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

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.