The 'DES Syndrome': a prototype of human teratogenesis and tumourigenesis by xenoestrogens?

Diethylstilboestrol (DES), the first synthetic hormone, when antenatally prescribed to prevent spontaneous abortion, has been described in the offspring to cause a variety of congenital abnormalities of the female genital tract. In addition, with an estimated absolute risk of 1:1000, it also causes clear cell adenocarcinoma (CCA) of the vagina and cervix in young ‘DES-daughters’. Also neuroteratogenic effects have been attributed to DES, but the psychopathology in DES-exposed persons is shown here to be largely iathrogenic, i.e. as a consequence of having been disproportionately alarmed by its potential toxicity. With over 20,000 publications, DES is one of the most studied compounds ever.
Yet, many doubts persist on its mechanisms of action, on whether or not it may have prevented some abortions, on the epidemiology and causation of CCA, and in how far it may have affected humans through the food-chain. Since no dose-effect relationship has been found in humans, it cannot be excluded that DES could have been toxic at low doses, and that other less potent xenoestrogens would have similar effects.

These questions are reviewed here, and new hypotheses on the mechanisms of action of DES and the epidemiology of CCA are presented. In the light of their recently discovered effects on developmental gene expression, DES and similar xenoestrogens are more appropriately to be called hormonal disrupters than modulators. However, the picture is far from clear. With so many doubts about the most extensively studied of oestrogens, a fortiori, the only firm conclusion that the DES story allows us to draw, with regard to other xenoestrogens, is that it is under the precautionary principle that their diffusion into the environment deserves to be prevented. It is recommended that this be done with due regard to the psychological consequences of excessive alarm.