Contraceptive use and fracture risk in active-duty females - A case control study

Abstract: Objective: To determine the association of hormonal contraception use with military member stress fractures given service women are at higher risk than men, impacting readiness, and the hypothesized increased risk of fracture with continuous contraceptive use while deployed. Study Design: This IRB approved case-control study used incidence density sampling to assess the association between prescribed hormonal contraceptives and incident stress fracture diagnosis. Up to four controls were matched to each case of stress fracture based on race/ethnicity, service branch, age (within one year), and time in service category. Cases with < four months of service were excluded. Crude and adjusted incidence rate ratios and associated 95% confidence intervals (CIs) were calculated using proportional hazards models to estimate the effect of hormonal contraceptive use within two years prior to incident stress fracture diagnosis. IUDs, implants, and injectables were analyzed separately and oral contraceptives, patches, and vaginal rings were analyzed combined given their similar biologic mechanisms. The final multivariable models adjusted for the matched groups, rank, and obesity. Results: Cases (n= 1,689) were more likely to be enlisted, vitamin D deficient, obese, and have a history of bone disease. Before adjustment for obesity and rank, no hormonal contraceptives were associated with increased risk of fracture. After adjustment for obesity and rank, only the combination of oral contraceptives/patches/vaginal rings demonstrated a statistically significant association with stress fracture after two to three years of use (IRR 2.17, 95% CI 1.10-4.28, p value 0.03). Conclusions: Our study suggests limited or no associations between recent hormonal contraceptive use and increased risk for stress fracture in military service members. The potential association between oral contraceptives/patches/vaginal rings and stress fracture should be investigated further. This study finds that hormonal contraceptive use is not associated with an increased risk of stress fracture in active duty female servicemembers. This study supports knowledge of hormonal effects on bone and prescribing considerations in highly active women.