PEDIATRICS Vol. 62 No. 6 December 1978, pp. 1151-1159
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Complications of Prenatal Therapy With Diethyistilbestrol

Arthur L. Herbst M.D.1, Robert E. Scully M.D.1, Stanley J. Robboy M.D.1, and William R. Welch M.D.1

1 Department of Obstetrics and Gynecology, University of Chicago, Pritzker School of Medicine, and the Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston

Cancer of the vagina is a rare type of genital malignancy that usually occurs as squamous cell carcinoma in postmenopausal women. Vaginal clear cell adenocarcinoma (Fig. 1), which used to be termed "mesonephroma," is an extremely rare type of genital cancer and was almost never encountered in younger patients until recently. In 1970, a clinical and pathologic study of seven cases of clear cell adenocarcinoma of the vagina in females between the ages of 14 and 22 years was published; all of them had been seen or treated in the late 1960s. These seven cases exceeded the total number of this type of cancer that had been previously reported in this age group.1 The next year, a retrospective epidemiologic study was conducted that included an additional case, and this cohort of eight was compared to 32 controls. It was found that the risk of development of these carcinomas was significantly associated with intrauterine exposure to diethylstilbestrol.2

Diethylstilbestrol therapy for high-risk pregnancy to reduce fetal wastage had been very popular in the late 1940s and 1950s. However, its use was stated to be contraindicated in 1971 by the Food and Drug Administration after the results of the initial epidemiological studies were confirmed.3 Clear cell adenocarcinoma of the cervix has also been associated with intrauterine exposure to diethylstilbestrol.4,5 In addition, other similar nonsteroidal synthetic estrogens such as dienestrol and hexestrol have also been implicated in the association.

Studies of the clinical, epidemiological, and pathologic aspects of these neoplasms have been centralized in the Registry for Research on Hormonal Transplacental Carcinogenesis (formerly the Registry of Clear Cell Adenocarcinoma of the Genital Tract in Young Females).