Isolation of gonadal androgens
The use of gonadal steroids pre-dates their identification and isolation. Medical use of testicle extract began in the late 19th century while its effects on strength were still being studied. The isolation of gonadal steroids can be traced back to 1931, when Adolf Butenandt, a chemist in Marburg, purified 15 milligrams of the male hormone androstenone from tens of thousands of litres of urine. This steroid was subsequently synthesized in 1934 by Leopold Ruzicka, a chemist in Zurich.
In the 1930s, it was already known that the testes contain a more powerful androgen than androstenone, and three groups of scientists, funded by competing pharmaceutical companies in the Netherlands, Germany, and Switzerland, raced to isolate it. This hormone was first identified by Karoly Gyula David, E. Dingemanse, J. Freud and Ernst Laqueur in a May 1935 paper “On Crystalline Male Hormone from Testicles (Testosterone).” They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The chemical synthesis of testosterone was achieved in August that year, when Butenandt and G. Hanisch published a paper describing “A Method for Preparing Testosterone from Cholesterol.” Only a week later, the third group, Ruzicka and A. Wettstein, announced a patent application in a paper “On the Artificial Preparation of the Testicular Hormone Testosterone (Androsten-3-one-17-ol).” Ruzicka and Butenandt were offered the 1939 Nobel Prize in Chemistry for their work, but the Nazi government forced Butenandt to decline the honor, although he accepted the prize after the end of World War II.
Clinical trials on humans, involving either oral doses of methyltestosterone or injections of testosterone propionate, began as early as 1937. Testosterone propionate is mentioned in a letter to the editor of Strength and Health magazine in 1938; this is the earliest known reference to an AAS in a U.S. weightlifting or bodybuilding magazine.
Development of synthetic AAS
The development of muscle-building properties of testosterone was pursued in the 1940s, in the Soviet Union and in Eastern Bloc countries such as East Germany, where steroid programs were used to enhance the performance of Olympic and other amateur weight lifters. In response to the success of Russian weightlifters, the U.S. Olympic Team physician John Ziegler worked with synthetic chemists to develop an AAS with reduced androgenic effects. Ziegler’s work resulted in the production of methandrostenolone, which Ciba Pharmaceuticals marketed as Dianabol. The new steroid was approved for use in the U.S. by the Food and Drug Administration (FDA) in 1958. It was most commonly administered to burn victims and the elderly. The drug’s off-label users were mostly bodybuilders and weight lifters.