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Diethylstilbestrol Revisited: A Review of the Long-Term Health Effects

Ruthann M. Giusti, MD; Kumiko Iwamoto, MD; and Elizabeth E. Hatch, PhD
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From the National Cancer Institute, Bethesda, Maryland. Requests for Reprints: Ruthann M. Giusti, MD, Office of the Director, Division of Cancer Treatment, Building 31, Room 3A44, National Cancer Institute, Bethesda, MD 20892-2440. Acknowledgments: The authors thank Elizabeth Anderson, PhD; the National Institutes of Health DES Working Group (Florence Haseltine, MD; Suzanne Haynes, PhD; Robert Hoover, MD; Judith LaRosa, PhD; John McLachlan, PhD; Maria Merino, MD; G. Iris Obrams, MD, PhD; Iris Schneider; Susan Sieber, PhD; Kevin Tonat; Rosemary Torres, Esq; and Edward Trimble, MD); Paticia Hartge, ScD, for her helpful comments; and T. Timothy Chen, PhD, for statistical assistance.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;122(10):778-788. doi:10.7326/0003-4819-122-10-199505150-00008
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Purpose: To review the literature on the long-term health effects of exposure to diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES mothers), among their children exposed in utero to the drug (DES sons and daughters) and among the progeny of these exposed sons and daughters (DES grandchildren).

Data Sources: English-language articles were identified through MEDLINE and CANCERLIT searches and through review of the bibliographies of identified articles.

Study Selection: All human studies relevant to long-term health effects of exposure to DES were reviewed.

Data Extraction: Descriptive data on existing DES cohorts were extracted from early publications. Risk estimates for health effects were extracted from published reports.

Data Synthesis: An estimated 5 to 10 million Americans received DES during pregnancy or were exposed to the drug in utero. Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, <2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10 000. The association between DES exposure and testicular cancer in DES sons remains controversial. Exposure to DES has also been linked to reproductive tract abnormalities in DES sons and daughters that consist of immune system disorders and psychosexual effects. No evidence for transgenerational effects currently exists. Recommendations for screening persons exposed to DES are reviewed.

Conclusions: Further research is needed to define long-term health effects related to DES exposure. Such research would provide a basis for counseling persons exposed to DES and would further understanding of environmental and pharmacologic compounds similar to DES.


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Figure 1.
Relative risk estimates and 95% CIs for breast cancer among mothers exposed to diethylstilbestrol (DES) during pregnancy.

A relative risk greater than 1.0 indicates that DES increases the risk for breast cancer. The reference number for individual studies is given in parentheses.

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