Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer

J Clin Oncol. 2005 Nov 1;23(31):7897-903. doi: 10.1200/JCO.2004.00.6908.


Purpose: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density, a surrogate for fracture risk, in men with prostate cancer. We conducted a claims-based cohort study to characterize the relationship between GnRH agonists and risk for clinical fractures in men with nonmetastatic prostate cancer.

Patients and methods: Using medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group of men with nonmetastatic prostate cancer who initiated GnRH agonist treatment from 1992 to 1994 (n = 3,887). A comparison group of men with nonmetastatic prostate cancer who did not receive GnRH agonist treatment during the study period (n = 7,774) was matched for age, race, geographic location, and comorbidity. Clinical fractures were identified using inpatient, outpatient, and physician claims during 7 years of follow-up.

Results: In men with nonmetastatic prostate cancer, GnRH agonists significantly increased fracture risk. The rate of any clinical fracture was 7.88 per 100 person-years at risk in men receiving a GnRH agonist compared with 6.51 per 100 person-years in matched controls (relative risk, 1.21; 95% CI, 1.14 to 1.29; P < .001). Rates of vertebral fractures (relative risk, 1.45; 95% CI, 1.19 to 1.75; P < .001) and hip/femur fractures (relative risk, 1.30; 95% CI, 1.10 to 1.53; P = .002) were also significantly higher in men who received a GnRH agonist. GnRH agonist treatment independently predicted fracture risk in multivariate analyses. Longer duration of treatment conferred greater fracture risk.

Conclusion: GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Density / drug effects*
  • Cohort Studies
  • Fractures, Bone / epidemiology*
  • Gonadotropin-Releasing Hormone / agonists*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Incidence
  • Insurance Claim Review
  • Male
  • Osteoporosis / chemically induced
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Risk Factors
  • United States / epidemiology


  • Gonadotropin-Releasing Hormone