Effects of Diethylstilbestrol (DES), a Trans-placental Carcinogen

Challenge

Diethylstilbestrol (DES) is the first carcinogen to have been shown to cross the placenta and cause cancer in the offspring. Between 1940 and the early 1970s millions of pregnant women were given DES, the first synthetic estrogen, in the mistaken belief that it would prevent complications of pregnancy. The earliest suggestion of a problem with DES was reported in a landmark publication in the NEJM that described a group of young women who had a rare vaginal cancer typically seen only in older women.

NCI researchers, led by Robert N. Hoover, M.D., Sc.D., developed the DES Follow-up Study in the mid-1990s, bringing together participants from four large clinical studies of DES-exposed and unexposed subjects conducted 20 years prior.

Advance

The DES Follow-up Study team located and re-contacted the women in the studies, and systematically followed them for long-term adverse health outcomes. In a landmark publication in the New England Journal of Medicine in late 2011, Dr. Hoover and his colleagues projected the burden of disease experienced by the millions women who were exposed in-utero. The authors report on 12 adverse health outcomes linked to DES exposure: infertility, spontaneous abortion, ectopic pregnancy, second trimester pregnancy loss, preeclampsia, preterm birth, stillbirth, neonatal death, natural menopause prior to age 45, cervical cancer, breast cancer after age 40, and clear-cell adenocarcinoma of the vagina and cervix.

Impact

Without the sustained follow-up of these women through the DES Follow-up Study, many of these outcomes would have been missed. The toll of the devastating health effects is unprecedented, particularly since DES was given to healthy individuals. This study has not only documented a public health disaster, but has served as the model for an entire area of research focused on the role of endocrine disruption in early life and subsequent health effects.