Association Between 5-{alpha} Reductase Inhibition and Risk of Hip Fracture

Steven J. Jacobsen, MD, PhD; T. Craig Cheetham, PharmD, MS; Reina Haque, PhD; Jiaxiao M. Shi, PhD; Ronald K. Loo, MD

JAMA. 2008;300(14):1660-1664.

Context  For more than 15 years, 5-{alpha} reductase inhibitors, which block the conversion of testosterone to dihydrotestosterone, have been used in the treatment of benign prostatic hyperplasia (BPH).Short-term studies show no effects of these agents on bone metabolism,but long-term data are not available.

Objective  To assess the association between use of 5-{alpha} reductase inhibitors (eg, finasteride) for BPH and occurrence of hip fracture.

Design, Setting, and Patients  Population-based case-control study using data from Kaiser Permanente Southern California, a managed care organization with more than 3 million members. Case patients included 7076 men 45 years and older with incident hip fracture from 1997-2006. Control patients were 7076 men without incident hip fracture, optimally matched at a 1:1 ratio to case patients on age and medical center. Electronic information on pharmaceutical use was used to identify use of finasteride from 1991 forward.

Results  Overall, 2547 (36%) and 2488 (35%) case and control patients, respectively, had a diagnosis of BPH (P = .30), and 109 (1.5%) and 141 (2.0%) of case and control patients, respectively, had been exposed to finasteride prior to the index date (matched odds ratio, 0.77; 95% confidence interval, 0.59-1.00; P = .04). There was no suggestion of a dose-response relationship between exposure to 5-{alpha} reductase inhibitors when the exposure was stratified into tertiles of total exposure (P = .12). By contrast, there was a slightly higher prevalence of {alpha}-blocker use in case vs control patients (32% vs 30%, respectively; P = .04).

Conclusions  Exposure to 5-{alpha} reductase inhibitors was not associated with increased risk of hip fracture. The reduction in risk observed with exposure to 5-{alpha} reductase inhibitors and the modest increase in risk associated with exposure to {alpha}-blockers require replication and warrant further investigation.


Author Affiliations: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena (Drs Jacobsen, Haque, and Shi); Pharmacy Analytic Services, Kaiser Permanente Southern California, Downey (Dr Cheetham); and Department of Urology, Bellflower Medical Center, Kaiser Permanente Southern California, Bellfower (Dr Loo).