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Frobenius W  
"The Rabbits are Prepared ..." - The Development of Ethinylestradiol and Ethinyltestosterone

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2011; 8 (Sonderheft 1): 32-57

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Keywords: contraceptionendocrinologyEthinylestradiolethisteronehistorysteroids

In an exciting scientific neck-and-neck race, European and American scientists in the late 1920s and early 1930s isolated the ovarian, placental, and testicular hormones. At the same time the constitution of the human sex steroids was elucidated. However, it soon emerged that with oral administration the therapeutic value of the natural substances was extremely limited. The first-pass effect in the estrogens, the sensitivity of progesterone to gastric acid, and the short plasma half-lives of natural ovarian hormones made treatment with them largely ineffective. The development by Hans Herloff Inhoffen and Walter Hohlweg of the orally effective sex steroids ethinylestradiol and ethinyltestosterone (ethisterone) in Berlin in 1937 can therefore be regarded as a milestone in the history of gynecological endocrinology. Ethinylestradiol is found even today as a highly effective estrogen component in almost all combined oral contraceptives. Ethinyltestosterone was the very first synthetic gestagen and can be regarded as the progenitor of the modern steroids in the 19-nortestosterone series. The present study describes details of the development of these two steroids and the history of their reception in the field of gynecology. In addition to the scientific literature, previously unexamined archival materials and German and American patent specifications were used in the study. The results show several surprising aspects, which are discussed in detail.
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