Metabolic complications of androgen deprivation therapy for prostate cancer

Abstract

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(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.

Figure 1

GnRH agonist associated sarcopenic obesity. GnRH agonists increase abdominal cross-sectional area primarily through accumulation of subcutaneous fat. Cross-sectional images of young healthy man (A) and of obese man receiving long-term GnRH agonist therapy (B). Note relative paucity of abdominal and paraspinal musculature, and accumulation of subcutaneous fat.

Figure 2

Insulin sensitivity decreases during GnRH agonist therapy. Glucose and insulin levels throughout oral glucose tolerance test. Data are taken at baseline (circles) and after 12 weeks of androgen blockade (squares).

Figure 3

GnRH agonists are associated with significant excess risk of diabetes, coronary heart disease, myocardial infarction and sudden death. Largest excess risk is for diabetes (44%).