Hopes for hormonal rejuvenation appear periodically throughout history—with the most prominent attempt occurring around the turn of the 20th century only to vanish in the 1930s following the discovery of testosterone, which discredited testis extracts and manipulations. In recent decades, there has been a renewed attempt for hormonal rejuvenation with testosterone in men.

Today, 8 decades since the first clinical use of testosterone,1 the sole unequivocal indication for testosterone treatment is as replacement therapy for men with pathological hypogonadism (ie, organic disorders of the reproductive system).2 Yet despite no proven new indications, global testosterone sales increased 100-fold over the last 3 decades, including increases of 40-fold in Canada and 10-fold in the United States from 2000-2011.3 This was achieved by marketing strategies that circumvented the need for efficacy and safety testing of testosterone for male aging by stretching the definition of the term hypogonadism to encompass virtually any condition associated with low circulating testosterone levels. Promoted under the rubric “low T” (also referred to as andropause or late-onset hypogonadism), this process was facilitated by individual physicians and professional societies that minimized the fundamental distinction between pathological hypogonadism and functional states (including aging) associated with low circulating testosterone levels.4