title: Androgen-deprivation therapy for nonmetastatic prostate cancer is associated with an increased risk of peripheral arterial disease and venous thromboembolism.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA. jhu2@partners.org
authors.forename: Jim C
authors.initials: JC
authors.lastname: Hu
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Williams
authors.forename: A James
authors.initials: AJ
authors.lastname: O'Malley
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Keating
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D009919:Orchiectomy / Q000009:adverse effects*; D018579:Patient Selection; D058729:Peripheral Arterial Disease / Q000453:epidemiology*; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D054556:Venous Thromboembolism / Q000453:epidemiology*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone