What is the Depo‑Provera (medroxyprogesterone acetate) injectable contraceptive, its dosing schedule, contraindications, common side effects, and alternative long‑acting reversible contraceptive options?

Depo-Provera (Medroxyprogesterone Acetate) Injectable Contraceptive

Depo-Provera is a highly effective progestin-only injectable contraceptive administered every 13 weeks (3 months) as either 150 mg intramuscularly or 104 mg subcutaneously, with a typical-use failure rate of 0.3-6% and perfect-use failure rate of 0.2%. 1, 2

Dosing Schedule and Administration

Standard Dosing

• Two equivalent formulations exist: 150 mg intramuscular (IM) injection every 13 weeks OR 104 mg subcutaneous (SC) injection every 13 weeks 2, 3
• Timing flexibility: Injections can be given up to 2 weeks late (15 weeks from last injection) without requiring backup contraception 3, 2
• Initial injection: Requires backup contraception for the first 7 days 1
• Late injections (>15 weeks): Administer only if reasonably certain patient is not pregnant; require abstinence or backup contraception for 7 days 2

Self-Administration Option

• The CDC recommends offering self-administered subcutaneous DMPA-SC as an additional approach to improve contraceptive access and reproductive autonomy 3
• This is considered off-label use, as FDA labeling specifies healthcare professional administration 3
• Requires instruction on injection technique, sharps disposal, and access to follow-up care 3

Contraindications

Absolute contraindications include: 2, 4

• Undiagnosed vaginal bleeding
• Known or suspected breast malignancy
• History of stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis
• Active thromboembolic disorders
• Cerebral vascular disease
• Liver dysfunction or disease
• History of meningiomas
• Known pregnancy

Common Side Effects

Menstrual Irregularities (Most Common)

• Nearly all patients experience menstrual changes initially, including irregular bleeding, spotting, or heavy bleeding 1, 5
• Amenorrhea becomes increasingly common with continued use (57% by end of first year) 4, 6
• Management: Reassure patients these changes are expected and not harmful; offer NSAIDs for 5-7 days if bleeding is persistent and bothersome 5
• Pre-injection counseling about menstrual changes significantly improves continuation rates 1

Weight Gain

• Common concern with significant individual variability 1, 5
• 21% of adolescents experience early weight gain, and those gaining >5% at 6 months are strong predictors of continued excessive weight gain 1, 5

Bone Mineral Density Loss

• The American College of Obstetricians and Gynecologists does NOT recommend limiting use to 2 years, as benefits of pregnancy prevention outweigh bone density risks 1, 5
• BMD substantially recovers after discontinuation 5
• All patients must receive counseling on: daily calcium intake (≈1300 mg), vitamin D supplementation (600 IU), regular weight-bearing exercise, and smoking cessation 1, 2, 5
• Evaluate bone density only when long-term use is needed and other methods are inadequate 1

Other Side Effects

• Headache, breast pain (mastalgia), hair loss, changes in libido 5
• Nervousness, abdominal pain or discomfort, dizziness, asthenia 4

Delayed Return to Fertility

• Typical delay of 9-18 months after discontinuation while endometrial lining and ovulatory function return 5
• Does not permanently affect fertility 6

Clinical Benefits Beyond Contraception

Depo-Provera offers multiple non-contraceptive benefits: 1

• Improves dysmenorrhea and protects against iron-deficiency anemia through reduced menstrual bleeding
• Reduces risk of endometrial cancer with prolonged use
• May raise seizure threshold in epileptic patients
• May decrease sickle cell crises
• Reduces incidence of pelvic inflammatory disease 6

Special Populations

Estrogen Contraindications

• Ideal for women who cannot use estrogen-containing contraceptives, including those with: 1, 3
  • History of thromboembolism
  • Migraine with aura
  • Cardiovascular disease
  • Antiphospholipid antibody positivity
  • Systemic lupus erythematosus with moderate-to-severe disease activity

Breastfeeding Women

• CDC Medical Eligibility Criteria rates DMPA as Category 1 (no restriction) for women ≥1 month postpartum who are breastfeeding 1

HIV-Positive Women

• HIV infection is NOT a contraindication to Depo-Provera use 2
• DMPA levels are not reduced by antiretroviral agents and largely free of antiretroviral interactions 2

Women on Rifampin

• CDC recommends DMPA for women on long-term rifampin therapy, as effectiveness is not reduced (unlike combined oral contraceptives) 1

Alternative Long-Acting Reversible Contraceptive (LARC) Options

The American College of Rheumatology conditionally recommends IUDs or subdermal implants as first-line contraceptives due to <1% failure rates, but Depo-Provera remains an excellent alternative when: 1

• IUD insertion is declined or contraindicated
• Implant placement is not feasible
• Patient preference favors an injectable method
• Therapeutic menstrual suppression is desired

LARC Comparison

• Copper or progestin IUDs: <1% annual pregnancy rate, no hormonal side effects with copper IUD, lasts 3-12 years depending on type 3
• Subdermal progestin implant (Nexplanon): <1% annual pregnancy rate, lasts 3 years 3
• Combined estrogen-progestin methods: 3-8% annual pregnancy rate with typical use 3

Follow-Up Recommendations

No routine follow-up visits are required between scheduled injections 3, 2

Patients should contact healthcare provider to: 3

• Discuss side effects or problems
• Change contraceptive methods
• Address questions or concerns about reinjection

At reinjection visits, assess: 2

• Patient satisfaction with method
• New medical conditions or medications that would change DMPA appropriateness
• Weight changes (counsel if concerning)
• Screen for new contraindications

Common Pitfalls to Avoid

• Do NOT limit use to 2 years based solely on bone density concerns 2, 5
• Do NOT require routine follow-up visits between injections 2
• Do NOT forget to counsel about STI protection: DMPA provides no protection against sexually transmitted infections; recommend condoms 2
• Do NOT overlook unscheduled bleeding as potential STI indicator: Offer appropriate STI testing in adolescents with irregular bleeding 5
• Do NOT fail to provide pre-injection counseling about menstrual changes: This significantly improves continuation rates 1