Investigating the adverse drug reactions of testosterone using Mendelian randomization: a study protocol

Summary This protocol outlines a systematic review that aims to explore the adverse effects of testosterone exposure using Mendelian randomization studies. Testosterone plays an important role in numerous physiological processes, yet the causal relationships between testosterone levels and various health outcomes remain unclear, particularly in the context of testosterone therapy and anabolic-androgenic steroid misuse. Traditional observational studies are limited by confounding factors and reverse causality, while randomized controlled trials are challenging to conduct over the long-term. To overcome these limitations, this review will synthesize findings from Mendelian randomization studies, which use genetic variants as instrumental variables to infer causality between testosterone exposure and health outcomes. By focusing on Mendelian randomization methodology, the study seeks to provide insights into the long-term effects of testosterone on a wide range of health outcomes, including but not limited to cardiovascular health, cancer risk, metabolic conditions, and psychological disorders. Ultimately, this systematic review aims to provide a deeper understanding of the potential side effects of testosterone exposure, which may be relevant in the context of testosterone treatment or anabolic-androgenic steroid misuse.