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 testic-ular preparations for therapeutic purposes. The best known experiments are those by Brown-Sequard (1889), who tried testis extracts on himself which can at best have had placebo effects (Cussons etal. 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 byLoewe 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 etal. (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. Since testosterone was ineffective orally it was either compressed into pellets and applied subcutaneously or was used in the form of 17a-methyltestosterone. In the 1950s longer-acting injectable testosterone esters (Junkmann 1957) became the preferred therapeutic modality. In the 1950s and 1960s chemists and pharmacologists concentrated on the chemical modification of androgens in order to emphasize their erythropoetic (Gardner and Besa 1983) or anabolic effects (Kopera 1985). These preparations never played an important role in the treatment of hypogonadism and were abandoned for purposes of clinical medicine. In the late 1970s the orally effective testosterone undecanoate was added to the spectrum of testosterone preparations used clinically (Coert et al. 1975; Nieschlag et al. 1975). In the mid 1990s, transdermal testosterone patches applied either to scrotal skin (Bals-Pratsch etal. 1986) or non-scrotal skin (Mazer et al. 1992) were introduced into clinical practice. In 2000, a transdermal testosterone gel became available for treatment of male hypogonadism, first in the US and subsequently in other countries as well (Wang etal. 2000).

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Hair Loss Prevention

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