Testosterone protects the lower urinary tract from metabolic syndrome-induced alterations

Abstract Epidemiological studies document a positive and independent association between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS). In the male, the pathogenesis of MetS-related LUTS involves a complex interplay among pathophysiological mechanisms mainly affecting the prostate and the bladder. Recently, hypogonadism has been recognized as a key factor bridging MetS and LUTS. Preclinical data have evidenced that MetS-induced hypogonadism is associated with alterations not only of the prostate but also of the bladder, and testosterone supplementation can counteract both. Interestingly, testosterone also shows a marked effect on the bladder, preventing the MetS-related RhoA/ROCK hyperactivation, which drives the pathogenesis of bladder overactivity and LUTS. The precise mechanisms through which testosterone exerts its protective action on the LUT remains to be fully elucidated; however, indirect (through improved cardiometabolic status) and direct (through local androgen receptor-mediated pathways) actions are both likely to play a role.