Review of major adverse effects of androgen‐deprivation therapy in men with prostate cancer

• Published in: Cancer 2009-06, Vol.115 (11), p.2388-2399
• Main Authors: Taylor, Lockwood G., Canfield, Steven E., Du, Xianglin L.
• Format: Article
• Language: English
• Subjects: Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; androgen‐deprivation therapy; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; cardiovascular disease; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - mortality; Clinical Trials as Topic; Diabetes Mellitus - etiology; fracture; Fractures, Bone - chemically induced; Humans; Male; Medical sciences; Nephrology. Urinary tract diseases; osteoporosis; Osteoporosis - chemically induced; prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Quality of Life; Risk Assessment; side effects; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24283

Androgen‐deprivation therapy (ADT) is a common treatment for men with prostate cancer. Although ADT is effective at suppressing prostate‐specific antigen (PSA), stabilizing disease, alleviating symptoms in advanced disease, and potentially prolonging survival, it is not without serious side effects. However, to the authors' knowledge, there is lack of a systematic review of its major adverse effects to date. The authors of this report systematically reviewed and quantitatively assessed the literature on skeletal and cardiac side effects associated with ADT in men with prostate cancer. The PubMed database was searched for relevant published articles from 1966 to May 2008, and 683 articles were reviewed systematically from an original 20 different Medical Subject Heading search combinations. The focus of the review was on bone‐related and cardiovascular‐related outcomes. When appropriate, results were pooled from articles on specific adverse outcomes, summary risk estimates were calculated, and tests of heterogeneity were performed. Fourteen articles were identified that met inclusion criteria from the original 683 studies. Men who underwent ADT for prostate cancer had a significantly increased risk of overall fracture of 23% (summary relative risk, 1.23; 95% confidence interval [95% CI], 1.10‐1.38) compared with men who had prostate cancer but who did not undergo ADT. Furthermore, men who underwent ADT had a 17% increase in cardiovascular‐related mortality compared with men who did not undergo with ADT (summary hazards ratio, 1.17; 95% CI, 1.07‐1.29). Significant elevations in the risk of diabetes also were observed from 2 large studies. ADT was associated with an increased risk of skeletal fracture, incident diabetes, and cardiovascular‐related mortality, although the absolute risk of these events was low. Preventive measures against these adverse effects and careful assessment of patient's baseline health status should be considered. Cancer 2009. © 2009 American Cancer Society. This systematic review and quantitative assessment of the literature on the skeletal and cardiac side effects associated with androgen‐deprivation therapy (ADT) in men with prostate cancer indicated that ADT therapy is associated with an increased risk of skeletal fracture, incident diabetes, and cardiovascular‐related mortality, although the absolute risk of these events is low. Preventive measures against these adverse effects as well as careful assessment of patient's baseline h