Historical development of testosterone therapy

The first experimental proof that the testes produce a substance responsible for virility was provided by Berthold (1849). He transplanted testes from roosters into the abdomen of capons and recognized that the animals with the transplanted testes behaved like normal roosters: “They crowed quite considerably, often fought among themselves and with other young roosters and showed a normal inclination toward hens”. Berthold concluded that the virilizing effects were exerted by testicular secretions reaching the target organs via the bloodstream. Berthold's investigation is generally considered the origin of experimental endocrinology (Simmer and Simmer 1961). Following his observation various attempts were made to use testicular preparations for therapeutic purposes. The best known experiments are those by Brown-Séquard (1889), who tried testis extracts on himself which can at best have had placebo effects (Cussons et al. 2002). In the 1920s Voronoff transplanted testes from animals to humans for the purpose of rejuvenation (Voronoff 1920), but the effectiveness of his methods was disproven by a committee of the Royal Society London. The first testicular extracts with demonstrable biological activity were prepared by Loewe and Voss (1930) using the seminal vesicle as a test organ. Finally, the groundstone for modern androgen therapy was laid when steroidal androgens were first isolated from urine by Butenandt (1931), testosterone was obtained in crystalline form from bull testes by David et al. (1935) and testosterone was chemically synthesized by Butenandt and Hanisch (1935) and Ruzicka and Wettstein (1935).

Immediately after its chemical isolation and synthesis, testosterone was introduced into clinical medicine (unthinkable had it happened today) and used for the treatment of hypogonadism.