Misadventures in Toxicology: Concentration Matters for Testosterone-Induced Neurotoxicity

Testosterone is the predominant androgen in men and has important physiological functions. Due to declining testosterone levels from a variety of causes, testosterone replacement therapy (TRT) is increasingly utilized, while testosterone is also abused for aesthetic and performance-enhancing purposes. It has been increasingly speculated that aside from more well-established side effects, testosterone may cause neurological damage. However, the in vitro data utilized to support such claims is limited due to the high concentrations used, lack of consideration of tissue distribution, and species differences in sensitivity to testosterone. In most cases, the concentrations studied in vitro are unlikely to be reached in the human brain. Observational data in humans concerning the potential for deleterious changes in brain structure and function are limited by their inherent design as well as significant potential confounders. More research is needed as the currently available data are limited; however, what is available provides rather weak evidence to suggest that testosterone use or abuse has neurotoxic potential in humans.