Injectables

Timing

• The first DMPA injection can be given at any time if it is reasonably certain that the woman is not pregnant (Box 2).

Need for Back-Up Contraception

• If DMPA is started within the first 7 days since menstrual bleeding started, no additional contraceptive protection is needed.
• If DMPA is started >7 days since menstrual bleeding started, the woman needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days.

Special Considerations

Amenorrhea (Not Postpartum)

• Timing: The first DMPA injection can be given at any time if it is reasonably certain that the woman is not pregnant (Box 2).
• Need for back-up contraception: The woman needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days.

Postpartum (Breastfeeding)

• Timing: The first DMPA injection can be given at any time, including immediately postpartum (U.S. MEC 2 if <1 month postpartum and U.S. MEC 1 if ≥1 month postpartum) if it is reasonably certain that the woman is not pregnant (Box 2).
• Need for back-up contraception: If the woman is <6 months postpartum, amenorrheic, and fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority [≥85%] of feeds are breastfeeds) (27), no additional contraceptive protection is needed. Otherwise, a woman who is ≥21 days postpartum and has not experienced return of her menstrual cycle needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days. If her menstrual cycles have returned and it has been >7 days since menstrual bleeding started, she needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days.

Postpartum (Not Breastfeeding)

• Timing: The first DMPA injection can be given at any time, including immediately postpartum (U.S. MEC 1) if it is reasonably certain that the woman is not pregnant (Box 2).
• Need for back-up contraception: : If a woman is <21 days postpartum, no additional contraceptive protection is needed. A woman who is ≥21 days postpartum and has not experienced return of her menstrual cycle needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days. If her menstrual cycles have returned and it has been >7 days since menstrual bleeding started, she needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days.

Postabortion (Spontaneous or Induced)

• Timing: The first DMPA injection can be given within the first 7 days, including immediately after the abortion (U.S. MEC 1).
• Need for back-up contraception: The woman needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days unless the injection is given at the time of a surgical abortion.

Switching from Another Contraceptive Method

• Timing: The first DMPA injection can be given immediately if it is reasonably certain that the woman is not pregnant (Box 2). Waiting for her next menstrual period is unnecessary.
• Need for back-up contraception: If it has been >7 days since menstrual bleeding started, the woman needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days.
• Switching from an IUD: If the woman has had sexual intercourse since the start of her current menstrual cycle and it has been >5 days since menstrual bleeding started, theoretically, residual sperm might be in the genital tract, which could lead to fertilization if ovulation occurs. A health-care provider may consider any of the following options:
  • Advise the women to retain the IUD for at least 7 days after the injection and return for IUD removal.
  • Advise the woman to abstain from sexual intercourse or use barrier contraception for 7 days before removing the IUD and switching to the new method.
  • If the woman cannot return for IUD removal and has not abstained from sexual intercourse or used barrier contraception for 7 days, advise the woman to use ECPs (with the exception of UPA) at the time of IUD removal.

Comments and Evidence Summary. In situations in which the health-care provider is uncertain whether the woman might be pregnant, the benefits of starting DMPA likely exceed any risk; therefore, starting DMPA should be considered at any time, with a follow-up pregnancy test in 2–4 weeks. If a woman needs to use additional contraceptive protection when switching to DMPA from another contraceptive method, consider continuing her previous method for 7 days after DMPA injection.

A systematic review identified eight articles examining DMPA initiation on different days of the menstrual cycle (161). Evidence from two studies with small sample sizes indicated that DMPA injections given up to day 7 of the menstrual cycle inhibited ovulation; when DMPA was administered after day 7, ovulation occurred in some women. Cervical mucus was of poor quality (i.e., not favorable for sperm penetration) in 90% of women within 24 hours of the injection (Level of evidence: II-2, fair) (162–164). Studies found that use of another contraceptive method until DMPA could be initiated (bridging option) did not help women initiate DMPA and was associated with more unintended pregnancies than immediate receipt of DMPA (165–169) (Level of evidence: I to II-3, fair to poor, indirect).

Self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) should be made available as an additional approach to deliver injectable contraception.

Comments and Evidence Summary: Self-administered DMPA-SC is a user-controlled method that has the potential to improve contraceptive access and increase reproductive autonomy. Self-administered DMPA-SC should be made available as an additional approach; provider administered DMPA should remain available. Self-administered DMPA-SC should be offered in the context of shared decision-making, with a focus on patient preferences and access to the full range of contraceptive methods. Existing recommendations in the “U.S. Medical Eligibility Criteria for Contraceptive Use” and “U.S. Selected Practice Recommendations for Contraceptive Use” for provider-administered DMPA also apply to self-administered DMPA-SC. As with provider-administered DMPA, no routine follow-up is required; however, the patient should be encouraged to contact a healthcare provider at any time to discuss side effects or other problems, if there is a desire to change the method being used (including requesting provider-administered DMPA), or if there are questions or concerns around re-injection.

A systematic review and meta-analysis of three randomized controlled trials (RCTs) and three prospective cohort studies compared self-administration of DMPA-SC with provider-administered DMPA-SC or DMPA-IM (354). Higher rates of continuation were observed with self-administration compared with provider-administration (pooled relative risk [RR] 1.27, 95% confidence interval [CI] 1.16-1.39 for three RCTs and pooled RR 1.18, 95% CI 1.10-1.26 for three cohort studies). Pregnancy rates were low and did not differ between self-administered and provider-administered groups (four studies). Two studies found higher rates of injection site reactions with self-administered DMPA-SC compared with provider-administered DMPA-IM, and two studies found no differences. No other side effects or adverse events were increased with self-administered DMPA-SC.

Among healthy women, no examinations or tests are needed before initiation of DMPA, although a baseline weight and BMI measurement might be useful for monitoring DMPA users over time (Table 3). Women with known medical problems or other special conditions might need additional examinations or tests before being determined to be appropriate candidates for a particular method of contraception. U.S. MEC might be useful in such circumstances (5).

Comments and Evidence Summary. Weight (BMI): Obese women can use (U.S. MEC 1) or generally can use (U.S. MEC 2) DMPA (5); therefore, screening for obesity is not necessary for the safe initiation of DMPA. However, measuring weight and calculating BMI at baseline might be helpful for monitoring any changes and counseling women who might be concerned about weight change perceived to be associated with their contraceptive method. (See guidance on follow-up for DMPA users for evidence on weight gain with DMPA use.)

Bimanual examination and cervical inspection: Pelvic examination is not necessary before initiation of DMPA because it does not facilitate detection of conditions for which DMPA would be unsafe. Although women with current breast cancer should not use DMPA (U.S. MEC 4), and women with severe hypertension, heart disease, vascular disease, or certain liver diseases generally should not use DMPA (U.S. MEC 3) (5), none of these conditions are likely to be detected by pelvic examination (145). A systematic review identified two case-control studies that compared delayed versus immediate pelvic examination before initiation of hormonal contraceptives, specifically oral contraceptives or DMPA (95). No differences in risk factors for cervical neoplasia, incidence of STDs, incidence of abnormal Papanicolaou smears, or incidence of abnormal wet mounts were observed (Level of evidence: II-2, fair, direct).

Blood pressure: Women with hypertension generally can use DMPA (U.S. MEC 2), with the exception of women with severe hypertension or vascular disease, who generally should not use DMPA (U.S. MEC 3) (5). Screening for hypertension before initiation of DMPA is not necessary because of the low prevalence of undiagnosed severe hypertension and the high likelihood that women with these conditions already would have had them diagnosed. A systematic review did not identify any evidence regarding outcomes among women who were screened versus not screened with a blood pressure measurement before initiation of progestin-only contraceptives (170). The prevalence of undiagnosed hypertension among women of reproductive age is low. During 2009–2012 among women aged 20–44 years in the United States, the prevalence of hypertension was 8.7% (84). During 1999–2008, the percentage of women aged 20–44 years with undiagnosed hypertension was 1.9% (85).

Glucose: Although women with complicated diabetes generally should not use DMPA (U.S. MEC 3) (5), screening for diabetes before initiation of DMPA is not necessary because of the low prevalence of undiagnosed diabetes and the high likelihood that women with complicated diabetes would already have had the condition diagnosed. A systematic review did not identify any evidence regarding outcomes among women who were screened versus not screened with glucose measurement before initiation of hormonal contraceptives (57). The prevalence of diabetes among women of reproductive age is low.During 2009–2012 among women aged 20–44 years in the United States, the prevalence of diabetes was 3.3% (84). During 1999–2008, the percentage of women aged 20–44 years with undiagnosed diabetes was 0.5% (85). Although hormonal contraceptives can have some adverse effects on glucose metabolism in healthy and diabetic women, the overall clinical effect is minimal (171–177).

Lipids: Screening for dyslipidemias is not necessary for the safe initiation of injectables because of the low prevalence of undiagnosed disease in women of reproductive age and the low likelihood of clinically significant changes with use of hormonal contraceptives. A systematic review did not identify any evidence regarding outcomes among women who were screened versus not screened with lipid measurement before initiation of hormonal contraceptives (57). During 2009–2012 among women aged 20–44 years in the United States, 7.6% had high cholesterol, defined as total serum cholesterol ≥240 mg/dL (84). During 1999–2008, the prevalence of undiagnosed hypercholesterolemia among women aged 20–44 years was approximately 2% (85). Studies have shown mixed results about the effects of hormonal methods on lipid levels among both healthy women and women with baseline lipid abnormalities, and the clinical significance of these changes is unclear (86–89).

Liver enzymes: Although women with certain liver diseases generally should not use DMPA (U.S. MEC 3) (5), screening for liver disease before initiation of DMPA is not necessary because of the low prevalence of these conditions and the high likelihood that women with liver disease already would have had the condition diagnosed. A systematic review did not identify any evidence regarding outcomes among women who were screened versus not screened with liver enzyme tests before initiation of hormonal contraceptives (57). In 2012, among U.S. women, the percentage with liver disease (not further specified) was 1.3% (90). In 2013, the incidence of acute hepatitis A, B, or C was ≤1 per 100,000 U.S. population (91). During 2002–2011, the incidence of liver carcinoma among U.S. women was approximately 3.7 per 100,000 population (92). Because estrogen and progestins are metabolized in the liver, the use of hormonal contraceptives among women with liver disease might, theoretically, be a concern. The use of hormonal contraceptives, specifically COCs and POPs, does not affect disease progression or severity in women with hepatitis, cirrhosis, or benign focal nodular hyperplasia (93,94), although evidence is limited and no evidence exists for DMPA.

Clinical breast examination: Although women with current breast cancer should not use DMPA (U.S. MEC 4) (5), screening asymptomatic women with a clinical breast examination before initiating DMPA is not necessary because of the low prevalence of breast cancer among women of reproductive age. A systematic review did not identify any evidence regarding outcomes among women who were screened versus not screened with a clinical breast examination before initiation of hormonal contraceptives (95). The incidence of breast cancer among women of reproductive age in the United States is low. In 2012, the incidence of breast cancer among women aged 20–49 years was approximately 70.7 per 100,000 women (96).

Other screening: Women with anemia, thrombogenic mutations, cervical intraepithelial neoplasia, cervical cancer, HIV infection, or other STDs can use (U.S. MEC 1) or generally can use (U.S. MEC 2) DMPA (5); therefore, screening for these conditions is not necessary for the safe initiation of DMPA.

These recommendations address when routine follow-up is recommended for safe and effective continued use of contraception for healthy women. The recommendations refer to general situations and might vary for different users and different situations. Specific populations that might benefit from more frequent follow-up visits include adolescents, those with certain medical conditions or characteristics, and those with multiple medical conditions.

• Advise the woman to return at any time to discuss side effects or other problems, if she wants to change the method being used, and when it is time for reinjection. No routine follow-up visit is required.
• At other routine visits, health-care providers seeing injectable users should do the following:
  • Assess the woman’s satisfaction with her contraceptive method and whether she has any concerns about method use.
  • Assess any changes in health status, including medications, that would change the appropriateness of the injectable for safe and effective continued use based on U.S. MEC (e.g., category 3 and 4 conditions and characteristics).
  • Consider assessing weight changes and counseling women who are concerned about weight change perceived to be associated with their contraceptive method.

Comments and Evidence Summary. Although no evidence exists regarding whether a routine follow-up visit after initiating DMPA improves correct or continued use, monitoring weight or BMI change over time is important for DMPA users.

A systematic review identified a limited body of evidence that examined whether weight gain in the few months after DMPA initiation predicted future weight gain (123). Two studies found significant differences in weight gain or BMI at follow-up periods ranging from 12 to 36 months between early weight gainers (i.e., those who gained >5% of their baseline body weight within 6 months after initiation) and those who were not early weight gainers (178,179). The differences between groups were more pronounced at 18, 24, and 36 months than at 12 months. One study found that most adolescent DMPA users who had gained >5% of their baseline weight by 3 months gained even more weight by 12 months (180) (Level of evidence: II-2, fair, to II-3, fair, direct).

Reinjection Interval

• Provide repeat DMPA injections every 3 months (13 weeks).

Special Considerations

Early Injection

• The repeat DMPA injection can be given early when necessary.

Late Injection

• The repeat DMPA injection can be given up to 2 weeks late (15 weeks from the last injection) without requiring additional contraceptive protection.
• If the woman is >2 weeks late (>15 weeks from the last injection) for a repeat DMPA injection, she can have the injection if it is reasonably certain that she is not pregnant (Box 2). She needs to abstain from sexual intercourse or use additional contraceptive protection for the next 7 days. She might consider the use of emergency contraception (with the exception of UPA) if appropriate.

Comments and Evidence Summary. No time limits exist for early injections; injections can be given when necessary (e.g., when a woman cannot return at the routine interval). WHO has extended the time that a woman can have a late reinjection (i.e., grace period) for DMPA use from 2 weeks to 4 weeks on the basis of data from one study showing low pregnancy rates through 4 weeks; however, the CDC expert group did not consider the data to be generalizable to the United States because a large proportion of women in the study were breastfeeding. Therefore, U.S. SPR recommends a grace period of 2 weeks.

A systematic review identified 12 studies evaluating time to pregnancy or ovulation after the last injection of DMPA (181). Although pregnancy rates were low during the 2-week interval following the reinjection date and for 4 weeks following the reinjection date, data were sparse and one study included a large proportion of breastfeeding women (182–184). Studies also indicated a wide variation in time to ovulation after the last DMPA injection, with the majority ranging from 15 to 49 weeks from the last injection (185–193) (Level of evidence: II-2, fair, direct).

• Before DMPA initiation, provide counseling about potential changes in bleeding patterns during DMPA use. Amenorrhea and unscheduled spotting or light bleeding is common with DMPA use, and heavy or prolonged bleeding can occur with DMPA use. These bleeding irregularities are generally not harmful and might decrease with continued DMPA use.

Unscheduled Spotting or Light Bleeding

• If clinically indicated, consider an underlying gynecological problem, such as interactions with other medications, an STD, pregnancy, or new pathologic uterine conditions (e.g., polyps or fibroids). If an underlying gynecological problem is found, treat the condition or refer for care.
• If an underlying gynecologic problem is not found and the woman wants treatment, the following treatment option during days of bleeding can be considered:
  • NSAIDs for short-term treatment (5–7 days)
• If unscheduled spotting or light bleeding persists and the woman finds it unacceptable, counsel her on alternative contraceptive methods, and offer another method if it is desired.

Heavy or Prolonged Bleeding

• If clinically indicated, consider an underlying gynecological problem, such as interactions with other medications, an STD, pregnancy, or new pathologic uterine conditions (such as fibroids or polyps). If an underlying gynecologic problem is identified, treat the condition or refer for care.
• If an underlying gynecologic problem is not found and the woman wants treatment, the following treatment options during days of bleeding can be considered:
  • NSAIDS for short-term treatment (5–7 days)
  • Hormonal treatment (if medically eligible) with low-dose COCs or estrogen for short-term treatment (10–20 days)
• If heavy or prolonged bleeding persists and the woman finds it unacceptable, counsel her on alternative contraceptive methods, and offer another method if it is desired.

Amenorrhea

• Amenorrhea does not require any medical treatment. Provide reassurance.
  • If a woman’s regular bleeding pattern changes abruptly to amenorrhea, consider ruling out pregnancy if clinically indicated.
• If amenorrhea persists and the woman finds it unacceptable, counsel her on alternative contraceptive methods, and offer another method if it is desired.

Comments and Evidence Summary. During contraceptive counseling and before initiation of DMPA, information about common side effects such as irregular bleeding should be discussed. Unscheduled bleeding or spotting is common with DMPA use (194). Additionally, amenorrhea is common after ≥1 years of continuous use (194,195). These bleeding irregularities are generally not harmful. Enhanced counseling among DMPA users detailing expected bleeding patterns and reassurance that these irregularities generally are not harmful has been shown to reduce DMPA discontinuation in clinical trials (124,125).

A systematic review, as well as two additional studies, examined the treatment of bleeding irregularities during DMPA use (195–197). Two small studies found significant cessation of bleeding within 7 days of starting treatment among women taking valdecoxib for 5 days or mefenamic acid for 5 days compared with placebo (198,199). Treatment with ethinyl estradiol was found to stop bleeding better than placebo during the treatment period, although rates of discontinuation were high, and safety outcomes were not examined (200). In one small study among DMPA users who had been experiencing amenorrhea for 2 months, treatment with COCs was found to alleviate amenorrhea better than placebo (201). No studies examined the effects of aspirin on bleeding irregularities among DMPA users.