Diethylstilbestrol (DES)

Various theories to account for the effects of DES have been presented. What is clear is that the diseases associated with DES derive from structural damage of the fetus caused by the drug. The drug is most damaging when taken early in pregnancy, when the reproductive organs are formed. (Researchers have found that daughters of mothers who took DES in their eighteenth week of pregnancy or later had fewer abnormalities.) One explanation suggests that DES exposure causes abnormal development of the Mullerian ducts, paired structures present in the early embryo. During a normal pregnancy, the Mullerian ducts form the female reproductive tract, including the uterus, the fallopian tubes, the vagina, and the cervix. DES causes the persistence of a type of glandular, or secreting, epithelial cell in the vagina. During normal development, this type of cell is transformed to a squamous, or flattened, cell. The persistence of this type of cell, researchers speculate, could make affected women more susceptible to a cancer-promoting factor. They have also suggested that vaginal cancer does not develop until after menstruation begins because this susceptible tissue reacts to estrogens released naturally in women who menstruate.

To explain the higher rate of premature deliveries and infertility in DES daughters, scientists point to the abnormal development of the cervix or endometrium in the embryo. Another possible explanation is that DES somehow causes defects in the connective tissue of the fetal cervix and uterus, so that these organs cannot develop normally.

There is also a possibility that the abnormal cells in the vagina and cervix of DES daughters will become malignant later in life. While this is unusual, physicians are advised to examine DES daughters regularly to monitor their condition. Arthur L. Herbst reports that only 16 of the hundreds of thousands of DES daughters who have been examined have had tumors develop from vaginal adenosis or a related condition of the cervix, cervical ectropion.

Predictions that the number of DES daughters with cancer would continue to grow dramatically have fortunately proven false. But researchers warn that DES daughters, sons, and mothers may face other health complications as they get older. The legacy of DES has been long-lasting and troubling, a reminder of the power of medicine to hurt as well as help.