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Study elucidates health risks for DES daughters

The synthetic estrogen diethylstilbestrol (DES) was widely prescribed in the 1940s, '50s, and '60s to prevent miscarriage and premature delivery. Its dangers were first revealed in the early 1970s, when Harvard-affiliated researchers linked the drug to a rare cancer of the vagina and cervix in the daughters of women who took DES while pregnant. In 1971, the FDA issued a warning against its use by pregnant women, but five to 10 million pregnant women and their babies had already been exposed. In the following decades, many other health problems were discovered among DES daughters. A report from the DES Follow-up Study, published in The New England Journal of Medicine (Oct. 6, 2011), documents the health risks for these women.

The study. In 1992, researchers contacted women who had participated in one of three studies of DES daughters undertaken in the 1970s. They recruited 4,653 women who had been exposed to DES in utero for a follow-up study, along with a control group of 1,927 women who had not been exposed. Using questionnaires, phone interviews, and medical records, the researchers assessed the cumulative risk for 12 health problems linked to DES exposure in earlier studies.

The results. The findings revealed a heightened risk for every one of the 12 conditions among the women exposed to DES (see table). For most of these conditions, DES exposure more than doubled the risk. The risk of ectopic pregnancy increased nearly fourfold, and the risk of preterm delivery increased nearly fivefold. In nine of the 12 conditions, the risk was highest among DES-exposed women who also had vaginal epithelial cell changes at a young age — suggesting exposure to high-dose DES early in gestation.

Rate of health problems among women* exposed vs. not exposed to DES in utero

Condition

Exposed
(% affected)

Not exposed (% affected)

Infertility

33

15.5

Miscarriage

50.3

38.6

Ectopic pregnancy

14.6

2.9

Pregnancy loss in second trimester

16.4

1.7

Preterm delivery

53.3

17.8

Preeclampsia

26.4

13.7

Stillbirth

8.9

2.6

Neonatal death

7.8

0.6

Early menopause

5.1

1.7

Precancerous cervical changes

6.9

3.4

Breast cancer (ages 40 and over)

3.9

2.2

Clear cell adenocarcinoma

0.1

0

*Women in the DES Follow-up Study

Limitations and implications. Except for cancer-related diagnoses, which were confirmed by medical records, data on health problems came mainly from the reports of participants. But the researchers noted several reasons to trust the women's recollections, including a greater than 90% rate of agreement between self-reports and medical records. These findings reinforce what clinicians have long recommended: if you're a DES daughter, you should have yearly gynecological exams, including a Pap test that samples the surfaces of the upper vagina in addition to the cervix. You should also have a mammogram done every one to two years, have yearly clinical breast exams, and practice breast self-exams. For more information about DES and cancer risk, go to www.cancer.gov/cancertopics/factsheet/Risk/DES.

Date Last Reviewed: 12/1/2011
Date Last Modified: 12/1/2011
Copyright Harvard Health Publications