Pregnant mums taking miscarriage prevention drug decades ago may have put their girls at risk of infertility and cancers

By Dr. Ananya Mandal, MDOct 6 2011

A new study reveals that a drug that was taken by millions of pregnant women decades ago to prevent miscarriage and complications has put their daughters at higher risk for breast cancer and other health problems. The study shows that many of these daughters are now over 40 and may not even know of their risk if their mothers never realized or told them they had used the drug, a synthetic estrogen called DES or Diethyl stilbesterol.

The new study suggests that infertility is twice as common and that breast cancer risk is nearly doubled in these daughters. The sons of DES users also face health risks - testicular problems and cysts - but these are less well studied and don't seem to be as common. Even less is known about the third generation – “DES grandchildren” say researchers. Some research suggests these girls start menstruating late and have irregular periods, possible signs of fertility issues down the road.

In the United States alone, more than 2 million women and 2 million men are thought to have been exposed to DES while in the womb and may now want to talk with their doctors about when they should be screened for health problems. “We don't want to cause a panic of everyone rushing out thinking they're going to get cervical or breast cancer. They just need to have that conversation with their physician,” said Dr. Sharmila Makhija, women's health chief at the University of Louisville.

The average woman has about a 1 in 50 chance of developing breast cancer by age 55; for DES daughters it's 1 in 25, the study found. Risks for other health problems vary. DES was widely used in the United States, Europe and elsewhere from the 1940s through the 1960s to prevent miscarriage, premature birth, bleeding and other problems. Many companies made and sold it as pills, creams and other forms. Studies later showed it didn't work. The government told doctors to stop using it in pregnancy in 1971, after DES daughters in their late teens and 20s were found to be at higher risk of a rare form of vaginal cancer. Further research has tied DES to infertility and various pregnancy problems.

“They've been identified one at a time. Nobody's been able to get the whole picture,” said Dr. Robert Hoover, a researcher at the National Cancer Institute. The new study, which he led, “takes the woman and looks at everything that can happen as a result of this drug,” and adds evidence for some previously suspected risks like breast cancer, he said. Results are published in Thursday's New England Journal of Medicine.

The study started in 1992 and involved about 4,600 DES daughters and a comparison group of 1,900 similar women whose mothers had not used DES. Their health was tracked over time through surveys and medical records. Their average age at the last follow up was 48.

Results showed that breast cancer risk was 3.9 percent versus 2.2 percent among the DES exposed and non exposed respectively. Cervical pre-cancer risk was 6.9 percent versus 3.4 percent, infertility risk was 33.3 percent versus 15.5 percent, early menopause risk was 5.1 percent versus 1.7 percent. Among pregnant women complications like preterm delivery was 53.3 percent among exposed versus 17.8 percent among non exposed. Miscarriage incidence was 50.3 percent versus 38.6 percent, tubal pregnancy 14.6 percent versus 2.9 percent, stillbirth 8.9 percent versus 2.6 percent and preeclampsia (high blood pressure during pregnancy), 26.4 percent versus 13.7 percent.

DES exposure needs to be considered with the whole picture of a woman's risk, said Dr. G. Wright Bates, director of reproductive medicine at the University of Alabama at Birmingham. “In some cases, frequent Pap smears and early mammography or breast MRI may be warranted for women with DES exposure,” he said.

What many other researchers are worried about is the effect on the third generation. “There is certainly laboratory animal evidence of third-generation effects,” Hoover said. “So we have been trying to put together enough granddaughters to study them as well. Thus far, we do not have enough data to say much.”