In 1938 Dodds, Goldberg, Lawson and Robinson1 announced the synthesis of a new estrogenic agent, diethylstilbestrol (4: 4-dihydroxy-alpha: beta-diethyl stilbene). As can be seen from its formula, it does not contain the phenanthrene ring system formerly thought to be necessary for estrogenic activity. It was found an extremely powerful estrogenic agent in animals, suffering little diminution in potency by the oral as compared to the parenteral route.2 It reproduced the effects of the natural estrogens in animals and was about two and one-half times as active as estrone by injection. By the oral route the superiority over the natural estrogen was far greater, since the naturally occurring compounds lose a high percentage of their activity when given by mouth. In man the loss of activity of the natural estrogens given by mouth has been shown to be as much as 95 per cent, as judged by vaginal smears.
SHORR E, ROBINSON FH, PAPANICOLAOU GN. A CLINICAL STUDY OF THE SYNTHETIC ESTROGEN STILBESTROL. JAMA. 1939;113(26):2312–2318. doi:https://doi.org/10.1001/jama.1939.72800510003010
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