Epidemiological studies of the effects of diethylstilboestrol.

Herbst and his colleagues first showed in 1971 that girls born to mothers who had taken diethylstilboestrol (DES) during pregnancy were at an increased risk of clear-cell adenocarcinoma of the vagina and cervix. At first it was feared that these girls would have a high probability of developing clear-cell carcinomas, but the latest report from the Registry for Research on Hormonal Transplacental Carcinogenesis of the University of Chicago puts the risk at only 1 per 1000 of those exposed, from birth through to age 34. On this basis, Herbst and his colleagues have suggested that DES is not a complete carcinogen, but that some other factor is involved in the pathogenesis of clear-cell carcinoma of the vagina and cervix. Women exposed in utero to DES have a high prevalence of vaginal adenosis and tend, therefore, to have an extensive transformation zone on the cervix and in the vagina. There is considerable controversy as to whether or not such women are at increased risk for vaginal and cervical intraepithelial neoplasia. The latest findings from the Study of the Incidence and Natural History of Genital Tract Anomalies and Cancer in Offspring Exposed in Utero to Synthetic Estrogens (the DESAD project) are, however, worrying; during follow-up, vaginal and cervical intraepithelial neoplasia occurred at a rate of 15.7/1000 woman-years in the exposed and at a rate of 7.9/1000 woman-years in the controls (p = 0.01). There is some evidence that exposure in utero to exogenous oestrogens increases the risk of testicular cancer in males. The findings, however, are not conclusive, and the effect does not seem to be specific to DES and related nonsteroidal oestrogens.