On the Teratogenic Action of Diethylstilbestrol and Other Exogenous Sexual Hormones

Abstract

The synthetic estrogen diethylstilbestrol used between 1948 and 1970, mainly in the United States, as an antiabortive agent was found to be the cause for the appearance of vaginal clear-cell adenocarcinoma in around 350 young women born to mothers who were treated with this product during pregnancy because of the threat of abortion. The discovery of this etiologic relationship was made by a group of gynecologists and pathologists in Boston after seeing a clustering of the first eight cases within 3 years (Herbst et al. 1971). The pathogenetic mechanism of this cancer in women prenatally exposed to DES has since been understood by toxicologists as a transplacental cancerogenesis — the only one found as far in the human being.

This theory is discussed in view of the fact that cancer developed only in a very low percentage of such prenatally exposed young women while a large majority presented with a benign teratogenic change: vaginal adenosis. To the pathologist the dysplastic transformation of glands of this atypical vaginal mucosa into adenocarcinoma in the pubertal woman suggests itself as a more likely pathogenesis. Thanks to the continuous investigation this hypothesis has now obtained strong support by casuistic material with evidence of such direct transformation.

Apart from the masculinizing effects found in daughters of women treated with progestins against premature delivery or abortion, DES thus is the only sexual hormonelike synthetic drug with a proven teratogenicity. All other sexual steroids used in contraception, pregnancy tests and so-called protective treatment have not as yet provided clear cut evidence for a teratogenic action.