Metabolic complications of androgen deprivation therapy for prostate cancer.
OBJECTIVE
Androgen deprivation therapy has a variety of well recognized adverse effects including vasomotor flushing, loss of libido, fatigue, gynecomastia, anemia and osteoporosis. This review focuses on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease.


METHODS
We reviewed the medical literature using the PubMed(R) search terms prostate cancer, androgen deprivation therapy, gonadotropin-releasing hormone agonists, obesity, insulin resistance, lipids, diabetes, cardiovascular disease and myocardial infarction. We provide a focused review and our perspective on the relevant literature.


RESULTS
Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol.


CONCLUSIONS
Androgen deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms. Little is known about the optimal strategy to mitigate the adverse metabolic effects of androgen deprivation therapy. Thus, we recommend an emphasis on existing strategies for screening and treatment that have been documented to reduce the risk of diabetes and cardiovascular disease in the general population.
Saylor
Philip J
PJ
Department of Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. psaylor@partners.org
Smith
Matthew R
MR
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D050171:Dyslipidemias / Q000139:chemically induced / Q000453:epidemiology; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D018570:Risk Assessment
D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone