What are the side effects of Depoprovera (Depot Medroxyprogesterone Acetate, DMPA)?

Side Effects of Depo-Provera (DMPA)

Depo-Provera causes menstrual irregularities in nearly all patients initially, with weight gain, bone density loss, and delayed return to fertility being the most clinically significant side effects, though the method remains highly effective and safe for most women. 1

Common and Expected Side Effects

Menstrual Changes

• Irregular bleeding and spotting occur in nearly all patients during the first year of use, typically presenting as unpredictable episodes of spotting and bleeding 1, 2
• By 12 months of use, approximately 55% of women experience amenorrhea, increasing to 68% by 24 months 2
• These menstrual irregularities typically improve over time and are less likely to result in discontinuation if patients receive counseling before the first injection 1
• If abnormal bleeding persists or is severe, investigation should be instituted to rule out organic pathology 2

Weight Gain

• Weight gain is a common side effect that does not occur in all patients 1, 3
• Weight status at 6 months is a strong predictor of future excessive weight gain with ongoing DMPA use - patients gaining >5% of body weight at 6 months are at higher risk for significant BMI increases with continued use 1, 3
• Studies in both adolescents and adults confirm this pattern 1

Bone Mineral Density Loss

• DMPA causes reductions in bone mineral density (BMD), prompting an FDA black box warning in 2004 1, 2
• In adults, mean BMD decreases of approximately 5-6% occur at the spine, total hip, and femoral neck after 5 years of use 2
• Adolescents show similar patterns, with decreases of 2-6% at various skeletal sites, which is particularly concerning since this age group should be gaining bone density 2
• Substantial recovery of BMD occurs after discontinuation of DMPA, though longer duration of treatment is associated with less complete recovery during the 2-year post-therapy period 1, 3, 2
• The American College of Obstetricians and Gynecologists does not advise limiting DMPA use to 2 years or routinely monitoring bone density, as the benefits of preventing unwanted pregnancy generally outweigh the risks 1, 3
• All patients should be counseled about skeletal health measures: daily intake of 1300 mg calcium, 600 IU vitamin D, and regular weight-bearing exercise 1, 3

Delayed Return to Fertility

• Return to fertility is delayed after discontinuation, typically 9-18 months, which occurs while the endometrial lining returns to its pre-DMPA state and ovulatory function returns 3
• MPA can be detected in serum for as long as 9 months after a single 150 mg injection 4
• Ovulation resumes when MPA levels fall below 0.1 ng/mL 4
• This delay should be discussed with women planning pregnancy in the near future 3

Other Adverse Effects

Neurological and Systemic

• Headache may occur with continued use 1, 3
• Mood disturbances have been reported, though long-term data do not establish increased risk 5

Breast-Related

• Mastalgia (breast pain) may occur 1, 3
• Breast size typically does not change despite low estradiol levels 4

Other Effects

• Hair loss may occur 1, 3
• Changes in libido (increase or decrease) have been reported 1, 3

Serious but Rare Adverse Events

Thromboembolic Disorders

• Physicians should be alert to manifestations of thrombotic disorders including thrombophlebitis, pulmonary embolism, cerebrovascular disorders, and retinal thrombosis 2
• If these occur or are suspected, the drug should not be readministered 2

Anaphylaxis

• Anaphylaxis and anaphylactoid reactions have been reported with DMPA use 2
• Serious anaphylactic reactions require emergency medical treatment 2

Ocular Disorders

• Sudden partial or complete loss of vision, proptosis, diplopia, or migraine warrant immediate examination 2
• If papilledema or retinal vascular lesions are found, medication should not be readministered 2

Ectopic Pregnancy

• Healthcare providers should be alert to the possibility of ectopic pregnancy among DMPA users who become pregnant or complain of severe abdominal pain 2

Cancer Risk Considerations

Breast Cancer

• Long-term surveillance found slight or no increased overall risk of breast cancer 2
• A subgroup analysis showed increased risk (RR 2.19) in women whose first exposure was within the previous 4 years and who were under 35 years of age, though the overall relative risk for ever-users was only 1.2 2
• Current breast cancer is an absolute contraindication (Category 4) 6
• Past breast cancer with no evidence of disease for 5 years is a Category 3 condition (risks usually outweigh benefits) 6

Other Cancers

• No overall increased risk of ovarian, liver, or cervical cancer 2
• A prolonged protective effect reducing the risk of endometrial cancer has been demonstrated 2, 7
• Statistically insignificant increase in invasive squamous-cell cervical cancer risk has been associated with use in women first exposed before age 35 2

Effects on Lactation

• Detectable amounts of drug are identified in breast milk 2
• Milk composition, quality, and amount are not adversely affected 2
• Neonates and infants exposed through breast milk and followed through puberty showed no adverse developmental or behavioral effects 2

Clinical Pearls for Minimizing Side Effects

Pre-Treatment Counseling

• Counseling about menstrual irregularities before the first injection significantly reduces discontinuation rates 1
• Patients should understand that irregular bleeding typically improves over time and that amenorrhea is common and not harmful 1, 2
• Discuss the 6-month weight gain predictor to help patients monitor early weight changes 1, 3

Management of Bleeding Irregularities

• For spotting or light bleeding: NSAIDs for 5-7 days may be used 1
• Patients should be reassured they may contact their provider at any time to discuss bleeding or other side effects 1
• If the patient desires removal at any time, offer counseling on alternative methods 1

Bone Health Optimization

• All patients should receive counseling on calcium (1300 mg daily), vitamin D (600 IU daily), and weight-bearing exercise 1, 3
• Consider other risk factors for osteoporosis when evaluating long-term use 1, 3
• For patients with multiple osteoporosis risk factors, alternative contraceptive methods may be preferable 3