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Androgen Deprivation Therapy in Prostate Cancer and Metabolic Risk for Atherosclerosis

Department of Internal Medicine (S.S.), Harbor Hospital of Baltimore, Baltimore, Maryland 21225; Consultant Endocrinologist (M.B.-B.), Baltimore, Maryland 21209; and Division of Endocrinology and Metabolism and Oncology (S.B.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21224

Address all correspondence and requests for reprints to: Shehzad Basaria, M.D., Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Suite 4300, Baltimore, Maryland 21224. E-mail: sbasari1{at}jhmi.edu.

Context: Prostate cancer (PCa) is the most common cancer in men. Androgen-deprivation therapy (ADT) is generally employed in the treatment of locally advanced and metastatic PCa. Although its use as an adjuvant therapy has resulted in improved survival in some patients, ADT has negative consequences. Complications like osteoporosis, sexual dysfunction, gynecomastia, and adverse body composition are well known. Recently, metabolic complications like insulin resistance, diabetes, dyslipidemia, and metabolic syndrome have emerged, which may be responsible for the increased cardiovascular mortality in this population.

Evidence Acquisition: A MEDLINE search was conducted for articles published over the last 20 yr based on the key words androgen deprivation therapy AND insulin resistance, hyperglycemia, diabetes, dyslipidemia, metabolic syndrome, and cardiovascular disease. Relevant studies in non-PCa populations evaluating the association between testosterone and metabolism were also reviewed and briefly mentioned where relevant.

Evidence Synthesis: Prospective studies evaluating early (3–6 months) metabolic changes of ADT show development of hyperinsulinemia; however, glucose levels remain normal. Cross-sectional studies of men undergoing long-term (12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. Furthermore, men undergoing ADT also experience higher cardiovascular mortality.

Conclusion: Long-term prospective studies of ADT are needed to determine the timing of onset of these metabolic complications and to investigate the mechanism behind them. In the meantime, we recommend baseline and serial screening for fasting glucose, lipids, and other cardiovascular risk factors in men receiving ADT. Glucose tolerance tests and cardiac evaluation may be required in selected cases.