Metabolic Complications of Androgen Deprivation Therapy for Prostate Cancer

Purpose

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.

Materials and Methods

We reviewed the medical literature using the PubMed® 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.

Key Words: prostatic neoplasms, gonadotropin-releasing hormone agonists, cardiovascular diseases, diabetes mellitus, obesity

Abbreviations and Acronyms: ADA, American Diabetes Association, ADT, androgen deprivation therapy, AHR, adjusted hazard ratio, BMI, body mass index, CaPSURE, Cancer of the Prostate Strategic Urologic Research Endeavor, CHD, coronary heart disease, CV, cardiovascular, EORTC, European Organization for the Research and Treatment of Cancer, FPG, fasting plasma glucose, GnRH, gonadotropin-releasing hormone, HDL, high density lipoprotein, IFG, impaired fasting glucose, IGT, impaired glucose tolerance, LDL, low density lipoprotein, MI, myocardial infarction, NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III, OGTT, oral glucose tolerance test, PSA, prostate specific antigen, RT, radiation therapy, RTOG, Radiation Therapy Oncology Group, SCD, sudden cardiac death, SEER, Surveillance, Epidemiology and End Results