Depo-Provera and Cancer Risk
Depo-Provera (depot medroxyprogesterone acetate/DMPA) does not increase overall cancer risk in reproductive-age women and actually provides substantial protection against endometrial cancer, though recent or current users may have a modest, temporary elevation in breast cancer risk that disappears after discontinuation. 1
Breast Cancer Risk
Overall Risk Assessment
- The FDA drug label explicitly states that healthcare providers should counsel patients about the "possible increased risk of breast cancer" with DMPA use 1
- Pooled analysis of major case-control studies (1,768 breast cancer cases and 13,905 controls) found no overall increased risk of breast cancer in ever-users of DMPA (RR 1.1; 95% CI 0.97-1.4) 2
- No increase in breast cancer risk was observed with increasing duration of DMPA use 2
Recent/Current Users
- Women who started DMPA within the previous 5 years have an elevated relative risk of 2.0 (95% CI 1.5-2.8) 2
- This increased risk in recent users could reflect enhanced tumor detection in women using DMPA or acceleration of pre-existing tumor growth, rather than true cancer initiation 2
- Critically, women who used DMPA more than 5 years previously had no increase in breast cancer risk, regardless of their duration of use 2
Age-Specific Considerations
- Young women (ages 25-34) show a relative risk of 2.0 (95% CI 1.0-3.8) for any DMPA use 3
- Women who used DMPA for 2+ years before age 25 had an elevated risk (RR 4.6; 95% CI 1.4-15.1), though this represents a small number of women 3
- The overall pattern resembles that seen with combined oral contraceptives 4
Endometrial Cancer Protection
- DMPA use is associated with an 80% risk reduction in endometrial adenocarcinoma, providing even greater protection than oral contraceptives 4
- This represents a substantial benefit that should be weighed against any potential breast cancer concerns 4
Other Gynecologic Cancers
- DMPA use does not affect the risk of epithelial ovarian cancer 4
- DMPA use does not affect the risk of cervical neoplasia 4
- Long-term controlled clinical studies showed no increased risk for ovarian, liver, or cervical cancer 5
Clinical Recommendations
Counseling Approach
- Inform patients that DMPA provides strong protection against endometrial cancer while having a neutral-to-slightly-elevated breast cancer risk profile similar to oral contraceptives 1, 4
- Explain that any breast cancer risk elevation is temporary and confined to recent/current users, disappearing 5+ years after discontinuation 2
- Emphasize that the absolute risk remains low in reproductive-age women, even with the modest relative risk increase in recent users 2
Duration of Use
- The American College of Obstetricians and Gynecologists does not recommend restricting DMPA to 2 years, as the benefits of preventing unwanted pregnancy generally outweigh risks 6
- No time limit exists for DMPA use despite the FDA black box warning about bone mineral density loss 6
- For patients continuing beyond 2 years, counsel about skeletal health measures including calcium (1,300 mg daily), vitamin D (600 IU daily), weight-bearing exercise, and smoking cessation 6
Common Pitfalls
- Do not discontinue DMPA at 2 years based solely on duration concerns, as this increases risk of unintended pregnancy without clear benefit 6
- Do not overstate breast cancer risk—the association is modest, temporary, and comparable to oral contraceptives 2, 4
- Do not neglect to mention the substantial endometrial cancer protection, which is a major benefit of DMPA use 4
- Recognize that most women experience menstrual irregularities (57% amenorrhea by 1 year), which is not a health hazard but affects acceptability 5