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Between 1947 and 1971, diethylstilbestrol (DES) was widely used in the United States for diabetic women during pregnancy and to treat threatened abortion. It is estimated that at least 2–3 million fetuses were exposed. A relationship between fetal DES exposure and clear cell carcinoma of the vagina was later discovered, and several other related anomalies have since been noted. In one-third of all exposed women, there are changes in the vagina (adenosis, septa), cervix (deformities and hypoplasia of the vaginal portion of the cervix), or uterus (T-shaped cavity) (eFigure 18–19).

eFigure 18–19.

Cervical changes in women exposed to diethylstilbestrol (DES) in utero. A: Circular sulcus. B: Central depression and ectopy (covered by columnar epithelium.) C: Portio vaginalis and ectopy. D: Anterior cervical protuberance (rough). E: Anterior cervical protuberance (smooth). (Reproduced, with permission, from DeCherney AH, Nathan L, Laufer N, Roman S. Current Diagnosis & Treatment: Obstetrics & Gynecology, 12th edition. McGraw-Hill, 2019.)

All women known to be exposed prenatally are advised to have an initial colposcopic examination to outline vaginal and cervical areas of abnormal epithelium, followed by cytologic examination of the vagina (all four quadrants of the upper half of the vagina) and cervix at yearly intervals. Lugol iodine stain of the vagina and cervix will also outline areas of metaplastic squamous epithelium.

Many women are not aware of having been exposed to DES. Therefore, in the age groups at risk (50–74 years), examiners should pay attention to structural changes of the vagina and cervix that may signal the possibility of DES exposure and indicate the need for follow-up.

The incidence of clear cell carcinoma is approximately 1 in 1000 exposed women, and the incidence of cervical and vaginal intraepithelial neoplasia (dysplasia and carcinoma in situ) is twice as high as in unexposed women. DES daughters have more difficulty conceiving and have an increased incidence of early abortion, ectopic pregnancy, and premature births. In addition, mothers treated with DES in pregnancy appear to have a small increase in the incidence of breast cancer, beginning 20 years after exposure.

WHEN TO REFER

All patients with a history of DES exposure should be monitored by an experienced colposcopist.

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Wautier  A  et al. Genital tract and reproductive characteristics in daughters of women and men prenatally exposed to diethylstilbestrol (DES). Therapie. 2020;75:439.
[PubMed: 31806244]  

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