Androgen-deprivation therapy for nonmetastatic prostate cancer is associated with an increased risk of peripheral arterial disease and venous thromboembolism

Eur Urol. 2012 Jun;61(6):1119-28. doi: 10.1016/j.eururo.2012.01.045. Epub 2012 Feb 1.


Background: Previous studies demonstrate that androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and orchiectomy for prostate cancer (PCa) is associated with cardiovascular disease. However, few studies have examined its effect on the peripheral vascular system.

Objective: To study the risk of peripheral artery disease (PAD) and venous thromboembolism associated with ADT for PCa.

Design, settings, and participants: This was a population-based observational study of 182 757 US men ≥ 66 yr of age who were diagnosed with nonmetastatic PCa from 1992 to 2007, with a median follow-up of 5.1 yr, of whom 47.8% received GnRH agonists and 2.2% orchiectomy.

Measurements: We used Cox proportional hazards models with time-varying treatment variables to adjust for demographic and tumor characteristics in assessing whether treatment with GnRH agonists or orchiectomy were associated with PAD and/or venous thromboembolism.

Results and limitations: GnRH agonist use was associated with an increased risk of incident PAD (adjusted hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.12-1.21) and incident venous thromboembolism (adjusted HR: 1.10; 95% CI, 1.04-1.15). In addition, orchiectomy was associated with an increased risk of peripheral arterial disease (adjusted HR: 1.13; 95% CI, 1.02-1.26) and venous thromboembolism (adjusted HR: 1.27; 95% CI, 1.11-1.45). Limitations include the observational study design and the inability to assess the use of oral antiandrogens.

Conclusions: ADT for nonmetastatic PCa is associated with an increased risk of PAD and venous thromboembolism. Additional research is needed to better understand the potential risks and benefits of ADT, so that this treatment can be targeted to patients for whom the benefits are clearest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / adverse effects*
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Incidence
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / surgery
  • Neoplasms, Hormone-Dependent / therapy*
  • Orchiectomy / adverse effects*
  • Patient Selection
  • Peripheral Arterial Disease / epidemiology*
  • Proportional Hazards Models
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / epidemiology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / therapy*
  • Risk Assessment
  • Risk Factors
  • SEER Program
  • Time Factors
  • United States / epidemiology
  • Venous Thromboembolism / epidemiology*


  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone