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

Jim C. Hu, Stephen Williams, A. James O'Malley, Matthew R. Smith, Paul L. Nguyen, Nancy L. Keating

Research output: Contribution to journalArticle

59 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)1119-1128
Number of pages10
JournalEuropean Urology
Volume61
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

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Peripheral Arterial Disease
Venous Thromboembolism
Androgens
Prostatic Neoplasms
Orchiectomy
Gonadotropin-Releasing Hormone
Confidence Intervals
Therapeutics
Observational Studies
Androgen Antagonists
Proportional Hazards Models
Blood Vessels
Cardiovascular Diseases
Demography
Research
Population
Neoplasms

Keywords

  • Hormonal/adverse effect
  • Peripheral vascular disease
  • Prostatic neoplasms/drug therapy
  • Venous thromboembolism

ASJC Scopus subject areas

  • Urology

Cite this

Androgen-deprivation therapy for nonmetastatic prostate cancer is associated with an increased risk of peripheral arterial disease and venous thromboembolism. / Hu, Jim C.; Williams, Stephen; O'Malley, A. James; Smith, Matthew R.; Nguyen, Paul L.; Keating, Nancy L.

In: European Urology, Vol. 61, No. 6, 06.2012, p. 1119-1128.

Research output: Contribution to journalArticle

Hu, Jim C. ; Williams, Stephen ; O'Malley, A. James ; Smith, Matthew R. ; Nguyen, Paul L. ; Keating, Nancy L. / Androgen-deprivation therapy for nonmetastatic prostate cancer is associated with an increased risk of peripheral arterial disease and venous thromboembolism. In: European Urology. 2012 ; Vol. 61, No. 6. pp. 1119-1128.
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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. 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.",
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AU - Williams, Stephen

AU - O'Malley, A. James

AU - Smith, Matthew R.

AU - Nguyen, Paul L.

AU - Keating, Nancy L.

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AB - 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.

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