Androgen deprivation therapy for prostate cancer: new concepts and concerns

Abstract

The aim of this review is to summarize new concepts and concerns regarding treatment-related osteoporosis, diabetes, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Gonadotropin-releasing hormone agonists increase bone turnover, decrease bone mineral density, and increase fracture risk. Bisphosphonates, selective and estrogen receptor modulators significantly increase bone mineral density during androgen deprivation therapy. Ongoing randomized controlled trials will assess efficacy of denosumab, toremifene, and zoledronic acid to prevent fractures in this setting. Gonadotropin-releasing hormone agonists also increase fat mass, decrease insulin sensitivity, and increase serum lipoproteins. In contrast to the classical metabolic syndrome, however, the phenotype of men during androgen deprivation therapy is characterized by increased high-density lipoprotein cholesterol and preferential accumulation of subcutaneous fat. Gonadotropin-releasing hormone agonists are associated with greater risk of incident diabetes and cardiovascular disease in men with prostate cancer. Androgen therapy increases risk of fractures, diabetes mellitus, and cardiovascular disease in men with prostate cancer. Current and planned studies will evaluate strategies to prevent these treatment-related adverse effects.