LUTEINIZING HORMONE-RELEASING HORMONE AGONIST EFFECTS ON SKELETAL MUSCLE: HOW HORMONAL THERAPY IN PROSTATE CANCER AFFECTS MUSCULAR STRENGTH

ABSTRACT Purpose: Since the discovery of Huggins in 1941 demonstrating the androgen dependence of prostate cancer cells, the use of pharmacological therapies to decrease systemic androgen concentrations has been one of the main treatment options for prostate cancer. Despite their efficacy luteinizing hormone releasing hormone agonists (LHRHas) have a number of side effects, of which many have not been fully investigated in humans. This review focuses on the effects of LHRHas on skeletal muscle in 3 main areas, namely effects at the androgen receptor, at the neuromuscular junction and on skeletal muscle myofibers. Since prostate cancer is predominantly a disease of elderly individuals, the aging effects of LHRHa therapy on skeletal muscle are magnified and of clinical importance. Materials and Methods: A comprehensive MEDLINE search was performed of pertinent studies in the literature relating to the use of LHRHa and skeletal muscle. Results: LHRHas affect 3 primary sites within the skeletal muscle system, namely androgen receptor, the neuromuscular junction and second messenger systems, including insulin-like growth factor-1. All sites have been demonstrated to lead to a decrease in isokinetic exercise strength in large muscle groups. Conclusions: The musculoskeletal effects of LHRHas for the treatment of prostate cancer should be counteracted via a program of exercise strength training to decrease the morbidity associated with skeletal muscle weakness.