What are the side effects of medroxyprogesterone (Depo-Provera)?

Side Effects of Medroxyprogesterone Acetate (Depo-Provera)

Most Common and Clinically Significant Side Effects

Medroxyprogesterone acetate causes menstrual irregularities, weight gain, and bone mineral density loss as its most significant side effects, with nearly all patients experiencing menstrual changes initially. 1, 2

Menstrual Changes

• Nearly all patients experience menstrual irregularities initially, including breakthrough bleeding, spotting, irregular bleeding, or amenorrhea 2, 3
• These changes typically improve over time but are the most common reason for discontinuation 4
• Abnormal uterine bleeding patterns (irregular, increased, or decreased flow) occur frequently 3
• Counseling before initiation about expected menstrual changes significantly improves continuation rates 1, 2

Weight Gain

• Weight gain is a common and well-documented side effect 1, 4, 5
• Weight gain at 6 months is a strong predictor of future excessive weight gain with ongoing DMPA use 1, 2
• Studies suggest that patients showing early weight gain (>5% at 6 months) may experience significant increases in BMI with continued use 2
• Increased body fat mass occurs with DMPA use 4

Bone Mineral Density Loss

• DMPA causes reductions in bone mineral density (BMD), prompting the FDA to issue a black-box warning 1, 2
• Substantial recovery of BMD occurs after discontinuation of DMPA 1, 2
• All patients using DMPA should receive calcium (1300 mg daily) and vitamin D (600 IU daily) supplementation 1, 2
• Regular weight-bearing exercise is recommended to mitigate bone density loss 2
• The American College of Obstetricians and Gynecologists does not advise limiting DMPA use to 2 years, recognizing that benefits of preventing unwanted pregnancy generally outweigh risks 1, 2

Cardiovascular and Thromboembolic Risks

• Thromboembolic disorders including thrombophlebitis and pulmonary embolism have been reported 3, 5
• Women using DMPA should be monitored for signs of thromboembolism 1
• Deep and superficial venous thrombosis, pulmonary embolism, myocardial infarction, and stroke are documented adverse reactions 3
• History of stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis are contraindications to use 6

Breast-Related Side Effects

• Breast tenderness (mastodynia) is common 3, 5
• Breast milk secretion (galactorrhea) may occur 3
• Breast pain and enlargement have been reported 3

Neuropsychiatric Effects

• Mental depression, insomnia, somnolence, dizziness, headache, and nervousness are documented 3
• Inconsistent evidence exists for an association between DMPA use and mood or libido changes 4
• Changes in libido may occur with continued use 2

Gastrointestinal Effects

• Nausea is a common side effect 3
• Abdominal cramps and bloating occur 3
• Cholestatic jaundice has been reported 3

Dermatologic Effects

• Acne, alopecia (hair loss), and hirsutism (hair growth) have been reported 3
• Sensitivity reactions including urticaria, pruritus, edema, and generalized rash occur 3

Ophthalmologic Effects

• Neuro-ocular lesions including retinal thrombosis and optic neuritis have been reported 3
• Changes in vision and sensitivity to contact lenses may occur 3

Fertility Effects

• Long-term DMPA use is associated with delayed return to fertility, typically 9 to 18 months after discontinuation 2
• This delay occurs while the endometrial lining returns to its pre-DMPA state and ovulatory function returns 2

Serious Adverse Reactions Requiring Immediate Medical Attention

Call healthcare provider immediately for: 3

• New breast lumps
• Unusual vaginal bleeding
• Changes in vision or speech
• Sudden new severe headaches
• Severe chest or leg pains with or without shortness of breath
• Memory loss or confusion
• Hives, breathing problems, or swelling of face, mouth, tongue, or neck (anaphylaxis)

Clinical Management Strategies

• Schedule follow-up visits every 11-12 weeks for adolescents (rather than every 13 weeks) to allow for missed or delayed visits 1
• Monitor weight changes, especially during the first 6 months of use 1
• Consider alternative contraceptive methods if significant weight gain occurs within first 6 months 1
• Discuss lifestyle modifications to manage weight gain 1
• Ensure calcium and vitamin D supplementation for all patients 1, 2

Common Pitfalls to Avoid

• Failing to counsel patients about expected menstrual changes before initiating DMPA leads to higher discontinuation rates 1
• Not monitoring weight changes, especially during the first 6 months of use 1
• Overlooking the importance of calcium and vitamin D supplementation for bone health 1
• Unnecessarily limiting use to 2 years when other contraceptive options are inadequate 1, 2