What side effects should patients with a history of depression, anxiety, or other mental health conditions be warned about when taking Depo-Provera (medroxyprogesterone acetate)?

Key Side Effects to Warn Patients About When Prescribing Depo-Provera

Patients should be warned about menstrual irregularities (including amenorrhea), weight gain, bone mineral density loss with prolonged use, delayed return to fertility, and the need for STI protection, with special attention to monitoring for mood changes in those with mental health histories. 1

Critical Warnings Required by FDA

Bone Mineral Density Loss

• Depo-Provera carries an FDA black box warning about bone mineral density (BMD) loss, particularly concerning for adolescents and young adults during critical bone-building years 1
• Counsel patients that BMD loss occurs during use but is largely reversible after discontinuation, though complete recovery may not occur in all patients 2, 1
• Advise daily calcium supplementation (1,300 mg) and vitamin D (600 IU), along with weight-bearing exercise and smoking cessation 2
• Despite the black box warning, current guidelines do not restrict use to 2 years, as pregnancy prevention benefits generally outweigh BMD risks 2

Menstrual Changes (Most Common Side Effect)

• Irregular bleeding, spotting, and amenorrhea are the most common side effects and the primary reason for discontinuation 1, 3
• By 12 months, 55% of users experience amenorrhea; by 24 months, 68% become amenorrheic 1
• 70% of adolescents who discontinue due to irregular bleeding do so after only one injection 3
• Emphasize that irregular bleeding typically improves with continued use and amenorrhea is not harmful 1

Weight Gain

• Weight gain is common and progressive: average 5.4 lbs at 1 year, 8.1 lbs at 2 years, 13.8 lbs at 4 years, and 16.5 lbs at 6 years 1
• Weight gain >5% at 6 months strongly predicts future excessive weight gain 2
• Weight gain is the second most common reason for discontinuation after menstrual irregularities 3

Delayed Return to Fertility

• Median time to conception after discontinuation is 10 months (range 4-31 months), unrelated to duration of use 1
• 68% of women who conceive do so within 12 months, 83% within 15 months, and 93% within 18 months after the last injection 1
• This delay is critical information for patients planning future pregnancies 1

Special Warnings for Patients with Mental Health Histories

Depression Monitoring

• The FDA label specifically states: "Monitor patients who have a history of depression and do not re-administer medroxyprogesterone acetate if depression recurs" 1
• One study found that women who continued Depo-Provera had lower baseline depressive symptom scores than discontinuers, and continuing users showed slight improvement in scores at 1 year 4
• However, the FDA warning takes precedence: active monitoring is mandatory for patients with depression history 1

Additional Important Side Effects

Cardiovascular and Thromboembolic Risks

• Warn about potential blood clots in arms, legs, lungs, and eyes 1
• Stroke risk, particularly in patients with additional risk factors 1
• History of stroke, MI, pulmonary embolism, or DVT are absolute contraindications 5, 1

Cancer Risks

• Recent users (within past 5 years) who used DMPA for ≥12 months may have slightly increased breast cancer risk 1
• Based on SEER data, this would increase breast cancer incidence from about 72 to 144 cases per 100,000 women ages 20-49 1
• Non-significant increased risk of invasive squamous-cell cervical cancer in women first exposed before age 35 1

Other Notable Side Effects

• Anaphylaxis and anaphylactoid reactions have been reported; emergency treatment must be available 1
• Injection site reactions, including persistent reactions from inadvertent subcutaneous administration 1
• Rare convulsions (association with drug use unclear) 1
• Decreased glucose tolerance requiring monitoring in diabetic patients 1
• Fluid retention affecting patients with epilepsy, migraine, asthma, or cardiac/renal dysfunction 1

Critical Counseling Points

STI Protection

• Depo-Provera provides no protection against HIV/AIDS or other sexually transmitted infections 1
• Condom use must be emphasized at all times 6

Ectopic Pregnancy Risk

• Alert patients to seek immediate care for severe abdominal pain, as ectopic pregnancy risk exists 1

Follow-Up Requirements

• Annual visits for blood pressure monitoring and general healthcare 1
• No routine blood work or bone density scans needed unless additional risk factors present 2

Common Pitfalls to Avoid

• Do not discontinue Depo-Provera at 2 years based solely on duration concerns, as this increases unintended pregnancy risk without clear benefit 2
• Do not minimize menstrual irregularities during counseling—this is the primary reason for discontinuation and requires thorough pre-treatment discussion 3
• Do not fail to provide aggressive management of side effects, as this significantly improves continuation rates 3
• For patients with depression history, establish a specific monitoring plan before initiation rather than generic reassurance 1