Offspring of Women Exposed In Utero to Diethylstilbestrol (DES): A Preliminary Report of Benign and Malignant Pathology in the Third Generation.

Studies have shown a slightly increased risk of breast cancer in women who were given DES while they were pregnant. Their daughters, who were exposed to DES prenatally (before they were born), have an elevated risk of reproductive tract conditions, including a rare vaginal cancer. A question now being studied is whether DES health effects can be passed from the prenatally exposed women to their offspring (intergenerational transmission).

Studies in mice suggest that intergenerational transmission of DES health effects may be possible. Recent evidence indicates that prenatal exposure to DES may cause changes in the behavior of genes that influence hormones and the development of the female reproductive tract. These changes in gene behavior may be passed on to the next generation. Evidence for intergenerational transmission comes from mouse studies showing a higher number of reproductive tract tumors in the daughters of prenatally exposed female mice. We used the DES Follow-up Study data to assess whether cancer was more common in the offspring of women who were prenatally exposed to DES. Cancers affecting these offspring (the third generation) were identified using two approaches. First, we asked women participating in the DES Follow-up Study to report cancers diagnosed in their 8,216 third generation sons and daughters. Second, we asked 793 third generation daughters participating in the Third Generation Study to tell us about their cancers. We also asked the third generation daughters to tell us about their reproductive tract and breast biopsies. Next we confirmed the reported biopsies and cancers by checking the medical records of these third generation daughters.

Our results did not show an overall increase of cancer in the sons or in the daughters of prenatally DES-exposed women. However, based on only three cases, the number of ovarian cancers was higher than expected in the daughters of women exposed prenatally to DES. Because of the small number of cases, this result must be considered preliminary. The association may be a chance finding or may be due to the way in which the data were reported or collected. We did not find an association between DES and benign breast disease or reproductive tract conditions, but most of the women are too young for a meaningful assessment of these outcomes. Further follow-up is needed to assess whether prenatal DES exposure can affect the third generation in humans.

** PubMed abstract for this article **