Use of Depot Medroxyprogesterone Acetate and Fracture Risk

Context: Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited. Objective: We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk. Design: We conducted a case-control analysis using the United Kingdom-based General Practice Research Database. Setting and Participants: Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008. Main Outcome Measures: Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders. Results: We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and1.54(95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (>2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1. Conclusions: This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures. (J Clin Endocrinol Metab 95: 4909-4916, 2010)