Evaluation of the causality between testosterone, obesity, and diabetes

While the effect of testosterone on male sex characteristics is well-known, its relationship with non-communicable diseases (NCDs) – particularly obesity and type 2 diabetes (T2D) – is less concrete. Furthermore, testosterone may yield sex-specific results on such NCDs. We employed Mendelian randomization (MR) analysis on publicly available patients’ genomic data to evaluate the causality between testosterone, obesity, and T2D within combined, male, and female sex-stratified settings. Our results demonstrated that T2D significantly increased and was increased by heightened levels of obesity. Furthermore, we also found that male testosterone likely reduces obesity and T2D, while female testosterone significantly increases body fat and blood glucose levels. This research presents sex-based discrepancies that could hold significance in future clinical applications of testosterone. This research also highlights the potential in sex-stratifying two-sample MR analyses for future studies.