AB004. Contemporary perspectives on testosterone replacement therapy (TRT)

The hormone testosterone (T) is responsible for the normal growth and development of male sex organs, and maintenance of secondary sex characteristics. T is the primary androgenic hormone, and its production and secretion are the end products of a series of hormonal interactions and feedback regulatory mechanisms. Testosterone deficiency (TD) occurs when the testes fail to produce normal levels of T. Primary, or hypergonadotropic, hypogonadism is recognized as testicular failure; T levels are low, and pituitary gonadotropins are elevated. In secondary, or hypogonadotropic hypogonadism, there is an inadequate secretion of pituitary gonadotropins, and, in addition to low serum T levels, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are low or low-normal. The role of T in cardiovascular (CV) disease in men is currently a hotly debated topic. Two recent studies suggest that hypogonadal men undergoing testosterone replacement therapy (TRT) have a higher incidence of CV morbidity and mortality. However, the preponderance of TRT studies conducted over the past 3 decades has demonstrated neutral or lower incidences of CV events. Perhaps the decreased risk with TRT can be attributed to the modification and improvement of CV risk factors. The FDA Advisory Committee convened a meeting on Sep 17, 2014 to further assess TRT and correctly opined that, “with regards to the risk of CV events, the evidence linking TRT to an increased risk of heart attack, stroke, and death was inconclusive.” They also suggested that the appropriate population for TRT be identified and that studies to better determine the risks of major CV events in men receiving TRT be conducted. Despite the results of the 800-elderly-man, NIH-sponsored, 5-year T-Trial to be published in the latter part of 2015, there is still a need for longer and larger randomized, placebo-controlled trials to provide more definitive and reassuring data regarding the efficacy and safety of TRT in symptomatic hypogonadal men.