Recent Evidence on Depo-Provera (DMPA) Contraceptive Injection
Critical Safety Considerations
Depo-Provera should not be used in patients with current breast cancer, history of blood clots with ongoing risk factors, or history of stroke, as these represent absolute or strong contraindications. 1, 2
Absolute Contraindications
- Current breast cancer (Category 4 - unacceptable health risk) 1
- Past breast cancer with no evidence of disease for less than 5 years (Category 3 - risks usually outweigh benefits) 1
- Unexplained vaginal bleeding before evaluation (Category 3) 1
Strong Precautions for Cardiovascular History
- History of stroke or vascular disease (Category 3 - risks usually outweigh benefits) 1
- Multiple risk factors for arterial cardiovascular disease (Category 3) 1
- Severe uncontrolled hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg) (Category 3) 1
- History of DVT/PE with risk factors for recurrence can be used with caution (Category 2 - benefits generally outweigh risks) 1
Progestin-Only Methods Are Safer for Stroke Risk
For women with stroke history or risk factors, progestin-only contraception like DMPA is reasonable to prevent the increased stroke risk associated with estrogen-containing contraception. 3 Unlike combined hormonal contraceptives that increase stroke risk in a dose-dependent manner with estrogen content, DMPA contains no estrogen and does not carry the same thrombotic risks. 3, 2
Bone Mineral Density Concerns
FDA Black Box Warning vs. Current Guidelines
The FDA black box warning recommends limiting DMPA use to 2 years due to bone mineral density loss, but the American College of Obstetricians and Gynecologists explicitly rejects this restriction, stating that benefits of preventing unwanted pregnancy generally outweigh the risks. 4, 2
Bone Loss Patterns
- BMD decreases 5-6% at spine and hip over 5 years of use, with most loss occurring in the first 2 years 2
- Mean lumbar spine BMD decreases: -2.86% at 1 year, -4.11% at 2 years, -5.38% at 5 years 2
- Bone loss is at least partially reversible after discontinuation, with substantial recovery during the 2-year post-use period 2
- Longer duration of treatment is associated with less complete recovery during the 2-year post-discontinuation period 2
Adolescent-Specific Concerns
In adolescents (ages 12-18), DMPA use is associated with significant BMD decline during a critical period of bone accretion, though preliminary data show partial recovery after discontinuation. 2 The concern is that DMPA may reduce peak bone mass and increase osteoporotic fracture risk in later life, though this remains unknown. 2
Practical Management
- No routine bone density monitoring is recommended, even after 2 years of use 4
- BMD assessment may be considered if the patient has used DMPA for more than 2 years AND has additional osteoporosis risk factors (heavy alcohol use, smoking, chronic corticosteroid use, metabolic bone disease, anorexia nervosa, strong family history of osteoporosis) 1, 4, 2
- All patients should receive counseling on skeletal health: daily calcium intake of 1,300 mg, vitamin D intake of 600 IU, regular weight-bearing exercise, smoking cessation, and alcohol avoidance 3, 5, 4, 2
Efficacy and Administration
Contraceptive Effectiveness
DMPA is highly effective with a typical use failure rate of approximately 6% in the first year and less than 1% with perfect use. 5, 6, 7
Dosing Options
- 150 mg intramuscularly every 13 weeks (91 days) 5, 6
- 104 mg subcutaneously every 13 weeks (equivalent effectiveness and side effects to IM formulation) 5
- Many providers schedule injections every 11-12 weeks to allow buffer time for missed appointments 5
Timing Flexibility
- "Quick start" or "mid-cycle" initiation is acceptable if the provider is reasonably certain the patient is not pregnant 5
- Backup contraception (condoms or abstinence) should be used for the first 7 days after initial injection 5
- Injections can be given up to 2 weeks late (14 weeks from last injection) without requiring additional contraceptive protection 5, 4
- If more than 2 weeks late, the injection can still be given if reasonably certain the patient is not pregnant, but backup contraception is needed for 7 days 5, 4
Common Side Effects
Menstrual Changes
Nearly all patients experience menstrual irregularities initially with unpredictable spotting and bleeding, but bleeding patterns typically improve over time with amenorrhea becoming common. 5, 2 By month 12, amenorrhea was reported by 55% of women, and by month 24,68% of women experienced amenorrhea. 2
Pre-injection counseling about menstrual changes reduces discontinuation rates, making this counseling essential before initiation. 5
Weight Gain
Weight gain occurs in some but not all patients, with weight gain at 6 months (>5% increase) being a significant predictor of future excessive weight gain. 5, 4 This early weight gain pattern should prompt discussion about continuing the method. 4
Return to Fertility
Return to fertility is delayed after discontinuation, typically 9-18 months, which may be a consideration for women planning pregnancy in the near future. 1, 4 The majority of women ovulate within 15-49 weeks after the last injection. 5
Cancer Risk Profile
Breast Cancer
Long-term surveillance found slight or no increased overall risk of breast cancer with DMPA use. 2 However, women whose first exposure was within the previous 4 years and who were under 35 years of age showed an increased relative risk of 2.19 (95% CI 1.23-3.89). 2 The overall relative risk for ever-users was only 1.2 (95% CI 0.96-1.52). 2
Other Cancers
- No overall increased risk of ovarian, liver, or cervical cancer 2
- Prolonged protective effect reducing the risk of endometrial cancer 2, 6
Advantages Over Combined Hormonal Contraceptives
DMPA has no appreciable effects on blood pressure or thrombosis risk, providing a simple, effective alternative for women who cannot use combined oral contraceptives for these reasons. 7 This makes it particularly suitable for:
- Women with hypertension (if not severe/uncontrolled) 3
- Women with migraine without aura 3
- Women who cannot tolerate estrogen 3
- Women with history of thromboembolism (with careful risk assessment) 1
Special Populations
Adolescents
DMPA is generally safe for use in adolescents, but bone health considerations are particularly important during this critical period of bone accretion. 3, 1, 2 The American Academy of Pediatrics recommends counseling adolescents about calcium intake (1,300 mg daily), vitamin D (600 IU daily), and weight-bearing exercise. 3, 1
Cancer Survivors
For women with history of breast cancer, DMPA should be used with extreme caution or avoided, as past breast cancer with no evidence of disease for less than 5 years is Category 3 (risks usually outweigh benefits). 3, 1 For other cancer survivors who have been free of cancer for at least 6 months and have no history of hormonally mediated cancers, DMPA may be appropriate. 3
HIV-Infected Patients
HIV-infected women should be informed that DMPA may or may not increase HIV transmission risk to partners and should be counseled to continue condom use for HIV prevention. 5 DMPA has no significant interactions with antiretroviral agents including efavirenz, zidovudine, lamivudine, nevirapine, and nelfinavir. 5
Monitoring Requirements
No examinations or laboratory tests are needed before initiating DMPA, and no routine blood work is recommended during ongoing use. 4 Baseline weight and BMI measurement may be useful for monitoring over time. 4
Key Clinical Pitfalls to Avoid
- Do not discontinue DMPA at 2 years based solely on duration concerns, as this increases risk of unintended pregnancy without clear benefit 4
- Do not routinely order bone density scans after 2 years of use unless other osteoporosis risk factors are present 4
- Do not fail to counsel about menstrual irregularities before first injection, as this significantly reduces discontinuation 5
- Do not assume amenorrhea after DMPA is pathologic without ruling out other causes 5