Injectables

Overview

Progestin-only injectable contraceptives (DMPA, 150 mg intramuscularly [DMPA-IM] or 104 mg subcutaneously [DMPA-SC]) are available in the United States; the only difference between these two formulations is the route of administration. Approximately four out of 100 DMPA users will become pregnant in the first year with typical use.^[28] DMPA is reversible and can be used by patients of all ages, including adolescents. DMPA does not protect against STIs, including HIV infection, and patients using DMPA should be counseled that consistent and correct use of external (male) latex condoms reduces the risk for STIs, including HIV infection.^[31] Use of internal (female) condoms can provide protection from STIs, including HIV infection, although data are limited.^[31] Patients also should be counseled that PrEP, when taken as prescribed, is highly effective for preventing HIV infection.^[32]

Initiation of injectables

Timing

• The first DMPA injection may be administered at any time if it is reasonably certain that the patient is not pregnant (Box 3).

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 patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.

Special Considerations

Amenorrhea (Not Postpartum)

• Timing: The first DMPA injection may be administered at any time if it is reasonably certain that the patient is not pregnant (Box 3).
• Need for back-up contraception: The patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.

Postpartum (Breastfeeding)

• Timing: The first DMPA injection may be administered at any time, including immediately postpartum (U.S. MEC 2 if <30 days postpartum; U.S. MEC 2 if 30–42 days postpartum with other risk factors for venous thromboembolism; U.S. MEC 1 if 30–42 days postpartum without other risk factors for venous thromboembolism; U.S. MEC 1 if >42 days postpartum), if it is reasonably certain that the patient is not pregnant (Box 3).^[1]
• Need for back-up contraception: If the patient is <6 months postpartum, amenorrheic, and fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority [≥85%] of feeds are breastfeeds),^[44] no additional contraceptive protection is needed. Otherwise, a patient who is ≥21 days postpartum and whose menstrual cycle has not returned needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days. If the patient's menstrual cycle has returned and it has been >7 days since menstrual bleeding started, the patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.

Postpartum (Nonbreastfeeding)

• Timing: The first DMPA injection may be administered at any time, including immediately postpartum (U.S. MEC 2 if <21 days postpartum; U.S. MEC 2 if 21–42 days postpartum with other risk factors for venous thromboembolism; U.S. MEC 1 if 21–42 days postpartum without other risk factors for venous thromboembolism; U.S. MEC 1 if >42 days postpartum),^[1] if it is reasonably certain that the patient is not pregnant (Box 3).
• Need for back-up contraception: If the patient is <21 days postpartum, no additional contraceptive protection is needed. A patient who is ≥21 days postpartum and whose menstrual cycle has not returned needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days. If the patient's menstrual cycle has returned and it has been >7 days since menstrual bleeding started, the patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.

Postabortion (Spontaneous or Induced)

• Timing: The first DMPA injection may be administered at any time postabortion, including immediately after abortion completion, if it is reasonably certain that the patient is not pregnant (Box 3), or at the time of medication abortion initiation (U.S. MEC 1 or 2).^[1]
• After a first trimester medication abortion that included mifepristone, concurrent administration of DMPA with mifepristone might slightly decrease medication abortion effectiveness and increase risk for ongoing pregnancy (U.S. MEC 2).^[1] Risk for ongoing pregnancy with concurrent administration of DMPA with mifepristone versus DMPA administration after abortion completion should be considered along with personal preference and access to follow-up abortion and contraceptive care.
• Need for back-up contraception: The patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days unless the injection is administered at the time of an abortion.

Switching From Another Contraceptive Method

• Timing: The first DMPA injection may be administered immediately if it is reasonably certain that the patient is not pregnant (Box 3). Waiting for the patient's next menstrual cycle is unnecessary.
• Need for back-up contraception: If it has been >7 days since menstrual bleeding started, the patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.
• Switching from an IUD: In addition to the need for back-up contraception when starting DMPA, there might be additional concerns when switching from an IUD. If the patient has had sexual intercourse since the start of their 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 to address the potential for residual sperm:
  • Advise the patient to retain the IUD for at least 7 days after the injection and return for IUD removal.
  • Advise the patient to abstain from sexual intercourse or use barrier methods (e.g., condoms) for 7 days before removing the IUD and switching to the new method. If it has been >5 days since menstrual bleeding started, the patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.
  • If the patient cannot return for IUD removal and has not abstained from sexual intercourse or used barrier methods (e.g., condoms) for 7 days, advise the patient to use ECPs (with the exception of UPA) at the time of IUD removal. If it has been >5 days since menstrual bleeding started, the patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days.

Comments and Evidence Summary

In situations in which the health care provider is uncertain whether the patient 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 patient needs to use additional contraceptive protection when switching to DMPA from another contraceptive method, consider continuing their previous method for 7 days after DMPA injection. (As appropriate, see recommendations for Emergency Contraception.)

A systematic review identified eight articles examining DMPA initiation on different days of the menstrual cycle.^[212] Evidence from two studies with small sample sizes indicated that DMPA injections administered up to day 7 of the menstrual cycle inhibited ovulation; when DMPA was administered after day 7, ovulation occurred in certain women. Cervical mucus was of poor quality (i.e., not favorable for sperm penetration) in 90% of women within 24 hours of the injection^[213-215] (Level of evidence: II-2, fair). 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^[216-220] (Level of evidence: I to II-3, fair to poor, indirect).

Examinations and tests needed before initiation of an injectable

Among healthy patients, no examinations or tests are needed before initiation of DMPA, although a baseline weight and BMI measurement might be useful for addressing any concerns about changes in weight over time (Table 3). Patients 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.^[1]

Self-administration of subcutaneous injectable contraception

• Self-administered 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. Recommendations in the U.S. MEC^[1] and U.S. SPR 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 health care provider at any time 1) to discuss side effects or other problems, 2) if there is a desire to change the method being used (including requesting provider-administered DMPA), or 3) if there are questions or concerns about reinjection.^[14] FDA labeling states that DMPA-SC is only to be administered by a health care professional (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/021583s033s034lbl.pdf). Therefore, self-administration of DMPA-SC is considered "off-label".^[14]

A systematic review and meta-analysis of three RCTs and three prospective cohort studies compared self-administration of DMPA-SC with provider-administered DMPA-SC or DMPA-IM.^[235],[236] Higher rates of continuation were observed with self-administration compared with provider-administration (pooled relative risk [RR] = 1.27; 95% 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 (Certainty of evidence: moderate for RCTs and very low for observational studies for continuation; moderate for RCTs and very low for observational studies for pregnancy rates; low for RCTs and very low for observational studies for side effects).

Routine follow-up after injectable initiation

These recommendations address when routine follow-up is recommended for safe and effective continued use of contraception for healthy patients. The recommendations refer to general situations and might vary for different users and different situations. Specific populations who 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 patient that they may contact their provider at any time to discuss side effects or other problems, if they want 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 patient's satisfaction with their contraceptive method and whether they have 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 on the basis of U.S. MEC (e.g., category 3 and 4 conditions and characteristics).^[1]
  • Consider assessing weight changes and discussing concerns about any changes in weight and whether changes might be related to use of the 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.^[21] 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.^[237],[238] 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^[239] (Level of evidence: II-2, fair, to II-3, fair, direct).

Timing of repeat injections

Reinjection Interval

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

Special Considerations

Early Injection

• The repeat DMPA injection may be administered early when necessary.

Late Injection

• The repeat DMPA injection may be administered up to 2 weeks late (15 weeks from the last injection) without requiring additional contraceptive protection.
• If the patient is >2 weeks late (>15 weeks from the last injection) for a repeat DMPA injection, they may have the injection if it is reasonably certain that they are not pregnant (Box 3). The patient needs to abstain from sexual intercourse or use barrier methods (e.g., condoms) for the next 7 days. The patient may 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 administered when necessary (e.g., when a patient cannot return at the routine interval). WHO has extended the time that a patient 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 demonstrating 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.^[240] Although pregnancy rates were low during the 2-week interval after the reinjection date and for 4 weeks after the reinjection date, data were sparse, and one study included a large proportion of breastfeeding women.^[241-243] 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^[244-252] (Level of evidence: II-2, fair, direct).

Bleeding irregularities (including amenorrhea) during injectable use

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

Spotting or Light Bleeding

• If clinically indicated, consider an underlying health condition, such as interactions with other medications, STIs, pregnancy, thyroid disorders, or new pathologic uterine conditions (e.g., polyps or fibroids). If an underlying health condition is found, treat the condition or refer for care.
• Explore patient goals, including continued DMPA use (with or without treatment for bleeding irregularities) or discontinuation of DMPA. If the patient wants to continue DMPA use, provide reassurance, discuss options for management of bleeding irregularities if desired, and advise the patient that they may contact their provider at any time to discuss bleeding irregularities or other side effects.
• If the patient wants to discontinue DMPA at any time, offer counseling on alternative contraceptive methods and initiate another method if it is desired.
• If the patient wants treatment, the following treatment option during days of bleeding may be considered, depending on the patient's preferences, treatment goals, and medical history:
  • NSAIDs: short-term treatment, 5–7 days

Heavy or Prolonged Bleeding

• If clinically indicated, consider an underlying health condition, such as interactions with other medications, STIs, pregnancy, thyroid disorders, or new pathologic uterine conditions (such as fibroids or polyps). If an underlying health condition is identified, treat the condition or refer for care.
• Explore patient goals, including continued DMPA use (with or without treatment for bleeding irregularities) or discontinuation of DMPA. If the patient wants to continue DMPA use, provide reassurance, discuss options for management of bleeding irregularities if desired, and advise the patient that they may contact their provider at any time to discuss bleeding irregularities or other side effects.
• If the patient wants to discontinue DMPA at any time, offer counseling on alternative contraceptive methods and initiate another method if it is desired.
• If the patient wants treatment, the following treatment options during days of bleeding may be considered, depending on the patient's preferences, treatment goals, and medical history:
  • NSAIDs: short-term treatment, 5–7 days
  • Hormonal treatment: low-dose COCs or estrogen for short-term treatment, 10–20 days

Amenorrhea

• Amenorrhea does not require any medical treatment. Provide reassurance.
  • If a patient's regular bleeding pattern changes abruptly to amenorrhea, consider ruling out pregnancy if clinically indicated.
• If the patient wants to discontinue DMPA, offer counseling on alternative contraceptive methods, and initiate 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. Bleeding or spotting is common with DMPA use.^[253] In addition, amenorrhea is common after ≥1 years of continuous use.^[253],[254] These bleeding irregularities are generally not harmful but might be bothersome to the patient. Enhanced counseling among DMPA users detailing expected bleeding patterns and reassurance that these irregularities generally are not harmful has been demonstrated to reduce DMPA discontinuation in clinical trials.^[147],[148]

Evidence is limited on specific drugs, doses, and durations of use for effective treatments for bleeding irregularities with DMPA use. Therefore, this report includes general recommendations for treatments to consider rather than specific regimens.

A systematic review, as well as two additional studies, examined the treatment of bleeding irregularities during DMPA use.^[254-256] 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.^[257],[258] Treatment with EE was found to stop bleeding better than placebo during the treatment period, although rates of discontinuation were high and safety outcomes were not examined.^[259] 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.^[260] No studies examined the effects of aspirin on bleeding irregularities among DMPA users.