21514 Diethylstilbestrol

Pharmacology and toxicology

Diethylstilbestrol (DES) is a synthetic nonsteroidal estrogenic drug that was used therapeutically in the USA in the 1970s for threatened miscarriage and for maternal diabetes mellitus. The discovery of increased rates of vaginal clear-cell adenocarcinoma in adolescence among daughters whose mothers had received DES during pregnancy produced an international sensation (Herbst 1975). This drug provides the only proven example in human beings of prenatally-caused cancer (transplacental carcinogenesis). At least 25% of those young women who had prenatal exposure in the first trimester were born with vaginal, uterine, or fallopian tube anomalies. With male offspring, there appears to be an increased risk for ciyptorchidism, testicular hypoplasia, and abnormal semen cell morphology (Bibbo 1981).

Recently, the possibility of a transgenerational effect of DES has been under discussion. Some studies have found an increased risk of hypospadias in the sons of women exposed to DES irt utero (Pons 2005, Klip 2002), but the results of an ongoing study of DES-exposed persons, with data from 3916 exposed and 1746 unexposed women, do not support this potential transgenerational effect (Palmer 2005). Likewise, following intrauterine exposure to DES there have been three cases of newborns with limb-reduction defects reported, and two cases with deafness in the second generation after intrauterine exposure to DES (Stoll 2003). Several mechanisms could be involved in this possible transgenerational effect, such as a genotoxic effect of DES upon the germ cells, or imprinting, or genetic or epigenetic changes in the primordial oocytes, among others. Nevertheless, more studies should be conducted to confirm this potential effect.

Recommendation. Diethylstilbestrol use during pregnancy is contralndi-cated.

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