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The History of DES

In 1938, researchers synthesized DES, the first manufactured estrogen (3). In the early 1940s, it became known that estrogen levels declined prior to pregnancy loss. Because of this, physicians began to recommend DES to pregnant patients who were at risk of miscarriage (12,13).

DES was never patented. Many companies manufactured and marketed DES, and it was sold under more than 200 different brand names. Advertisements aimed at influencing obstetricians promised that DES would not only prevent miscarriage and premature labor, but also make bigger, stronger babies.

In 1953, a randomized, controlled study showed that women prescribed DES did not have healthier pregnancies (2). However, marketing campaigns continued. No effective treatments to prevent early miscarriage were discovered. And, physicians continued to prescribe DES.

In 1971, physicians reported finding seven cases of a rare type of cancer, clear cell adenocarcinoma (CCA) of the vagina and cervix all in a group of young women whose mothers were prescribed DES, and all at a hospital that had never before had a case of this type of cancer (138). Subsequent studies showed that women whose mothers were prescribed DES during pregnancy had a 40 times greater risk of developing this typed of cancer than women in the general population (132). Based on this information, the FDA issued a drug bulletin contraindicating the use of DES during pregnancy (287). DES is no longer manufactured by pharmaceutical companies in the United States.

In the early 1970s, physicians began to systematically examine women and men whose mothers were prescribed DES while pregnant. They found an increased number of structural differences in this group compared to persons who had not been exposed to DES. One-third or more of women exposed to DES in utero (DES Daughters) have some identifiable genital abnormality (42,50,53). These include vaginal adenosis (Figure 8), (benign vaginal growths), cervical irregularities, including collars (Figure 6), hoods, septae, and cockscombs, (Figure 5) and abnormalities of the uterus (39,42,46,47,49,50,52,77,80,87,98,105,106,183). A "T-shaped" uterus (Figure 7) is commonly found (51,93). Men exposed to DES in utero (DES Sons) have an increased incidence of epididymal cysts, and may have an increased risk of other genital abnormalities as well. Studies exploring the relationship of in utero exposure to DES and testicular cancer have yielded mixed results (122,203,214,227,231). No conclusions about testicular cancer risks among DES Sons have been confirmed.

DES Daughters are more likely to be infertile than women who were not exposed to DES (101,108). Although most DES Daughters who become pregnant will carry a healthy baby to term, ectopic pregnancy, miscarriage, and premature birth are more common in DES Daughters (92). DES Sons, on the other hand, have not been found to have an increased risk of infertility (2,236).

Women prescribed DES while pregnant appear to have a modestly increased risk of breast cancer (21,24,25,33,117). No other health risks for them have been found.

No health risks have yet been confirmed for the children of DES Sons and Daughters. However, animal studies suggest that there might be an increased risk of cancer for them, as well. Animal and human studies are ongoing. For more information on ongoing studies, refer to DES Third Generation.

For a complete list of the numbered citations on this page see DES References.

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