Long-term Effects of Exposure to Diethylstilbestrol
1988 Study Abstract
The present survey represents a preliminary look at possible health effects of prenatal exposure to DES in humans beyond those already known. As such, it should be considered as a guide to areas needing further investigation in less biased samples. The findings, however, are consistent with those of experimental studies in animals and indicate a need for follow-up in the human cohort. Of particular note are conditions that suggest impaired immune function, such as infectious illness, allergic and autoimmune conditions, and malignant tumors.
Studies of certain genetic strains of mice with exposure to DES during the critical neonatal period of immune system ontogeny-analogous to the first trimester of human pregnancy-show persistent, lifelong immunosuppression. The main DES effect is a reduced number of Thelper cells, important for the induction and regulation of many immune responses. B-cell response is impaired in assays requiring T-cell mediation but is normal if corrected for T-helper numbers. Experiments with varying combinations of B and T cells in vitro show that the defect is in T-cell number but not function.
Mice with neonatal exposure also have a reduced number of natural killer cells thought to recognize and kill certain tumor cells. Following injection with a classic carcinogen (3-methylcholanthrene [MCA]), DES-exposed mice show a reduced ability to resist tumors; MCA-induced sarcomas appear in greater numbers and at a faster rate.
Our findings regarding asthma, arthritis, and lupus are also consistent with those of a small study of human peripheral blood lymphocytes suggesting a hyperreactive immune response in women with in utero exposure to DES. Another small study of the daughters suggested possible functional alterations of natural killer cells. Even more suggestive, our findings are consistent with those of a recent preliminary report from the largest ongoing follow-up of DES daughters, the federally funded Diethylstilbestrol Adenosis Project. This report indicates about a twofold increase in autoimmune conditions in women with prenatal exposure compared with controls. One small study of daughters who had had DES associated cancer or reproductive problems showed no consistent increase in the rates of infectious disease but a suggestive increase in the rates of autoimmune disease compared with controls.
Evaluating immunologic consequences in women and men with DES exposure will be complicated by possible genetic contributions and by varying dosage and timing of the prenatal exposure. Furthermore, health consequences might become detectable only as the population ages, when the immune system generally declines in competence.
Possible pathologic disorders of the prostate, as noted in our survey, were also noted in experimental models of DES effects in rodents.In preliminary studies of mice with neonatal DES exposure, evidence of cytologic malignancy in the area of the prostate appeared only in the experimentally treated animals. Recent experiments in which human fetal prostate tissue was grafted into DES-treated and untreated athymic nude mice and then allowed to continue growing revealed ductal dilation and persistent distortion of ductal architecture; these conditions could contribute to early or increased development of prostatic neoplasms (S. Mee, G.R. Cunha, C.V. Yonemura, et al, “The Effects of Diethylstilbestrol on Human Prostate Development,” unpublished data, 1987).
Further inquiry should also focus on a possible increased prevalence of elevated prolactin levels among DES daughters. Substantial endocrine alterations occur in rodents; more specifically, experimental studies show that perinatal DES exposure results in a disruption of hypothalamic-pituitary feedback systems, including the regulation and production of prolactin. While endocrine effects of a similar magnitude are not apparent within the human cohort, there could be an increase of more subtle functional alterations in daughters or sons (or both) with exposure to DES. Although difficult to measure, abnormal endocrine function could be contributing to a diminished reproductive capacity in ways beyond the more apparent and well-documented structural anomalies. Two small studies of plasma hormones in the daughters suggest abnormalities that may reflect a disturbance of hypothalamic-pituitary-ovarian function. An additional study suggests that hyperprolactinemia may be a significant factor in infertility in daughters with DES exposure.
Comprehensive follow-up of DES-exposed daughters and sons is required to answer questions about the long-term consequences of prenatal exposure. As the cohort ages and reaches new “milestones” of increased health risks, such follow-up can contribute to a more adequate assessment of this population’s risks and to the early detection of various health conditions that may be affected by prenatal DES exposure and be responsive to treatment. In addition, an increased knowledge of the health consequences associatedwith DES exposure addresses a broader scientific need to examine fully the results of this reproductive exposure. Women and men with in utero exposure to DES constitute a unique, identified cohort from which much can be learned about the hormonal effects on both normal and abnormal human development. This cohort can provide a greater understanding of developmental biology, sex differentiation, and pathologic processes in humans. Beyond the basic knowledge to be gained are implications for therapeutic substances in use currently or considered for the future.
Sources and more information
- Full study (free download) : Long-term Effects of Exposure to Diethylstilbestrol, Clinical Medicine, NCBI PubMed PMC1026532, 1988 Nov.
- Prevalence Rates (%) of Selected Conditions Among Adults With Diethylstilbestrol (DES) Exposure featured image credit ncbi.
DES DIETHYLSTILBESTROL RESOURCES
- Source DES and autoimmune disease, immune-related diseases studies.
- Diethylstilbestrol DES studies by topics.