What is the risk of osteoporosis in a woman using depot medroxyprogesterone acetate (Depo‑Provera), particularly with continuous use longer than two years?

Risk of Osteoporosis with Depo-Provera Use

Depo-Provera (DMPA) causes significant bone mineral density loss during use, particularly in the first 2 years, but this bone loss is largely reversible after discontinuation and does not require limiting use to 2 years in most patients. 1

Mechanism and Magnitude of Bone Loss

• DMPA reduces serum estrogen levels, which triggers bone mineral density (BMD) loss as bone metabolism accommodates to lower estrogen levels 2
• The FDA issued a black-box warning in 2004 regarding decreased BMD among DMPA users 1, 2
• In adult women using DMPA for up to 5 years, mean BMD decreases of 5-6% at the spine and hip occur, with the most pronounced decline during the first 2 years of use 2
• Specific BMD losses at the lumbar spine are: -2.86% at 1 year, -4.11% at 2 years, -4.89% at 3 years, -4.93% at 4 years, and -5.38% at 5 years 2
• After the first 2 years, bone loss stabilizes to less than 1% per year, essentially mirroring physiological bone loss 3

Reversibility of Bone Loss

• Substantial recovery of BMD occurs after DMPA discontinuation, with bone density returning toward or to baseline values 1, 4
• Recovery begins as early as 24 weeks after stopping therapy and persists for as long as women are followed 4
• After 5 years of DMPA use followed by 2 years post-discontinuation, mean BMD recovery shows: lumbar spine -3.13%, total hip -1.34%, and femoral neck -5.38% (compared to -5.38%, -5.16%, and -6.12% at 5 years respectively) 2
• Past DMPA users have BMD similar to never-users after discontinuation 4

Clinical Fracture Risk

The evidence on actual fracture risk is mixed but concerning for long-term users:

• A large UK case-control study found that DMPA exposure with 3-9 prescriptions increased fracture risk (OR 2.41,95% CI 1.42-4.08) compared to non-users 5
• The highest fracture risk was in women under 30 years with ≥10 prescriptions (OR 3.04,95% CI 1.36-6.81) 5
• Women in late reproductive years with past DMPA use also showed elevated fracture risk (OR 1.72,95% CI 1.13-2.63) 5
• However, a study of long-term users (mean 7 years) found relatively preserved BMD with age-matched values of 96-100% across skeletal sites 3

Current Guideline Recommendations

The American College of Obstetricians and Gynecologists (ACOG) does not advise limiting DMPA use to 2 years or routinely monitoring bone density, recognizing that the risk of unwanted pregnancy from limiting contraceptive options may outweigh bone concerns 1

• DMPA should be used as long-term contraception (>2 years) only if other methods are inadequate 2
• BMD should be evaluated when a woman needs to continue DMPA long-term 2
• Consider alternative contraceptive methods in women with osteoporosis risk factors including: metabolic bone disease, chronic alcohol/tobacco use, anorexia nervosa, strong family history of osteoporosis, or chronic use of anticonvulsants or corticosteroids 2

Essential Counseling and Mitigation Strategies

All DMPA users should receive counseling about skeletal health measures: 1

• Daily calcium intake of 1300 mg 1
• Daily vitamin D intake of 600 IU 1
• Regular weight-bearing exercise 1
• Avoidance of smoking and excessive alcohol 1

Special Population Considerations

Adolescents warrant particular concern because DMPA use during adolescence and early adulthood—a critical period of bone accretion—may reduce peak bone mass, though it remains unknown if this increases osteoporotic fracture risk in later life 2

• Preliminary data show adolescents (12-18 years) experience significant BMD decline from baseline with DMPA use 2
• In adolescents, BMD interpretation should account for patient age and skeletal maturity 2

Critical Clinical Pitfall

The most common error is unnecessarily limiting DMPA duration to 2 years based on outdated guidance. Current evidence supports that while BMD loss occurs, it is largely reversible, and ACOG explicitly states not to limit use to 2 years when DMPA is the most appropriate contraceptive option for the patient 1. The risk of unintended pregnancy from switching to less effective methods often outweighs theoretical long-term bone concerns in most women without additional osteoporosis risk factors.