Author Response: Effects of Lifelong Testosterone Exposure on Health and Disease Using Mendelian Randomization

In 2020, a Mendelian randomization study was conducted on 161,268 males from the UK Biobank to investigate the effects of lifelong testosterone exposure on health and disease. The study found that increased free testosterone had both beneficial and adverse effects. Beneficial effects included increased bone mineral density and decreased body fat, while adverse effects included decreased HDL, increased risks of prostate cancer, androgenic alopecia, spinal stenosis, and hypertension. The study also found context-dependent effects on increased hematocrit and decreased C-reactive protein. No benefit was observed for type 2 diabetes, cardiovascular or cognitive outcomes. The researchers concluded that the benefits of long-term increased testosterone should be considered against adverse effects, notably increased prostate cancer and hypertension. They suggested that well-powered randomized trials are needed to conclusively address risks and benefits of testosterone treatment on these outcomes.