Use of depot medroxyprogesterone acetate contraception and incidence of bone fracture

OBJECTIVE: Depot medroxyprogesterone acetate (DMPA) reversibly reduces bone mineral density. To estimate the extent to which DMPA might increase fracture risk, we undertook a retrospective cohort study of fractures in DMPA users and users of non-DMPA contraceptives, using the General Practice Research Database.

METHODS: Eligible women were aged younger than 50 years at the qualifying first contraceptive prescription. The DMPA users were classified by DMPA exposure (cumulative and time of last dose) based on prescription records. All incident fractures were included; fracture incidence and risk factors before starting contraceptive use (DMPA or other) also were estimated.

RESULTS: We identified 11,822 fractures in 312,395 women during 1,722,356 person-years of follow-up. Before contraceptive use started, DMPA users had higher fracture risk than nonusers (incidence rate ratio 1.28, 95% confidence interval [CI] 1.07–1.53). After DMPA started, crude fracture incidence was 9.1 per 1,000 person-years for DMPA users and 7.3 for nonusers (crude incidence rate ratio 1.23, 95% CI 1.16–1.30). Fracture risk in DMPA users did not increase after starting DMPA (incidence rate ratio after or before 1.08, 95% CI 0.92–1.26). There was little confounding by age or other factors that could be measured. Fracture incidence was 9.4 per 1,000 person-years in low-exposure DMPA users, and 7.8 per 1,000 in high-exposure DMPA users. The DMPA users had higher fracture risk than nonusers at the start of contraceptive use, with no discernible induction period.

CONCLUSION: Although DMPA users experienced more fractures than nonusers, this association may be the result of confounding by a pre-existing higher risk for fractures in women who chose DMPA for contraception.

LEVEL OF EVIDENCE: II