There are concerns about potential adverse events on the prostate, which remain major obstacles, especially when prescribing testosterone replacement therapy (TRT) in men with hypogonadism. This study explores prostate safety events using a randomized controlled design in hypogonadal men on testosterone replacement therapy. A total of 150 subjects enrolled were randomly assigned into either a TRT group or a placebo arm and were evaluated at a 6-month treatment period evaluation after baseline. The primary endpoints included prostate-specific antigen, prostate volume, and adverse events. Data show that the TRT participants had a significant regression in PSA levels (mean difference: 1.5 ng/mL, p < 0.01) compared to indications from placebo. On the other hand, there were no statistically significant changes in prostate volume or adverse events between the two groups. The current study points out the need to continue monitoring the prostate during testosterone treatment as well as the adoption of calls for precision medicine. Before this radical change can take place however prostate cancer prevention therapy TURP studies are warranted. These processes, supported by the current study's results, add knowledge to the growing body of information that calls to reconsider the usage of TRT.