Family Matters

DES Daughters: Banned Pregnancy Drug Linked to Infertility, Prematurity and Cancer

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In the late 1960s, a cluster of teen girls and young women showed up at Massachusetts General Hospital and were diagnosed with a rare vaginal cancer, clear cell adenocarcinoma. It’s unusual even when it’s diagnosed in elderly women, but it was completely out of context in twentysomethings.

One woman, the mother of one of the affected girls, asked whether it could be connected to the drug she took in early pregnancy. That drug was DES, or diethylstilbestrol, which was widely prescribed in the U.S. beginning in 1940 to help stave off miscarriage — until 1971, when the U.S. Food and Drug Administration decided that the drug doesn’t work and that it causes cancer.

It also causes a host of other problems, many of which are detailed in research published this week in the New England Journal of Medicine. The study, from the National Cancer Institute (NCI), follows the daughters of women who took DES, the first synthetic form of estrogen, in pregnancy and gives the clearest picture to date of the health fall-out of the drug.

Researchers linked DES exposure to increased risks of 12 health conditions, including a twofold higher risk of infertility and a fivefold increased risk of having a preterm delivery. While the average woman has an 18% chance of delivering prematurely by the time she is 45, that figure jumps to 53% in DES-exposed daughters and 68% in those whose mothers took the highest dosages. DES-exposed daughters also face a greater risk of some cancers.

Compared with 15% of all women who struggle with infertility, DES-exposed daughters have a 33% chance of having reproductive problems. Those who do get pregnant have higher miscarriage rates throughout their pregnancy. “It’s kind of daunting,” says study author Bob Hoover, director of the epidemiology and biostatistics program at NCI.

MORE: The Risks (and Rewards) of Pills in Pregnancy

At the same time, the data also bolster concern over hormone exposure in utero and highlight the susceptibility of a growing fetus. “This has been a poster child for people who are concerned about hormone and endocrine disrupters in the environment like BPA,” says Hoover, referring to a controversial chemical in plastics. “This is an example of what can happen when you screw up a person’s hormonal balance in utero.”

In the study, researchers compared 1,900 unexposed women to 4,600 women whose mothers had taken the drug while they were pregnant, most in the early to mid-1950s when DES peaked in popularity. Up to 10 million pregnant women took the drug in the U.S.

Researchers asked the women about their medical and fertility history, collecting as much information as possible about various health-related outcomes in order to capture the full range of potential side effects.

In some cases, scary statistics wound up being reassuring. While researchers found that exposed women had a 40-times higher risk of developing clear cell adenocarcinoma, they point out that the low prevalence of the disease, in general, translates into a 1 in 1,000 risk.

The study also was able to quantify the actual possibility, or absolute risk, of exposed women developing other conditions:

  • First-trimester miscarriage: 50% chance for exposed women versus 37% for unexposed women
  • Loss of second-trimester pregnancy: 16% versus 2%
  • Stillbirth: 9% versus 3%
  • Neonatal death in the first month of life: 8% versus 0.6%
  • Ectopic pregnancy: 15% versus 3%
  • Preeclampsia:  26% versus 14%
  • Early menopause: 5% versus 2%
  • Pre-cancerous cervical changes: 7% versus 3%
  • Breast cancer: 4% versus 2%

Sons exposed to DES in utero weren’t studied, but previous research has not found decreased fertility.

MORE: Common Painkiller Use May Be Linked to Miscarriage Risk

Meanwhile, the DES-exposed daughters are all nearing the end of their child-bearing years. Researchers intend to keep following them to monitor the development of other potentially related conditions, such as heart disease or osteoporosis. They’re also keeping tabs on cancer risks and DES-exposed grandchildren, since genetic changes wrought by DES may be hereditary.

The most sobering takeaway from the study? DES didn’t work and may have even contributed to more miscarriages.

Bonnie Rochman is a reporter at TIME. Find her on Twitter at @brochman. You can also continue the discussion on TIME‘s Facebook page and on Twitter at @TIME.

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