Tuesday, November 24, 2009

The history of testosterone

2005 marks the 100th anniversary of the creation of the term hormone by Ernest Starling. Although its biological effects were known since antiquity, the name testosterone (T) was coined only in 1935, when Ernest Laqueur isolated it from bull testes. The road to this isolation was long: John Hunter had transplanted testes into capons in 1786 and Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849. Following his observations, testicular preparations were used for therapy, popularised by self-experiments of Brown-Séquard (1889), which can at best have had placebo effects. Nevertheless, testis preparations were consumed until quite recently for the enhancement of virility. In the 1920s Sergio Voronoff transplanted testes from animals to men, but their effectiveness was disproven by the Royal Society of Medicine in 1927. Modern androgen therapy started when T was chemically synthesized independently in 1935 by Aldolf Butenandt and Leopold Ruzicka.

Since T was ineffective orally it was either compressed into subcutaneous pellets or was used orally as 17α-methyl T, now obsolete because of toxic side effects. In the 1950s longer-acting injectable T enanthate became the preferred therapeutic modality. In the 1950s and 1960s research concentrated on the chemical modification of androgens in order to emphasise their anabolic effects. Although anabolic steroids largely disappeared from clinical medicine, they continue an illegal life for doping. In the 1970s the orally effective T undecanoate was added to the spectrum of preparations. In 1992 WHO, NIH and FDA postulated preparations of natural T mimicking physiological serum levels, a demand first met by a transdermal scrotal film. Non-scrotal skin patches followed and finally in 2000 transdermal T gels became available. The most recent additions to T substitution therapy, the short-acting buccal T and the long-acting injectable T undecanoate, also fulfil the demand for physiological serum levels.

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