Diethylstilbestrol

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Diethylstilbestrol (DES) is a potent synthetic estrogen. Between the late 1940s and the early

Figure 6.13 Comparison of the cumulative number of breast cancers expected among never-users of postmenopausal hormone therapy and women who had used it for durations of 5 and 10 years from age 50.

Estimated numbers for 1000 women based on breast cancer rates typical of Europe and North America. (Adapted from the Collaborative Group on Hormonal Factors in Breast Cancer.5)

Figure 6.13 Comparison of the cumulative number of breast cancers expected among never-users of postmenopausal hormone therapy and women who had used it for durations of 5 and 10 years from age 50.

Estimated numbers for 1000 women based on breast cancer rates typical of Europe and North America. (Adapted from the Collaborative Group on Hormonal Factors in Breast Cancer.5)

1960s, DES was widely prescribed to pregnant women in an attempt to reduce the risk of miscarriages, although by the early 1950s clinical trials had already shown that it was not effective for this purpose. Up to 2.5 million women in the United States alone may have used DES during pregnancy. By the early 1970s, several epidemiological studies had shown that DES caused an increased risk of clear cell adenocarcinomas of the vagina and cervix in women who had been exposed in utero, and DES use in pregnancy was banned in the United States in 1971, although use in Europe continued until 1978.19

Several randomized controlled trials and cohort studies have been analyzed to investigate whether women who used DES while pregnant have an increased risk of subsequently developing breast cancer. Overall, the results suggest that breast cancer risk is increased by about 30%.19-22 The total number of exposed cases studied is relatively small, and the details on doses are limited; therefore, it has not been pos sible to establish the relationships of risk with time since use of DES or dose.

The effect of DES on breast cancer risk is reasonably firmly established, but this exposure has several differences from exposures to other exogenous estrogens. For example, DES was given at high doses for a short period during pregnancy, whereas hormonal contraceptives and postmenopausal hormone therapy are given at low doses for a long period in nonpregnant women. The biological effects of DES may also differ from those of other exogenous estrogens because, in addition to its estrogenic effects, DES can have other effects, including causing sister chromatid exchange, unscheduled DNA synthesis, chromosomal aberration, disruption of the mitotic spindle, and aneuploidy.23

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