louv Med 1980;99:413–4. PubMed
  332. London BM, Lookingbill DP. Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives. Arch Dermatol 1994;130:392–3. CrossRef PubMed
  333. Maggiolo F, Puricelli G, Dottorini M, Caprioli S, Bianchi W, Suter F. The effect of ciprofloxacin on oral contraceptive steroid treatments. Drugs Exp Clin Res 1991;17:451–4. PubMed
  334. Murphy AA, Zacur HA, Charache P, Burkman RT. The effect of tetracycline on levels of oral contraceptives. Am J Obstet Gynecol 1991;164:28–33. CrossRef PubMed
  335. Neely JL, Abate M, Swinker M, D’Angio R. The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone. Obstet Gynecol 1991;77:416–20. PubMed
  336. Pillans PI, Sparrow MJ. Pregnancy associated with a combined oral contraceptive and itraconazole.[comment]. N Z Med J 1993;106:436. PubMed
  337. Scholten PC, Droppert RM, Zwinkels MG, Moesker HL, Nauta JJ, Hoepelman IM. No interaction between ciprofloxacin and an oral contraceptive. Antimicrob Agents Chemother 1998;42:3266–8. PubMed
  338. Silber TJ. Apparent oral contraceptive failure associated with antibiotic administration. J Adolesc Health Care 1983;4:287–9. CrossRef PubMed
  339. Sparrow MJ. Pill method failures. N Z Med J 1987;100:102–5. PubMed
  340. Sparrow MJ. Pregnancies in reliable pill takers. N Z Med J 1989;102:575–7. PubMed
  341. Sparrow MJ. Pill method failures in women seeking abortion: fourteen years experience. N Z Med J 1998;111:386–8. PubMed
  342. van Dijke CP, Weber JC. Interaction between oral contraceptives and griseofulvin. Br Med J (Clin Res Ed) 1984;288:1125–6. CrossRef PubMed
  343. Wermeling DP, Chandler MH, Sides GD, Collins D, Muse KN. Dirithromycin increases ethinyl estradiol clearance without allowing ovulation. Obstet Gynecol 1995;86:78–84. CrossRef PubMed
  344. Young LK, Farquhar CM, McCowan LM, Roberts HE, Taylor J. The contraceptive practices of women seeking termination of pregnancy in an Auckland clinic. N Z Med J 1994;107:189–92. PubMed
  345. Abrams LS, Skee D, Natarajan J, Wong FA. Pharmacokinetic overview of Ortho Evra/Evra. Fertil Steril 2002;77(Suppl 2):S3–12. CrossRef PubMed
  346. Dogterom P, van den Heuvel MW, Thomsen T. Absence of pharmacokinetic interactions of the combined contraceptive vaginal ring NuvaRing with oral amoxicillin or doxycycline in two randomised trials. Clin Pharmacokinet 2005;44:429–38. CrossRef PubMed
  347. Devenport MH, Crook D, Wynn V, Lees LJ. Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives. Br J Clin Pharmacol 1989;27:851–9. CrossRef PubMed
  348. Hilbert J, Messig M, Kuye O, Friedman H. Evaluation of interaction between fluconazole and an oral contraceptive in healthy women. Obstet Gynecol 2001;98:218–23. PubMed
  349. Kovács I, Somos P, Hámori M. Examination of the potential interaction between ketoconazole (Nizoral) and oral contraceptives with special regard to products of low hormone content (Rigevidon, anteovin). Ther Hung 1986;34:167–70. PubMed
  350. Lunell NO, Pschera H, Zador G, Carlström K. Evaluation of the possible interaction of the antifungal triazole SCH 39304 with oral contraceptives in normal healthy women. Gynecol Obstet Invest 1991;32:91–7. CrossRef PubMed
  351. McDaniel PA, Caldroney RD. Oral contraceptives and griseofulvin interactions. Drug Intell Clin Pharm 1986;20:384. PubMed
  352. Meyboom RH, van Puijenbroek EP, Vinks MH, Lastdrager CJ. Disturbance of withdrawal bleeding during concomitant use of itraconazole and oral contraceptives. N Z Med J 1997;110:300. PubMed
  353. Rieth H, Sauerbrey N. [Interaction studies with fluconazole, a new triazole antifungal drug]. Wien Med Wochenschr 1989;139:370–4. PubMed
  354. Sinofsky FE, Pasquale SA. The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives. Am J Obstet Gynecol 1998;178:300–4. CrossRef PubMed
  355. van Puijenbroek EP, Feenstra J, Meyboom RH. [Pill cycle disturbance in simultaneous use of itraconazole and oral contraceptives]. Ned Tijdschr Geneeskd 1998;142:146–9. PubMed
  356. Van Puijenbroek EP, Egberts AC, Meyboom RH, Leufkens HG. Signalling possible drug-drug interactions in a spontaneous reporting system: delay of withdrawal bleeding during concomitant use of oral contraceptives and itraconazole. Br J Clin Pharmacol 1999;47:689–93. CrossRef PubMed
  357. Verhoeven CH, van den Heuvel MW, Mulders TM, Dieben TO. The contraceptive vaginal ring, NuvaRing, and antimycotic co-medication. Contraception 2004;69:129–32. CrossRef PubMed
  358. Back DJ, Breckenridge AM, Grimmer SF, Orme ML, Purba HS. Pharmacokinetics of oral contraceptive steroids following the administration of the antimalarial drugs primaquine and chloroquine. Contraception 1984;30:289–95. CrossRef PubMed
  359. Croft AM, Herxheimer A. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement? BMC Public Health 2002;2:6. CrossRef PubMed
  360. Karbwang J, Looareesuwan S, Back DJ, Migasana S, Bunnag D, Breckenridge AM. Effect of oral contraceptive steroids on the clinical course of malaria infection and on the pharmacokinetics of mefloquine in Thai women. Bull World Health Organ 1988;66:763–7. PubMed
  361. McGready R, Stepniewska K, Seaton E, et al. Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Eur J Clin Pharmacol 2003;59:553–7. CrossRef PubMed
  362. Wanwimolruk S, Kaewvichit S, Tanthayaphinant O, Suwannarach C, Oranratnachai A. Lack of effect of oral contraceptive use on the pharmacokinetics of quinine. Br J Clin Pharmacol 1991;31:179–81. CrossRef PubMed
  363. Back DJ, Breckenridge AM, Crawford F, et al. The effect of rifampicin on norethisterone pharmacokinetics. Eur J Clin Pharmacol 1979;15:193–7. CrossRef PubMed
  364. Back DJ, Breckenridge AM, Crawford FE, et al. The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women. Contraception 1980;21:135–43. CrossRef PubMed
  365. Barditch-Crovo P, Trapnell CB, Ette E, et al. The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive. Clin Pharmacol Ther 1999;65:428–38. CrossRef PubMed
  366. Bolt HM, Bolt M, Kappus H. Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man. Acta Endocrinol (Copenh) 1977;85:189–97. PubMed
  367. Gupta KC, Ali MY. Failure of oral contraceptive with rifampicin. Med J Zambia 1980;15:23. PubMed
  368. Hirsch A. [Letter: Sleeping pills]. Nouv Presse Med 1973;2:2957. PubMed
  369. Hirsch A, Tillement JP, Chretien J. Effets contrariants de la rifampicine sur les contraceptifs oraux: a propos de trois grossesses non desiree chez trois malades. Rev Fr Mal Respir 1975;2:174–82.
  370. Joshi JV, Joshi UM, Sankolli GM, et al. A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs. Contraception 1980;21:617–29. CrossRef PubMed
  371. Kropp R. [Rifampicin and oral contraceptives (author’s transl)]. Prax Pneumol 1974;28:270–2. PubMed
  372. LeBel M, Masson E, Guilbert E, et al. Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone. J Clin Pharmacol 1998;38:1042–50. CrossRef PubMed
  373. Meyer B, Müller F, Wessels P, Maree J. A model to detect interactions between roxithromycin and oral contraceptives. Clin Pharmacol Ther 1990;47:671–4. CrossRef PubMed
  374. Nocke-Finck L, Breuer H, Reimers D. Dtsch Med Wochenschr 1973;98:1521–3. CrossRef PubMed
  375. Piguet B, Muglioni JF, Chaline G. [Letter: Oral contraception and rifampicin]. Nouv Presse Med 1975;04:115–6. PubMed
  376. Reimers D, Jezek A. [The simultaneous use of rifampicin and other antitubercular agents with oral contraceptives]. Prax Pneumol 1971;25:255–62. PubMed
  377. Skolnick JL, Stoler BS, Katz DB, Anderson WH. Rifampin, oral contraceptives, and pregnancy. JAMA 1976;236:1382. CrossRef PubMed
  378. Szoka PR, Edgren RA. Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database. Fertil Steril 1988;49(Suppl 2):31S–8S. PubMed
  379. Berry-Bibee E, Kim MJ, Simmons K, Pagano P, Curtis K. Drug interactions between hormonal contraceptives and psychotropic drugs: a systematic review. Contraception . In press 2016.
  380. Berry-Bibee E, Kim MJ, Tepper N, Riley H, Curtis K. The safety of St John’s wort and hormonal contraceptives: a systematic review. Contraception. In press 2016.

Appendix E

Classifications for Barrier Methods

Classifications for barrier contraceptive methods include those for condoms, which include male latex condoms, male polyurethane condoms, and female condoms; spermicides; and diaphragm with spermicide or cervical cap ( Box E1) ( Table E1).

Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention might not be appropriate for those who cannot use them consistently and correctly because of the relatively higher typical-use failure rates of these methods. Women should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs). Use of female condoms can provide protection from transmission of STDs, although data are limited.

Return to your place in the textBOX E1. Categories for classifying barrier methods

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE E1. Classifications for barrier methods, including condoms, spermicides, diaphragms (with spermicide), and cap
Condition Category Clarifications/Evidence/Comments
Condom Spermicide Diaphragm (with spermicide)/Cap
Personal Characteristics and Reproductive History
Pregnancy NA NA NA Clarification: None of these methods are relevant for contraception during known pregnancy. However, for women who remain at risk for STDs/HIV during pregnancy, the correct and consistent use of condoms is recommended.
Age
a. Menarche to <40 years 1 1 1
b. =40 years 1 1 1
Parity
a. Nulliparous 1 1 1
b. Parous 1 1 2 Clarification: Risk for cervical cap failure is higher in parous women than in nulliparous women.
Postpartum (breastfeeding and nonbreastfeeding)
a. <6 weeks postpartum 1 1 NA Clarification: Diaphragm and cap are unsuitable until uterine involution is complete.
b. =6 weeks postpartum 1 1 1
Postabortion
a. First trimester 1 1 1
b. Second trimester 1 1 1 Clarification: Diaphragm and cap are unsuitable until 6 weeks after second trimester abortion.
c. Immediate postseptic abortion 1 1 1
Past ectopic pregnancy 1 1 1
History of pelvic surgery 1 1 1
Smoking
a. Age <35 years 1 1 1
b. Age =35 years
  i. <15 cigarettes per day 1 1 1
  ii. =15 cigarettes per day 1 1 1
Obesity Comment: Severe obesity might make diaphragm and cap placement difficult.
a. BMI =30 kg/m2 1 1 1
b. Menarche to <18 years and BMI =30 kg/m2 1 1 1
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 1 1
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) 1 1 1
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels) 1 1 1
Hypertension
Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension 1 1 1
b. Elevated blood pressure levels
(properly taken measurements)
  i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg 1 1 1
  ii. Systolic =160 mm Hg or diastolic =100 mm Hg 1 1 1
c. Vascular disease 1 1 1
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal) 1 1 1
Deep venous thrombosis/Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
  i. Higher risk for recurrent DVT/PE (one or more risk factors) 1 1 1
     • History of estrogen-associated DVT/PE
• Pregnancy-associated DVT/PE
• Idiopathic DVT/PE
• Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
  ii. Lower risk for recurrent DVT/PE (no risk factors) 1 1 1
b. Acute DVT/PE 1 1 1
c. DVT/PE and established anticoagulant therapy for at least 3 months
  i. Higher risk for recurrent DVT/PE (one or more risk factors) 1 1 1
     • Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
  ii. Lower risk for recurrent DVT/PE (no risk factors) 1 1 1
d. Family history (first-degree relatives) 1 1 1
e. Major surgery
  i. With prolonged immobilization 1 1 1
  ii. Without prolonged immobilization 1 1 1
f. Minor surgery without immobilization 1 1 1
Known thrombogenic mutations (e.g., factor V Leiden; prothrombin mutation; or protein S, protein C, and antithrombin deficiencies)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1 Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost of screening.
Superficial venous disorders
a. Varicose veins 1 1 1
b. Superficial venous thrombosis (acute or history) 1 1 1
Current and history of ischemic heart disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Stroke (history of cerebrovascular accident)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Valvular heart disease
Complicated valvular heart disease is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 1 1 1
b. Complicated (pulmonary hypertension, risk for atrial fibrillation, or history of subacute bacterial endocarditis) 1 1 2
Peripartum cardiomyopathy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (1)
  i. <6 months 1 1 1
  ii. =6 months 1 1 1
b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (1) 1 1 1
Rheumatic Diseases
Systemic lupus erythematosus
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Positive (or unknown) antiphospholipid antibodies 1 1 1
b. Severe thrombocytopenia 1 1 1
c. Immunosuppressive therapy 1 1 1
d. None of the above 1 1 1
Rheumatoid arthritis
a. Receiving immunosuppressive therapy 1 1 1
b. Not receiving immunosuppressive therapy 1 1 1
Neurologic Conditions
Headaches
a. Nonmigraine (mild or severe) 1 1 1
b. Migraine
  i. Without aura (This category of migraine includes menstrual migraine.) 1 1 1 Comment: Menstrual migraine is a subtype of migraine without aura. For more information see The International Headache Society Classification, 3rd edition (http://www.ihs-classification.org/_downloads/mixed/International-Headache-Classification-III-ICHD-III-2013-Beta.pdf).
  ii. With aura 1 1 1
Epilepsy
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Multiple sclerosis
a. With prolonged immobility 1 1 1
b. Without prolonged immobility 1 1 1
Depressive Disorders
Depressive disorders 1 1 1
Reproductive Tract Infections and Disorders
Unexplained vaginal bleeding
(suspicious for serious condition) before evaluation
1 1 1 Clarification: If pregnancy or an underlying pathological condition (e.g., pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation.
Endometriosis 1 1 1
Benign ovarian tumors (including cysts) 1 1 1
Severe dysmenorrhea 1 1 1
Gestational trophoblastic disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Suspected gestational trophoblastic disease (immediate postevacuation)
  i. Uterine size first trimester 1 1 1
  ii. Uterine size second trimester 1 1 1
b. Confirmed gestational trophoblastic disease (after initial evacuation and during monitoring)
  i. Undetectable/nonpregnant ß–hCG levels 1 1 1
  ii. Decreasing ß–hCG levels 1 1 1
  iii. Persistently elevated ß-hCG levels or malignant disease, with no evidence or suspicion of intrauterine disease 1 1 1
  iv. Persistently elevated ß-hCG levels or malignant disease, with evidence or suspicion of intrauterine disease 1 1 1
Cervical ectropion 1 1 1
Cervical intraepithelial neoplasia 1 1 1 Clarification: The cap should not be used. Diaphragm use has no restrictions.
Cervical cancer (awaiting treatment) 1 2 1 Clarification: The cap should not be used. Diaphragm use has no restrictions.
Comment: Repeated and high-dose use of the spermicide nonoxynol-9 can cause vaginal and cervical irritation or abrasions.
Breast disease
Breast cancer is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Undiagnosed mass 1 1 1
b. Benign breast disease 1 1 1
c. Family history of cancer 1 1 1
d. Breast cancer
  i. Current 1 1 1
  ii. Past and no evidence of current disease for 5 years 1 1 1
Endometrial hyperplasia 1 1 1
Endometrial cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Ovarian cancer
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Uterine fibroids 1 1 1
Anatomical abnormalities 1 1 NA Clarification: The diaphragm cannot be used in certain cases of prolapse. Cap use is not appropriate for a woman with markedly distorted cervical anatomy.
Pelvic inflammatory disease
a. Past PID
  i. With subsequent pregnancy 1 1 1
  ii. Without subsequent pregnancy 1 1 1
b. Current PID 1 1 1
Sexually transmitted diseases
a. Current purulent cervicitis or chlamydial infection or gonococcal infection 1 1 1
b. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) 1 1 1
c. Other factors related to STDs 1 1 1
HIV
High risk for HIV 1 4 4 Evidence: Repeated and high-dose use of the spermicide nonoxynol-9 was associated with increased risk for genital lesions, which might increase the risk for HIV infection (2).
Comment: Diaphragm use is assigned category 4 because of concerns about the spermicide, not the diaphragm.
HIV infection
For women with HIV infection who are not clinically well or not receiving ARV therapy, this condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 3 3 Comment: Use of spermicides or diaphragms (with spermicide) can disrupt the cervical mucosa, which might increase viral shedding and HIV transmission to noninfected sex partners.
Other Infections
Schistosomiasis
Schistosomiasis with fibrosis of the liver is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Uncomplicated 1 1 1
b. Fibrosis of the liver 1 1 1
Tuberculosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Nonpelvic 1 1 1
b. Pelvic 1 1 1
Malaria 1 1 1
History of toxic shock syndrome 1 1 3 Comment: Toxic shock syndrome has been reported in association with contraceptive sponge and diaphragm use.
Urinary tract infection 1 1 2 Comment: Use of diaphragms and spermicides might increase risk for urinary tract infection.
Endocrine Conditions
Diabetes
Insulin-dependent diabetes; diabetes with nephropathy, retinopathy, or neuropathy; diabetes with other vascular disease; or diabetes of >20 years’ duration are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. History of gestational disease 1 1 1
b. Nonvascular disease
  i. Non-insulin dependent 1 1 1
  ii. Insulin dependent 1 1 1
c. Nephropathy, retinopathy, or neuropathy 1 1 1
d. Other vascular disease or diabetes of >20 years’ duration 1 1 1
Thyroid disorders
a. Simple goiter 1 1 1
b. Hyperthyroid 1 1 1
c. Hypothyroid 1 1 1
Gastrointestinal Conditions
Inflammatory bowel disease
(ulcerative colitis or Crohn’s disease)
1 1 1
Gallbladder disease
a. Symptomatic
  i. Treated by cholecystectomy 1 1 1
  ii. Medically treated 1 1 1
  iii. Current 1 1 1
b. Asymptomatic 1 1 1
History of cholestasis
a. Pregnancy related 1 1 1
b. Past COC related 1 1 1
Viral hepatitis
a. Acute or flare 1 1 1
b. Carrier 1 1 1
c. Chronic 1 1 1
Cirrhosis
Severe cirrhosis is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Mild (compensated) 1 1 1
b. Severe (decompensated) 1 1 1
Liver tumors
Hepatocellular adenoma and malignant liver tumors are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Benign
  i. Focal nodular hyperplasia 1 1 1
  ii. Hepatocellular adenoma 1 1 1
b. Malignant (hepatoma) 1 1 1
Respiratory Conditions
Cystic fibrosis
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Anemias
Thalassemia 1 1 1
Sickle cell disease
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 1 1
Iron deficiency anemia 1 1 1
Solid Organ Transplantation
Solid organ transplantation
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy 1 1 1
b. Uncomplicated 1 1 1
Drug Interactions
Antiretroviral therapy Clarification: No drug interaction between ARV therapy and barrier method use is known. However, HIV infection is classified as category 3 for spermicides and diaphragms (see HIV section).
a. Nucleoside reverse transcriptase inhibitors (NRTIs)
  i. Abacavir (ABC) 1 3 3
  ii. Tenofovir (TDF) 1 3 3
  iii. Zidovudine (AZT) 1 3 3
  iv. Lamivudine (3TC) 1 3 3
  v. Didanosine (DDI) 1 3 3
  vi. Emtricitabine (FTC) 1 3 3
  vii. Stavudine (D4T) 1 3 3
b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
  i. Efavirenz (EFV) 1 3 3
  ii. Etravirine (ETR) 1 3 3
  iii. Nevirapine (NVP) 1 3 3
  iv. Rilpivirine (RPV) 1 3 3
c. Ritonavir-boosted protease inhibitors
  i. Ritonavir-boosted atazanavir (ATV/r) 1 3 3
  ii. Ritonavir-boosted darunavir (DRV/r) 1 3 3
  iii. Ritonavir-boosted fosamprenavir (FPV/r) 1 3 3
  iv. Ritonavir-boosted lopinavir (LPV/r) 1 3 3
  v. Ritonavir-boosted saquinavir (SQV/r) 1 3 3
  vi. Ritonavir-boosted tipranavir (TPV/r) 1 3 3
d. Protease inhibitors without ritonavir
  i. Atazanavir (ATV) 1 3 3
  ii. Fosamprenavir (FPV) 1 3 3
  iii. Indinavir (IDV) 1 3 3
  iv. Nelfinavir (NFV) 1 3 3
e. CCR5 co-receptor antagonists
  i. Maraviroc (MVC) 1 3 3
f. HIV integrase strand transfer inhibitors
  i. Raltegravir (RAL) 1 3 3
  ii. Dolutegravir (DTG) 1 3 3
  iii. Elvitegravir (EVG) 1 3 3
g. Fusion inhibitors
  i. Enfuvirtide 1 3 3
Anticonvulsant therapy
a. Certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, or oxcarbazepine) 1 1 1
b. Lamotrigine 1 1 1
Antimicrobial therapy
a. Broad-spectrum antibiotics 1 1 1
b. Antifungals 1 1 1
c. Antiparasitics 1 1 1
d. Rifampin or rifabutin therapy 1 1 1
Psychotropic medications
a. SSRIs 1 1 1
St. John’s wort 1 1 1
Allergy to latex 3 1 3 Clarification: The condition of allergy to latex does not apply to plastic condoms/diaphragms.

Abbreviations: ARV = antiretroviral; BMI = body mass index; COC = combined oral contraceptive; DVT = deep venous thrombosis; hCG = human chorionic gonadotropin; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; LDL = low-density lipoprotein; NA = not applicable; PE = pulmonary embolism; PID = pelvic inflammatory disease; SSRI = selective serotonin reuptake inhibitor; STD = sexually transmitted disease.

References

  1. The Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Little, Brown and Co; 1994.
  2. Wilkinson D, Ramjee G, Tholandi M, Rutherford G. Nonoxynol-9 for preventing vaginal acquisition of HIV infection by women from men. Cochrane Database Syst Rev 2002;4(CD003936):CD003936. PubMed

Appendix F

Classifications for Fertility Awareness–Based Methods

Fertility awareness–based (FAB) methods of family planning involve identifying the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature or by monitoring cycle days ( Box F1) ( Table F1). FAB methods can be used in combination with abstinence or barrier methods during the fertile time. If barrier methods are used, see the Classifications for Barrier Methods (Appendix E).

No medical conditions worsen because of FAB methods. In general, FAB methods can be used without concern for health effects in persons who choose them. However, several conditions make their use more complex. The existence of these conditions suggests that 1) use of these methods should be delayed until the condition is corrected or resolved, or 2) persons using FAB methods need special counseling, and a provider with particular training in use of these methods is generally necessary to ensure correct use.

Women with conditions that make pregnancy an unacceptable risk should be advised that FAB methods might not be appropriate for them because of the relatively higher typical-use failure rates of these methods. Symptoms-based and calendar-based methods do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Return to your place in the textBOX F1. Definitions for terms associated with fertility awareness–based methods
  • Symptoms-based methods: FAB methods based on observation of fertility signs (e.g., cervical secretions or basal body temperature) such as the cervical mucus method, the symptothermal method, and the TwoDay method.
  • Calendar-based methods: FAB methods based on calendar calculations such as the calendar rhythm method and the standard days method.
  • Accept: No medical reason exists to deny the particular FAB method to a woman in this circumstance.
  • Caution: The method normally is provided in a routine setting but with extra preparation and precautions. For FAB methods, this usually means that special counseling might be needed to ensure correct use of the method by a woman in this circumstance.
  • Delay: Use of this method should be delayed until the condition is evaluated or corrected. Alternative temporary methods of contraception should be offered.

Abbreviation: FAB = fertility awareness–based.

Return to your place in the textTABLE F1. Fertility awareness–based methods, including symptoms-based and calendar-based methods
Condition Category Clarifications/Evidence/Comments
Symptoms-based method Calendar-based method
Personal Characteristics and Reproductive History
Pregnancy NA NA Clarification: FAB methods are not relevant during pregnancy.
Life stage Comment: Menstrual irregularities are common in postmenarche and perimenopause and might complicate the use of FAB methods.
a. Postmenarche Caution Caution
b. Perimenopause Caution Caution
Breastfeeding Comment: Use of FAB methods when breastfeeding might be less effective than when not breastfeeding.
a. <6 weeks postpartum Delay Delay Comment: Women who are primarily breastfeeding and are amenorrheic are unlikely to have sufficient ovarian function to produce detectable fertility signs and hormonal changes during the first 6 months postpartum. However, the likelihood of resumption of fertility increases with time postpartum and with substitution of breast milk by other foods.
b. =6 weeks Caution Delay
c. After menses begin Caution Caution Clarification: When the woman notices fertility signs, particularly cervical secretions, she can use a symptoms-based method. First postpartum menstrual cycles in breastfeeding women vary significantly in length. Return to regularity takes several cycles. When she has had at least three postpartum menses and her cycles are regular again, she can use a calendar-based method. When she has had at least four postpartum menses and her most recent cycle lasted 26–32 days, she can use the standard days method. Before that time, a barrier method should be offered if the woman plans to use a FAB method later.
Postpartum (nonbreastfeeding women)
a. <4 weeks Delay Delay Clarification: Nonbreastfeeding women are not likely to have detectable fertility signs or hormonal changes before 4 weeks postpartum. Although the risk for pregnancy is low, ovulation before first menses is common; therefore, a method appropriate for the postpartum period should be offered.
b. =4 weeks Accept Delay Clarification: Nonbreastfeeding women are likely to have sufficient ovarian function to produce detectable fertility signs, hormonal changes, or both at this time; likelihood increases rapidly with time postpartum. Women can use calendar-based methods as soon as they have completed three postpartum menses. Methods appropriate for the postpartum period should be offered before that time.
Postabortion Caution Delay Clarification: After abortion, women are likely to have sufficient ovarian function to produce detectable fertility signs, hormonal changes, or both; likelihood increases with time postabortion. Women can start using calendar-based methods after they have had at least one postabortion menses (e.g., women who before this pregnancy primarily had cycles of 26–32 days can then use the standard days method). Methods appropriate for the postabortion period should be offered before that time.
Reproductive Tract Infections and Disorders
Irregular vaginal bleeding Delay Delay Clarification: Presence of this condition makes FAB methods unreliable. Therefore, barrier methods should be recommended until the bleeding pattern is compatible with proper method use. The condition should be evaluated and treated as necessary.
Vaginal discharge Delay Accept Clarification: Because vaginal discharge makes recognition of cervical secretions difficult, the condition should be evaluated and treated if needed before providing methods based on cervical secretions.
Other
Use of drugs that affect cycle regularity, hormones, or fertility signs Caution /Delay Caution/Delay Clarification: Use of certain mood-altering drugs such as lithium, tricyclic antidepressants, and antianxiety therapies, as well as certain antibiotics and anti-inflammatory drugs, might alter cycle regularity or affect fertility signs. The condition should be carefully evaluated and a barrier method offered until the degree of effect has been determined or the drug is no longer being used.
Diseases that elevate body temperature
a. Chronic diseases Caution Accept Clarification: Elevated temperatures might make basal body temperature difficult to interpret but have no effect on cervical secretions. Thus, use of a method that relies on temperature should be delayed until the acute febrile disease abates. Temperature-based methods are not appropriate for women with chronically elevated temperatures. In addition, some chronic diseases interfere with cycle regularity, making calendar-based methods difficult to interpret.
b. Acute diseases Delay Accept

Abbreviations: FAB = fertility awareness–based; NA = not applicable.

Appendix G

Lactational Amenorrhea Method

The Bellagio Consensus provided the scientific basis for defining the conditions under which breastfeeding can be used safely and effectively for birth-spacing purposes; programmatic guidelines were developed at a meeting of family planning experts for its use as a method of family planning, and the method was then given the name the lactational amenorrhea method (1,2). These guidelines include the following three criteria, all of which must be met to ensure adequate protection from an unplanned pregnancy: 1) amenorrhea; 2) fully or nearly fully breastfeeding (no interval of >4–6 hours between breastfeeds); and 3) <6 months postpartum.

All major medical organizations recommend exclusive breastfeeding for the first 6 months of life, with continuing breastfeeding through the first year and beyond for as long as mutually desired (3). No medical conditions exist for which use of the lactational amenorrhea method for contraception is restricted. However, breastfeeding might not be recommended for women or infants with certain conditions.

Women with conditions that make pregnancy an unacceptable risk should be advised that the lactational amenorrhea method might not be appropriate for them because of its relatively higher typical-use failure rates. The lactational amenorrhea method does not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using this method should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

HIV Infection

HIV can be transmitted from mother to infant through breastfeeding. Therefore, in the United States, where replacement feeding is affordable, feasible, acceptable, sustainable, and safe, breastfeeding for women with HIV is not recommended (3,4).

Other Medical Conditions

The American Academy of Pediatrics (AAP) also recommends against breastfeeding for women with active untreated tuberculosis disease, untreated brucellosis, varicella, H1N1 influenza, or positivity for human T-cell lymphotropic virus types I or II or for those who have herpes simplex lesions on a breast. In addition, infants with classic galactosemia should not breastfeed (3).

Medication Used During Breastfeeding

AAP recommends that the benefits of breastfeeding outweigh the risk of exposure to most therapeutic agents via human milk. More information about specific drugs and radioactive compounds is provided by AAP (5) and LactMed (http://toxnet.nlm.nih.gov).

References

  1. Kennedy KI, Rivera R, McNeilly AS. Consensus statement on the use of breastfeeding as a family planning method. Contraception 1989;39:477–96. CrossRef PubMed
  2. Labbok M, Cooney K, Coly S. Guidelines: breastfeeding, family planning, and the Lactational Amenorrhea Method-LAM. Washington, DC: Institute for Reproductive Health; 1994.
  3. American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of human milk [Policy statement]. Pediatrics 2012;129:e827–41. CrossRef PubMed
  4. Perinatal HIV Guidelines Working Group. Public Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Rockville, MD: Public Health Service Task Force; 2009.
  5. Sachs HC; Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics 2013;132:e796–809. CrossRef PubMed

Appendix H

Coitus Interruptus (Withdrawal)

Coitus interruptus, also known as withdrawal, is a traditional family planning method in which the man completely removes his penis from the vagina and away from the external genitalia of the female partner before he ejaculates. Coitus interruptus prevents sperm from entering the woman’s vagina, thereby preventing contact between spermatozoa and the ovum.

This method might be appropriate for couples

  • who are highly motivated and able to use this method effectively;
  • with religious or philosophical reasons for not using other methods of contraception;
  • who need contraception immediately and have entered into a sexual act without alternative methods available;
  • who need a temporary method while awaiting the start of another method; or
  • who have intercourse infrequently.

Some benefits of coitus interruptus are that the method, if used correctly, does not affect breastfeeding and is always available for primary use or use as a back-up method. In addition, coitus interruptus involves no economic cost or use of chemicals and has no directly associated health risks. Coitus interruptus does not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using this method should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Coitus interruptus is unforgiving of incorrect use, and its effectiveness depends on the willingness and ability of the couple to use withdrawal with every act of intercourse. Women with conditions that make pregnancy an unacceptable risk should be advised that coitus interruptus might not be appropriate for them because of its relatively higher typical-use failure rates.

Appendix I

Female and Male Sterilization

Tubal sterilization for women and vasectomy for men are permanent, safe, and highly effective methods of contraception. In general, no medical conditions absolutely restrict a person’s eligibility for sterilization (with the exception of known allergy or hypersensitivity to any materials used to complete the sterilization method). However, certain conditions place a woman at high surgical risk; in these cases, careful consideration should be given to the risks and benefits of other acceptable alternatives, including long-acting, highly effective, reversible methods and vasectomy. Female and male sterilization do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Because these methods are intended to be irreversible, persons who choose sterilization should be certain that they want to prevent pregnancy permanently. Most persons who choose sterilization remain satisfied with their decision. However, a small proportion of women regret this decision (1%–26% from different studies, with higher rates of regret reported by women who were younger at sterilization) (1,2). Regret among men about vasectomy has been reported to be approximately 5% (3), similar to the proportion of women who report regretting their husbands’ vasectomy (6%) (4). Therefore, all persons should be appropriately counseled about the permanency of sterilization and the availability of highly effective, reversible methods of contraception.

References

  1. Hillis SD, Marchbanks PA, Tylor LR, Peterson HB. Poststerilization regret: findings from the United States Collaborative Review of Sterilization. Obstet Gynecol 1999;93:889–95. PubMed
  2. Peterson HB. Sterilization. Obstet Gynecol 2008;111:189–203. CrossRef PubMed
  3. Ehn BE, Liljestrand J. A long-term follow-up of 108 vasectomized men. Good counselling routines are important. Scand J Urol Nephrol 1995;29:477–81. CrossRef PubMed
  4. Jamieson DJ, Kaufman SC, Costello C, Hillis SD, Marchbanks PA, Peterson HB; US Collaborative Review of Sterilization Working Group. A comparison of women’s regret after vasectomy versus tubal sterilization. Obstet Gynecol 2002;99:1073–9. PubMed

Appendix J

Classifications for Emergency Contraception

A copper-containing intrauterine device (Cu-IUD) can be used within 5 days of unprotected intercourse as an emergency contraceptive. However, when the time of ovulation can be estimated, the Cu-IUD can be inserted beyond 5 days after intercourse, if necessary, as long as the insertion does not occur >5 days after ovulation. The eligibility criteria for interval Cu-IUD insertion also apply for the insertion of Cu-IUDs as emergency contraception ( Box J1) ( Table J1).

Classifications for emergency contraceptive pills (ECPs) are given for ulipristal acetate (UPA), levonorgestrel (LNG), and combined oral contraceptives (COCs). Cu-IUDs, UPA, LNG, and COCs do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Return to your place in the textBOX J1. Categories for classifying emergency contraception

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE J1. Classifications for emergency contraception, including the copper-containing intrauterine device, ulipristal acetate, levonorgestrel, and combined oral contraceptives
Condition Category Clarifications/Evidence/Comments
Cu-IUD UPA LNG COC
Personal Characteristics and Reproductive History
Pregnancy 4 NA NA NA Clarification (IUD): The IUD is not indicated during pregnancy and should not be used because of the risk for serious pelvic infection and septic spontaneous abortion.
Clarification (ECPs): Although this method is not indicated for a woman with a known or suspected pregnancy, no harm to the woman, the course of her pregnancy, or the fetus if ECPs are inadvertently used is known to exist.
Evidence: Evidence suggests that poor pregnancy outcomes are rare among pregnant women who used ECPs during conception cycle or early in pregnancy (1).
Breastfeeding 1 1 1 1 Clarification (UPA): Breastfeeding is not recommended for 24 hours after taking UPA because it is excreted in breast milk, with highest concentrations in the first 24 hours, and maximum maternal serum levels are reached 1–3 hours after administration. Mean UPA concentrations in breast milk decrease markedly from 0 to 24–48 hours and then slowly decrease over 5 days (2). Breast milk should be expressed and discarded for 24 hours after taking UPA.
Evidence: Breastfeeding outcomes do not seem to differ between women exposed to LNG and those who are not exposed. One pharmacokinetic study demonstrated that LNG passes to breast milk but in minimal quantities (1).
Past ectopic pregnancy 1 1 1 1
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 1 1 1
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) 1 1 1 1 Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to decrease oral contraceptive effectiveness, perhaps further decreased by postoperative complications such as long-term diarrhea, vomiting, or both. Because of these malabsorptive concerns, an emergency IUD might be more appropriate than ECPs.
Cardiovascular Disease
History of severe cardiovascular disease (ischemic heart disease, cerebrovascular attack, or other thromboembolic conditions)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 2 2 Comment: The duration of ECP use is less than that of regular use of COCs or POPs and thus would be expected to have less clinical impact.
Rheumatic Diseases
Rheumatoid arthritis
a. Receiving immunosuppressive therapy 2 1 1 1
b. Not receiving immunosuppressive therapy 1 1 1 1
Neurologic Conditions
Migraine 1 1 1 2 Comment: The duration of ECP use is less than that of regular use of COCs and thus would be expected to have less clinical impact.
Gastrointestinal Conditions
Inflammatory bowel disease (ulcerative colitis or Crohn’s disease) 1 1 1 1
Severe liver disease (including jaundice)
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
1 2 2 2 Comment: The duration of ECP use is less than that of regular use of COCs or POPs and thus would be expected to have less clinical impact.
Solid Organ Transplantation
Solid organ transplantation
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Complicated: graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy 3 1 1 1
b. Uncomplicated 2 1 1 1
Other
Repeated ECP use 1 1 1 1 Clarification: Recurrent ECP use is an indication that the woman requires further counseling about other contraceptive options. Frequently repeated ECP use might be harmful for women with conditions classified as 2, 3, or 4 for CHC or POC use.
Evidence: In one case-control study, risk for ectopic pregnancy compared with intrauterine pregnancy did not increase after repeated use of LNG ECPs compared with nonuse (1).
Sexual assault 2 1 1 1 Clarification (IUD): Women who have experienced sexual assault are at increased risk for STDs. According to CDC STD treatment guidelines, routine presumptive treatment of chlamydia, gonorrhea, and trichomonas is recommended after sexual assault (3). Women with current purulent cervicitis or chlamydial infection or gonococcal infection should not undergo IUD insertion (category 4).
Obesity (BMI =30 kg/m2) 1 2 2 2 Clarification (ECPs): ECPs might be less effective among women with BMI =30 kg/m2 than among women with BMI <25 kg/m2. Despite this, no safety concerns exist.
Evidence: Limited evidence from secondary data analyses suggests that women with BMI =30 kg/m2 experience an increased risk for pregnancy after use of LNG compared with women with BMI <25 kg/m2. Two analyses suggest obese women might also experience an increased risk for pregnancy after use of UPA compared with nonobese women, although this increase was not significant in one study (4).
CYP3A4 inducers (e.g., bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John’s wort, topiramate, efavirenz, and lumacaftor) 1 2 2 2 Clarification (ECPs): Strong CYP3A4 inducers might reduce the effectiveness of ECPs.
Evidence: According to labelling information, rifampin markedly decreases UPA levels by =90%, which might decrease its efficacy (2). Therefore, theoretical concerns extend to use of other CYP3A4 inducers as well as to COC and LNG ECPs, which have metabolic pathways similar to those of UPA. A small pharmacokinetic study found that concomitant efavirenz use decreased LNG levels in women taking LNG ECPs (0.75 mg) by 56% compared with LNG ECPs alone (5).

Abbreviations: BMI = body mass index; CHC = combined hormonal contraceptive; COC = combined hormonal contraceptive; Cu-IUD = copper-containing intrauterine device; ECP = emergency contraceptive pill; HIV = human immunodeficiency virus; IUD = intrauterine device; LNG = levonorgestrel; NA = not applicable; POC = progestin-only contraceptive; POP = progestin-only pill; STD = sexually transmitted disease; UPA = ulipristal acetate.

References

  1. Jatlaoui TC, Riley H, Curtis KM. Safety data for levonorgestrel, ulipristal acetate and Yuzpe regimens for emergency contraception. Contraception 2016;93:93–112. CrossRef PubMed
  2. Watson Pharmaceuticals. Ella [Prescribing information]. Morristown, NJ; 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022474s000lbl.pdf
  3. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-03). PubMed
  4. Jatlaoui T, Curtis KM. Safety and effectiveness data for emergency contraceptive pills among women with obesity: a systematic review. Contraception 2016. Epub May 24, 2016. CrossRef
  5. Carten ML, Kiser JJ, Kwara A, Mawhinney S, Cu-Uvin S. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and efavirenz. Infect Dis Obstet Gynecol 2012;2012:137192.

Appendix K

Summary of Classifications for Hormonal Contraceptive Methods and Intrauterine Devices

Health-care providers can use the summary table as a quick reference guide to the classifications for hormonal contraceptive methods and intrauterine contraception to compare classifications across these methods ( Box K1) ( Table K1). See the respective appendix for each method for clarifications to the numeric categories, as well as for summaries of the evidence and additional comments. Hormonal contraceptives and intrauterine devices do not protect against sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and women using these methods should be counseled that consistent and correct use of the male latex condom reduces the risk for transmission of HIV and other STDs. Use of female condoms can provide protection from transmission of STDs, although data are limited.

Return to your place in the textBOX K1. Categories for classifying hormonal contraceptives and intrauterine devices

1 = A condition for which there is no restriction for the use of the contraceptive method.

2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

Return to your place in the textTABLE K1. Summary of classifications for hormonal contraceptive methods and intrauterine devices
Condition Cu-IUD LNG-IUD Implants DMPA POP CHCs
Personal Characteristics And Reproductive History
Pregnancy 4* 4* NA* NA* NA* NA*
Age Menarche to
<20 years: 2
Menarche to
<20 years: 2
Menarche to
<18 years: 1
Menarche to
<18 years: 2
Menarche to
<18 years: 1
Menarche to
<40 years: 1
=20 years: 1 =20 years: 1 18–45 years: 1 18–45 years: 1 18–45 years: 1 =40 years: 2
>45 years: 1 >45 years: 2 >45 years: 1
Parity
a. Nulliparous 2 2 1 1 1 1
b. Parous 1 1 1 1 1 1
Breastfeeding
a. <21 days postpartum 2* 2* 2* 4*
b. 21 to <30 days postpartum
  i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 2* 2* 2* 3*
    ii. Without other risk factors for VTE 2* 2* 2* 3*
c. 30–42 days postpartum
  i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 1* 1* 1* 3*
    ii. Without other risk factors for VTE 1* 1* 1* 2*
d. >42 days postpartum 1* 1* 1* 2*
Postpartum (nonbreastfeeding women)
a. <21 days postpartum 1 1 1 4
b. 21–42 days postpartum
  i. With other risk factors for VTE (e.g., age =35 years, previous VTE, thrombophilia, immobility, transfusion at delivery, peripartum cardiomyopathy, BMI =30 kg/m2, postpartum hemorrhage, postcesarean delivery, preeclampsia, or smoking) 1 1 1 3*
  ii. Without other risk factors for VTE 1 1 1 2
c. >42 days postpartum 1 1 1 1
Postpartum (including cesarean delivery)
a. <10 minutes after delivery of the placenta
    i. Breastfeeding 1* 2*
    ii. Nonbreastfeeding 1* 1*
b. 10 minutes after delivery of the placenta to <4 weeks (breastfeeding or nonbreastfeeding) 2* 2*
c. =4 weeks (breastfeeding or nonbreastfeeding) 1* 1*
d. Postpartum sepsis 4 4
Postabortion
a. First trimester 1* 1* 1* 1* 1* 1*
b. Second trimester 2* 2* 1* 1* 1* 1*
c. Immediate postseptic abortion 4 4 1* 1* 1* 1*
Past ectopic pregnancy 1 1 1 1 2 1
History of pelvic surgery (see Postpartum [Including Cesarean Delivery] section) 1 1 1 1 1 1
Smoking
a. Age <35 years 1 1 1 1 1 2
b. Age =35 years
   i. <15 cigarettes per day 1 1 1 1 1 3
   ii. =15 cigarettes per day 1 1 1 1 1 4
Obesity
a. BMI =30 kg/m2 1 1 1 1 1 2
b. Menarche to <18 years and BMI =30 kg/m2 1 1 1 2 1 2
History of bariatric surgery
This condition is associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, or laparoscopic sleeve gastrectomy) 1 1 1 1 1 1
b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass or biliopancreatic diversion) 1 1 1 1 3 COCs: 3
Patch and ring: 1
Cardiovascular Disease
Multiple risk factors for atherosclerotic cardiovascular disease (e.g., older age, smoking, diabetes, hypertension, low HDL, high LDL, or high triglyceride levels) 1 2 2* 3* 2* 3/4*
Hypertension
Systolic blood pressure =160 mm Hg or diastolic blood pressure =100 mm Hg are associated with increased risk for adverse health events as a result of pregnancy (Box 2).
a. Adequately controlled hypertension 1* 1* 1* 2* 1* 3*
b. Elevated blood pressure levels
(properly taken measurements)
   i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg 1* 1* 1* 2* 1* 3*
   ii. Systolic =160 mm Hg or diastolic =100 mm Hg 1* 2* 2* 3* 2* 4*
c. Vascular disease 1* 2* 2* 3* 2* 4*
History of high blood pressure during pregnancy (when current blood pressure is measurable and normal) 1 1 1 1 1 2
Deep venous thrombosis/
Pulmonary embolism
a. History of DVT/PE, not receiving anticoagulant therapy
  i. Higher risk for recurrent DVT/PE (one or more risk factors) 1 2 2 2 2 4
      • History of estrogen-associated DVT/PE
• Pregnancy-associated DVT/PE
• Idiopathic DVT/PE
• Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
  ii. Lower risk for recurrent DVT/PE (no risk factors) 1 2 2 2 2 3
b. Acute DVT/PE 2 2 2 2 2 4
c. DVT/PE and established anticoagulant therapy for at least 3 months
  i. Higher risk for recurrent DVT/PE (one or more risk factors) 2 2 2 2 2 4*
      • Known thrombophilia, including antiphospholipid syndrome
• Active cancer (metastatic, receiving therapy, or within 6 months after clinical remission), excluding nonmelanoma skin cancer
• History of recurrent DVT/PE
    ii. Lower risk for recurrent DVT/PE (no risk factors) 2 2 2 2 2 3*
d. Family history (first-degree relatives) 1 1 1 1 1 2
e. Major surgery
   i. With prolonged immobilization 1 2 2 2 2 4
   ii. Without prolonged immobilization 1 1