The long and tortuous history of the discovery of testosterone and its clinical application.
BACKGROUND
The testis importance in homeostasis was recognized for millennia, but a consistent interest in exploring their endocrine function only goes back to about a century.


OBJECTIVE
The aim of this study is to provide a succinct perspective of the events leading to the discovery of testosterone, the mind-boggling early attempts at therapy and today's situation.


METHODS
The literature was reviewed with searches in OvidSP Medline, PubMed, and Google Scholar under the headings of testosterone/androgens history. Due to the explosion of reports between the late 19th and early 20th centuries, a manual review of the collection of the period's journals at the university's library was performed. Pertinent books were consulted for specific biographical details.


RESULTS
There is a robust body of literature dealing with testicular function for the period starting in the late 1800s. It is illustrative to learn the painful efforts of many well-intentioned and honest scientists with more conviction and determination than knowledge. Among them, unfortunately, a number of charlatans and profiteers tainted the concept of hypogonadism and its treatment with repercussions lasting until this day. The discovery and synthesis of testosterone represent the effort of brilliant minds (two Nobel Prizes) in various countries and frequently working for the pharmaceutical industry. Shortly after testosterone became available, controversy arose about its application, use, abuse, and potential detrimental effects. Over the decades, the hullabaloo about hypogonadism and its treatment has focused on a variety of issues ranging from absurd efficacy claims to solid studies and from doubts of its existence to convincing proof of a detrimental age-associated deficit in testosterone production.


CONCLUSIONS
The history of testosterone discovery, synthesis, and introduction into the therapeutic armamentarium is an outstanding example of human curiosity, ingenuity, greed, and skepticism. Despite the vast progress in the field, many issues remain unresolved, but thoughtful science augurs well for its future.
Department of Urology, Queen's University, Kingston, ON, Canada. moralesa@queensu.ca
Alvaro
A
Morales
D000728:Androgens / Q000627:therapeutic use; D055808:Drug Discovery / Q000266:history; D049671:History, 18th Century; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy; D008297:Male; D009613:Nobel Prize; D013737:Testis / Q000637:transplantation; D013739:Testosterone / Q000172:deficiency / Q000266:history* / Q000627:therapeutic use; D014183:Transplantation, Heterologous / Q000266:history
D000728:Androgens; D013739:Testosterone