Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis.
BACKGROUND
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.


METHODS
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.


RESULTS
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 (> or =12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. Furthermore, men undergoing ADT also experience higher cardiovascular mortality.


CONCLUSIONS
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.
Shahani
Sadeka
S
Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Baltimore, MD 21224, USA.
Braga-Basaria
Milena
M
Basaria
Shehzad
S
D000465:Algorithms; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology*; D001823:Body Composition / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000401:mortality; D050171:Dyslipidemias / Q000139:chemically induced; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology*; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D012307:Risk Factors
D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal