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

Side Effects of Depo-Provera (Medroxyprogesterone Acetate)

Depo-Provera causes several common side effects that patients must understand before initiation, with menstrual irregularities, weight gain, and bone mineral density loss being the most significant concerns. 1, 2

Most Common Side Effects

Menstrual Irregularities

• Nearly all patients initially experience menstrual cycle changes, including irregular bleeding, spotting, heavy bleeding, or lighter periods 1, 2
• These changes typically improve over time, with 55% of women experiencing complete amenorrhea (no bleeding) after one year and 68% after two years 2
• Pre-injection counseling about these menstrual changes significantly improves continuation rates 1
• Most adolescents who discontinue due to irregular bleeding do so after only one injection, highlighting the importance of early counseling 3

Weight Gain

• Approximately two-thirds of women gain about 5 pounds during the first year of use 2
• Average weight gain reaches 8 pounds over two years of continuous use 2
• Early weight gain (>5% at 6 months) strongly predicts continued excessive weight gain with ongoing use 1, 4
• Among adolescents, 21% experience early weight gain and continue gaining weight over 18 months 1

Other Frequent Side Effects

• Headache 2, 5
• Abdominal pain or discomfort 2
• Nervousness and dizziness 2
• Weakness and tiredness 2
• Breast tenderness (mastalgia) 4, 5
• Hair loss 4
• Changes in libido 4

Serious Side Effects Requiring Immediate Medical Attention

Bone Mineral Density Loss

• Depo-Provera causes progressive loss of calcium from bones, with greater loss occurring with longer duration of use 2
• The FDA issued a black box warning in 2004 regarding BMD loss 4
• Bone density may not completely recover after discontinuation, particularly in adolescents who used the method for more than 2 years 1
• Despite these concerns, the American College of Obstetricians and Gynecologists does not recommend limiting use to 2 years, as benefits of preventing pregnancy generally outweigh risks 1, 4
• All patients must receive counseling on skeletal health measures: 1,300 mg daily calcium intake, 600 IU daily vitamin D, regular weight-bearing exercise, and smoking cessation 1, 6

Cardiovascular and Thromboembolic Events

• Blood clots in arms, legs, lungs, and eyes 2
• Stroke 2
• Sudden severe headache, vomiting, dizziness, fainting, vision or speech problems, weakness, or numbness in extremities warrant immediate evaluation 2
• Severe pain or swelling in the calf may indicate deep vein thrombosis 2

Breast Cancer Risk

• Women using Depo-Provera may have a slightly increased risk of breast cancer compared to non-users 2
• Long-term data has established that DMPA does not increase risk of other gynecologic malignancies 7

Other Serious Complications

• Ectopic pregnancy (pregnancy outside the uterus) is a medical emergency requiring immediate attention 2
• Severe allergic reactions including hives, difficulty breathing, and swelling of face, mouth, tongue, or neck 2
• Yellowing of eyes or skin (jaundice) 2
• Persistent pain, pus, or bleeding at injection site 2

Delayed Return to Fertility

• Return to fertility is typically delayed 9-18 months after discontinuation, regardless of injection formulation (intramuscular or subcutaneous) 4, 6
• This delay occurs while the endometrial lining and ovulatory function return to normal 4

Clinical Pitfalls to Avoid

• Do not discontinue Depo-Provera at 2 years based solely on duration concerns, as this increases risk of unintended pregnancy without clear benefit 6
• Do not routinely order bone density scans after 2 years unless additional osteoporosis risk factors are present 6
• Counsel patients extensively before the first injection about menstrual changes and weight gain, as 70% of adolescents who discontinue due to irregular bleeding do so after only one injection 3
• Monitor weight at 6 months, as early gainers (>5% increase) will likely continue excessive weight gain 4, 6
• Recognize that 37% of discontinuers may restart the method, with highest restart rates among those who stopped due to missed appointments (87%) rather than side effects 3
• Be aware that 19% of adolescent discontinuers become pregnant, warranting close follow-up after stopping Depo-Provera 3