Morgentaler A, Traish A. The History of testosterone and the Evolution of its Therapeutic Potential. Sexual medicine reviews. The History of Testosterone and the Evolution of its Therapeutic Potential Introduction - Testosterone therapy has been controversial since its synthesis in the 1930s to the present day. Testosterone’s history provides depth and context for current controversies. Aim - To review the history of testosterone therapy from its initial synthesis in the 1930s to the modern day. Methods - Expert review of the literature. Main Outcome Measures - Impactful events in the history of testosterone. Results - By the 1940s there was already a fascinating literature that described the many symptomatic benefits of testosterone therapy that are recognized today. Numerous early reports suggested testosterone therapy improved angina pectoris and peripheral vascular disease. The assertion by Huggins and Hodges (Cancer Res 1941;1:293–297) in 1941 that testosterone activated prostate cancer (PCa) cast a pall for the next 70 years. The introduction of the radioimmunoassay in the 1970s shifted the diagnosis of testosterone deficiency from signs and symptoms to an undue emphasis on blood test results. The fear of PCa was the primary obstacle to the adoption of testosterone therapy for decades. Prescription rates increased as accumulated evidence showed testosterone therapy was not associated with increased PCa risks. The observation that androgenic stimulation of PCa reaches a maximum at relatively low testosterone concentrations—the saturation model—provided the theoretical framework for understanding the relation between androgens and PCa and led to multiple case series documenting reassuring results of testosterone therapy in men with PCa. Recent concerns regarding cardiovascular risks also have diminished because new evidence suggests testosterone therapy might actually be cardioprotective. In 2016 the Testosterone Trials provided high-quality evidence of multiple benefits of testosterone therapy, nearly all of which had been recognized by clinicians by 1940. Conclusions - If the past has any lessons for the future, it is likely that research will continue to demonstrate health benefits of testosterone therapy, while it remains one of the most controversial topics in medicine.