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Since the early 1970s when the relationship of DES exposure in utero and clear-cell carcinoma of the vagina was established, parents and teenagers have feared the malignant potential these young women might carry. Although there is a high incidence of structural changes noted in the cervix and vagina of these girls, the vast majority of these changes are benign and do not appear to be malignant precursors. The "DES story" is not complete, but, in a short time, the epidemiology, pathogenesis, and. most importantly, its clinical management have evolved.
HISTORY
In the late 1940s and early 1950s, estrogen deficiency was thought by some to play a role in the high fetal death rate among pregnant diabetic women.1' Although not confirmed by other studies, DES was first used in diabetics and. soon thereafter, in patients who were threatening to miscarry, who had previous still births, and previous spontaneous abortions. Estrogens were used by some physicians through the late 1960s.
In 1970 Herbst and Scully reported seven carcinomas of the vagina in young women. Six of these tumors were dear-cell carcinoma. Carcinoma of the vagina is an extremely rare tumor occurring almost exclusively in the elderly, and clear-cell tumors are even more unusual.
On careful review, it was found that the mothers of these young women with clear-cell cancer had been heated with a synthetic estrogen, diethylstilbestrol (DES), at various stages of their pregnancies.B Subsequent investigation led to the discovery of the condition of vaginal adenosis in many young women exposed in utero to DES. It is estimated that 80 to 90 percent of patients exposed to intrauterine DES will show gross and microscopic evidence of vaginal and cervical adenosis. Initially, adenosis was considered premalignant and many therapeutic regimens were proposed. It is now felt by most authorities that adenosis coexists with the clearcell cancer rather than preceding the tumor.
SCOPE OF THE PROBLEM
It is estimated that two million women were treated with estrogens during their pregnancies. No relationship between malignancy and hormone supplementation has been found with the natural estrogens but only with DES derivatives. A clear-cell tumor registry has been established and, to dale, over 400 cases have been registered.9 The registry includes all clear-cell carcinomas of the female genital tract whether or not...