Originally published as JCO Early Release 10.1200/JCO.2008.20.0923 on June 8 2009

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Impact of Androgen Deprivation Therapy on Cardiovascular Disease and Diabetes

From the Division of General Internal Medicine & Clinical Epidemiology and Osteoporosis Program, University Health Network; Geriatric Program, Toronto Rehabilitation Institute; Departments of Medicine, Health Policy, Management and Evaluation, Surgery, and Radiation Oncology, University of Toronto; and the Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.

Corresponding author: Shabbir M.H. Alibhai, University Health Network, Room EN14-214, 200 Elizabeth St, Toronto, Ontario, Canada, M5G 2C4; e-mail: shabbir.alibhai{at}uhn.on.ca.

Purpose Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort.

Methods Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined.

Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio [HR], 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes.

Conclusion Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.

Supported in part by the Toronto General & Toronto Western Research Foundation and a research scientist award from the Canadian Cancer Society (S.M.H.A.) and by a midcareer scientist award from the Canadian Institutes of Health Research (A.M.C.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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