Prenatal DES exposure and increased occurrence of autoimmune disease

Can in utero exposure to DES adversely affect the immune system ?

1988 Study Abstract

Soon after recognition of the increased risk of vaginal clear cell adenocarcinoma in women with in utero exposure to diethylstilbestrol (DES), the National Cancer Institute funded a large multicenter epidemiologic cohort study, the DESAD Project. The purpose of this national project was to describe the prevalence of DES-associated genital tract changes among women exposed in utero and to compare these findings with an unexposed control group. Additionally, the study sought to determine the incidence of cancer and other diseases in the exposed and unexposed cohorts. Because of the possibility that prenatal exposure to DES might adversely affect the adult immune system, the participants in the DESAD Project were surveyed to determine the prevalence of autoimmune diseases. The lifetime history of these disease is reported in this preliminary communication.


As noted, research in rodents suggests that perinatal exposure to DES can markedly affect the adult rodent immune system,l whereas limited observations in humans raise the possibility of similar changes in the human immune system. The information presented in this preliminary communication also supports the concept that human exposure before birth to DES may subsequently affect the adult immune system. Unfortunately, no detailed serologic studies of the immune status of women exposed to DES in utero have yet been reported in the literature. Thus, it is not possible to identify any specific immune defect or an underlying mechanism for this association.

Although these data suggest that there is an increase in autoimmune disease among women exposed before birth to DES, the authors wish to caution against drawing firm conclusions from these preliminary findings. Although the overall occurrence of autoimmune disease is statistically significant with one-sided chi-square tests, the number of observed events is small, and the confidence intervals are wide. Additionally, the history of autoimmune disease has not yet been documented for all participants. At the present time, only one of the five centers has reviewed the medical histories to validate the questionnaire information. Twenty-four autoimmune diseases were reported by 23 women followed by the Mayo DESAD Center. Six women received all of their medical care outside of Mayo, leaving 18 evaluable cases. Of these 18 reported cases of autoimmune disease, 14 were confirmed. Two of the unconfirmed diseases occurred in an individual with longstanding psychiatric difficulties. Thus, there appeared to be only two cases in which a reliable participant reported a disease that could not be confirmed by examination of medical records.

Although the data reported here are necessarily indirect, they do indicate reason for concern. Consequently, it would seem prudent for investigators exposed women to determine the prevalence (and, it is hoped, incidence) of autoimmune diseases among their exposed cohorts. Additionally, studies should be undertaken to thoroughly investigate the function of the immune system in DES-exposed women by means of appropriate serologic testing.

  • Read and download the full study (free access) Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol, FERTILITY AND STERILITY, Vol. 49, No.6, June 1988.
  • Lifetime History of Autoimmune Diseases Among DES-Exposed Women (Record Review Cases) and Controls – image credit fertstert S0015-0282(16)59965-8.

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