The Synthetic Estrogen Stilbestrol: an Experimental and Clinical Evaluation

DES experimented while missing test controls – tested without properly designed trials

1941 Article Abstract

The natural estrogens have proved their value in the treatment of the severe menopausal syndrome, vaginitis of children and senile women, and certain types of amenorrhea, migraine and abnormal breast hyperplasia. Two principal drawbacks attend the clinical use of the natural estrogens—the high cost, especially when large doses are required, and the loss of potency when administered orally. The advantage of the oral administration of endocrine products in the attempt to overcome a relative or actual deficiency is apparent when one recollects that the various hormones are normally produced in minute quantities at a relatively steady rate. This process cannot be imitated by hypodermic injections at intervals of two or three days.

For these and other less important reasons, the need of an orally potent, synthetic estrogen is constantly engaging the attention of the biochemist and the clinician. When Dodds and his associates1 announced in 1938 the synthesis of the highly active estrogen stilbestrol, the product was welcomed for clinical trials with guarded hopefulness throughout the world. … …

… … In the investigation of stilbestrol herein reported, we set out to determine :

  1. The comparative potency of the product in the animal in terms of the international unit of estrone

  2. Its rate of absorption and excretion in the human being

  3. Its therapeutic effectiveness as gaged by its ability to produce growth of the endometrium and withdrawal bleeding in castrated, menopausal and amenorrheic women; and by its relative effectiveness in relieving the carious conditions wherein the natural estrogens are successfully employed.

  4. The incidence of toxic symptoms in the human being

  5. The possibility of tissue damage in the human being

  6. Its damaging effects on the vital organs of animals



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