Harvard Women's Health Watch

By the way, doctor: What are the health risks for DES daughters and their children?

Q. My mother took DES when she was pregnant with me. I'm now 69, my daughter is 41, and we've both had gynecological problems. What particular risks do we have because of our DES exposure, and what can we do about them?

A. DES, or diethylstilbestrol, is a synthetic estrogen that was prescribed in the 1940s, '50s, and '60s to prevent miscarriage and premature delivery. In 1971, the FDA issued a warning against its use in pregnant women after researchers at Massachusetts General Hospital in Boston linked it to a rare cancer of the vagina and cervix — clear cell adenocarcinoma (CCA) — in the daughters of women who took the drug while pregnant. Between 1938 and 1971, five to 10 million people in the United States were exposed to DES, including women who took the drug while pregnant (DES mothers) and the children born of these pregnancies (DES daughters and DES sons).

Many studies have confirmed links between DES exposure and various health risks. Most of these health problems also occur in people who haven't been exposed to the drug, and it's difficult to determine the cause in individual cases. But the research has identified health issues that people exposed to the drug should be on the watch for. Since 1992, the National Cancer Institute has been monitoring DES-exposed (and unexposed) mothers and their daughters and sons in a controlled investigation called the DES Follow-up Study (www.desfollowupstudy.org). The grandchildren of DES mothers have also been enrolled in a third-generation study. Here is what we've learned from this research about the health risks for DES-exposed women and men — and the precautions (if any) that they should take:

DES mothers (women prescribed DES while pregnant) have a modestly increased risk of breast cancer. The lifetime risk of breast cancer in a DES mother is one in six, while the lifetime risk of a woman who was not exposed to DES is one in eight. DES mothers should tell their clinicians about the exposure. They should have yearly clinical breast exams and regular mammograms (every one to two years), and they should practice self-breast exam.

DES daughters (women exposed prenatally to DES) have a 40-fold increased risk of CCA of the vagina and cervix, but even in this group, the disease is extremely rare — one case per 1,000 to 2,000 exposed daughters. DES daughters are 2.5 times more likely to develop breast cancer after age 40 than their unexposed counterparts. They don't appear to be more vulnerable than average to any other malignancy.

Prenatal DES exposure is also associated with several anatomical irregularities of the reproductive tract, including a T-shaped uterus, hooded cervix, abnormal vaginal tissue, and abnormalities of the fallopian tubes. Many of these irregularities are harmless, but they may contribute to pregnancy complications. Compared with women who were not exposed to the drug, DES daughters are at higher risk for ectopic (tubal) pregnancy, miscarriage, and preterm delivery. They also have a slightly increased risk of infertility.

Make sure your clinician knows you are a DES daughter. You should have yearly gynecological exams, including Pap testing that takes samples not only from the cervix but also from the surfaces of the upper vagina. You should continue Pap testing even after a hysterectomy. If your clinician detects any abnormalities during an exam, she or he may want to evaluate the vagina and cervix with colposcopy (inspection with a binocular-like magnifying device and biopsy of areas that look abnormal). You should also have yearly clinical breast exams and regular mammograms (every one to two years) and practice breast self-exam.

Selected resources

Centers for Disease Control and Prevention/DES Update
800-232-4636 (toll-free)

DES Action USA
800-337-9288 (toll-free)

DES Cancer Network
800-337-6384 (toll-free)

DES sons (men exposed prenatally to DES) have an increased risk of noncancerous epididymal cysts (growths on the testicles). A few studies suggest that they are also more likely to be born with undescended testes, a misplaced opening of the penis, or an abnormally small penis, but the findings have been inconsistent.

DES grandchildren (sons and daughters of women and men exposed prenatally to DES) do not appear to be at increased risk for DES-related health problems, but research is just beginning. There are no special screening recommendations. Nevertheless, the exposure should be noted in their health records. The CDC has compiled the latest information about DES in a booklet, DES Update, which you can download at www.health.harvard.edu/DES_update.

— Martha K. Richardson, M.D.
Advisory board member, Harvard Women's Health Watch