Most people can’t even pronounce diet hylstilbestrol, let alone recall the drug’s legacy.
Yet for more than three decades, doctors routinely prescribed diethylstilbestrol di-ETH-il-stil-BES-trol, or DES to millions of U.S. women to prevent miscarriages. They finally stopped in 1971, when scientists first recognized that DES could harm daughters born to women who took it while pregnant.
Although more than 30 years have passed since a U.S. obstetrician prescribed the synthetic estrogen, DES continues to plague those who took it and their children, many of whom have no idea they were exposed.
For the most part, babies whose mothers took DES reached their teens or young adulthood before problems arose. Even then, their ”birth defects,” such as an increased risk of cancer or a misshapen uterus, weren’t apparent to the casual observer.
That is one reason why, in 2003, the Centers for Disease Control and Prevention has launched an educational campaign about DES. The campaign, targeting lay people as well as doctors, features a Web site www.cdc.gov/DES with the latest information about the drug’s lingering effects.
”It’s a linguistic challenge,” says DES daughter Margaret Braun, author of DES Stories (Visual Studies Workshop Press, 2001). ”We say DES was, and we forget that we’re talking about a toxic chemical exposure with a lag time before the injuries may surface.”
DES activists speculate that half of those exposed to the drug, while pregnant or in the womb, don’t realize they were. The drug went by scores of brand names, and some pregnant women assumed that the pills were prenatal vitamins.
Many who do know they were exposed, as well as many of their doctors, activists say, mistakenly think they are past the age when DES could hurt them.
In reality, ”it’s not going to go away until we all die,” says DES daughter Susan Helmrich, 47, co-founder of the DES Cancer Network with Braun.
As growing numbers of DES daughters reach the age when breast cancer and other hormonal-related malignancies generally become more common, scientists wonder whether they’ll see an upswing in cases.
And preliminary research found an elevated rate of a benign genital defect in sons of DES daughters. That finding, coupled with a higher rate of tumors in offspring of mice exposed to DES in the womb, raises concerns that problems caused by the drug might not go away even after everyone who was directly exposed has died.
Helmrich was only 21 and had just graduated from college when she was diagnosed with a rare cancer called clear cell adenocarcinoma, a hallmark of DES exposure in the womb.
”I was an athlete in college,” says Helmrich, of Berkeley, Calif. ”I looked healthy. I looked fine.” Doctors removed the cancer and surrounding tissue in a 10-hour operation.
Helmrich’s mother, now 76, was diagnosed with breast cancer at age 39, years before researchers began noticing that DES mothers have a higher breast cancer risk than other women.
Four years ago, Helmrich, who never smoked, learned she had lung cancer. Scientists don’t think DES is linked to lung cancer, says Helmrich, a Ph.D. epidemiologist, but she does.
”My life has been completely affected, altered, influenced, changed by my DES exposure,” she says. ”Every single thing in my adult life: the way I live, the way I eat, the way I worry.”
DES daughter Susan Wood, 44, says she doesn’t think about the drug every day. ”But I do miss my sister every day,” says Wood, the middle of three siblings who were all exposed to DES in the womb.
Wood’s older sister, Betsy, died at age 34 of clear cell adenocarcinoma. Her younger brother was diagnosed with testicular cancer at 23 but is now cancer-free.
Wood, who has had reproductive problems, directs the Food and Drug Administration’s Office of Women’s Health. DES did not drive her decision to become a scientist, but ”it adds to my perspective on what I do in women’s health.”
Wood and Helmrich were adolescents when U.S. doctors finally stopped prescribing DES to pregnant women. The drug received a one-two punch in 1971:
* In April, researchers reported in The New England Journal of Medicine on eight cases of clear cell adenocarcinoma in women decades younger than when it usually is diagnosed. In every case but one, their mothers had taken DES while pregnant. That November, the FDA issued a bulletin telling doctors to stop treating pregnant women with the drug.
Robert Hoover, a National Cancer Institute medical epidemiologist who studies the drug’s effects in people, says the odds of a DES daughter developing clear cell adenocarcinoma appear to be one-in-1,000 to one-in-1,500.
Nora Cody, executive director of DES Action, a non-profit consumer group based in Oakland, says many doctors are misinformed about the disease. ”They think that the cancer risk goes away when you turn 30 or 35,” Cody says.
But it doesn’t. University of Chicago obstetrician/gynecologist Arthur Herbst, lead author of the first paper to link DES exposure to the rare vaginal cancer, maintains a registry of women diagnosed with the disease. Of the registry’s nearly 800 women from around the world, Herbst says, the oldest were in their early 50s when diagnosed.
Infertility problems more likely
Though the vast majority of DES daughters will not develop cancer, many have experienced reproductive problems. In one study, DES daughters were 80% more likely than unexposed women to have failed to conceive after at least a year of trying. The same study, published in 2001, found that DES daughters’ infertility problems were mainly a result of uterine and tubal problems.
Activists complain that despite such findings, infertility specialists, like most OB-GYNs, neglect to ask patients whether their mother took DES while pregnant.
That information can make a big difference in treatment, says Boston University epidemiologist Julie Palmer, lead author of the aforementioned study. ”When I get calls from women about this, I always recommend that they find a physician who’s really familiar with DES,” Palmer says.
One of the great ironies of DES is that doctors prescribed it to help patients avoid miscarriages and deliver bigger, stronger babies. Yet there was never any solid evidence to support its effectiveness.
Michael Freilick’s mother took DES while pregnant with him, but he was six weeks premature and weighed only 4 pounds. Freilick had never heard of DES until he was diagnosed with testicular cancer at age 30. Up to then, he says, his mother ”just didn’t think there was a need to tell me.”
Scientists may never know whether DES is linked to testicular cancer. ”It certainly has not been demonstrated that it is related to testicular cancer risk, but it hasn’t been ruled out,” Hoover says. ”The dilemma there is, we may not get more information on that by continuing to follow men up.”
The reason: Unlike most malignancies that strike in adulthood, the risk of testicular cancer peaks in the 20s and then drops steeply in the 30s, Hoover says. So DES sons are past the age when they’re most likely to develop the disease.
Trusting in science
Freilick, a salesman in Cherry Hill, N.J., understands this, but he still has no doubts that the DES his mother took led to his testicular cancer. Now 49, Freilick was just diagnosed with bladder cancer, unusual in a non-smoker like himself but not thought to be linked to DES exposure. And he wonders whether scientists will see an increased risk of prostate cancer in DES sons now that they are aging.
DES’ popularity soared along with the post-World War II baby boom. In a 1949 New England Journal of Medicine article, two Harvard Medical School OB-GYNs extolled the drug’s use in preventing miscarriages.
Just four years later, William Dieckmann of the University of Chicago published contrary findings in the American Journal of Obstetrics & Gynecology.
Dieckmann compared 800 women who had taken DES while pregnant with 800 who took a placebo. The DES group had just as many miscarriages and preemies as the placebo group. In other words, the drug didn’t work. (A later analysis of his work found that women on DES actually were less likely to deliver a full-term baby than those on the placebo.)
No matter. Thanks to aggressive marketing, the drug was more popular than ever. U.S. doctors prescribed DES to an estimated 5 million pregnant women.
Pat Cody, 79, took DES while pregnant with her first daughter, born in 1956. Cody, founder of DES Action, says she and her husband willingly paid $30 a month for the drug. At the time, Cody says, they were paying only $75 a month to rent their cottage in Palo Alto, Calif.
Her younger daughter, Nora, 41, was lucky. Cody switched OB-GYNs, and her new doctor was not one of the DES faithful.
Cody’s firstborn had an ectopic pregnancy, in which the embryo lodged in a fallopian tube. She then developed severe endometriosis, leading to a hysterectomy at age 34. Nora Cody says her family believes that her sister’s reproductive problems were all linked to DES.
”Those were the days of miracle drugs, penicillin and the whole broad spectrum of antibiotics,” Pat Cody says. DES ”fit the pattern. We were very ready to accept it, believe me, and nobody ever thought about long-term effects.”