This post is part of The Pump Handle’s new “Public Health Classics” series exploring some of the classic studies and reports that have shaped the field of public health. Links to past posts in the series are available here. If you have a favorite Public Health Classic to recommend, let us know in the comments. And if you’re interested in contributing a post to the series, email us at email@example.com (send us a link to the report or study along with a sentence or two about what you find most interesting or important about it).
By Dick Clapp
Between 1940 and 1971, a synthetic form of estrogen called diethylstilbestrol (DES) was prescribed to pregnant women to prevent miscarriage and premature labor. This practice changed abruptly, though, after the New England Journal of Medicine published a dramatic new finding from a study of young women diagnosed with a rare cancer in two Boston hospitals. The authors of the study, using a hospital-based matched case-control design, reported a startling excess of clear cell adenocarcinoma of the vagina in women whose mothers had taken DES to prevent pregnancy loss. Seven of the eight cases were born to mothers who were prescribed and took DES during their pregnancy, while none of the mothers of the controls had taken the drug.
The probability of this outcome was estimated as less than 0.00001; although not reported in the published article, the odds ratio would have been infinity. Given the rarity of this cancer, and the strength of the association reported in this careful study, this result was so convincing that an accompanying editorial in the same issue of the journal said “it seems prudent for physicians to use caution in prescribing estrogenic substances during pregnancy.” This cautionary language was putting physicians on notice that prenatal exposure to DES appears to cause cancer in offspring. Later the same year, the U.S. Food and Drug Administration issued a Drug Bulletin for physicians saying the prescription of the drug was contra-indicated during pregnancy.
In the years following publication of this classic article, a large number of follow-up studies have been conducted. Cohorts of thousands of women who were prescribed DES were followed, and their female and male offspring were also followed for decades up until the present. This is one of the earliest examples of an endocrine-disrupting chemical causing direct harm to the women exposed and transgenerational effects in their offspring. A recent summary of the effects in daughters of women exposed during pregnancy noted significant increases in breast cancer, infertility, preterm delivery, stillbirth, early menopause and higher grade cervical abnormalities, among other adverse effects. The effects on male offspring are still being studied, but there is reasonably consistent evidence of increased testicular cancer and testicular abnormalities in DES sons. The full range of health effects in the offspring has probably not been documented, and attention is now being focused on DES grandchildren. What is already a tragedy may be still unfolding across generations.
There has also been social activism in the wake of the DES scandal. Since DES was given as a growth promoter to cattle, sheep and chickens, consumer activism and Congressional pressure led the FDA to ban any use of DES for this purpose in 1979. An organization called DES Action was formed in the 1970s, comprised of women who were mothers or daughters exposed during pregnancy, continues to the present. Some observers consider this organization to have been central to the transformation of women’s health politics over the past four decades; it is closely allied with the widely acclaimed Our Bodies, Our Selves, and has affiliated organizations in several European countries and Australia.
A movie by DES daughter Judith Helfand, called A Healthy Baby Girl, was produced in 1996, and its success led to a sequel called Blue Vinyl. A book by sociologist Susan Bell, titled DES Daughters has situated the activist response within a larger context of “embodied social movements” that challenge the entrenched power and perspectives of the medical and pharmaceutical industries. By some accounts, the HIV/AIDS advocacy organization Act-UP built upon and extended the DES example of an embodied social movement led by patients most directly affected by their exposure or disease.
On a personal level, I have been advised by or have been a colleague of several of the doctors and scientists who were involved in the original New England Journal of Medicine study and its follow-up. The late Dr. Howard Ulfelder was on my Massachusetts Cancer Registry Advisory Committee from its inception in 1980 and a wonderful, witty and wise advisor. Although most of the original group of young women patients were seen at Massachusetts General Hospital, Dr. Ulfelder claimed that they did not constitute a “cancer cluster.” Instead, he maintained that the cluster was a group of Ob/Gyn physicians standing in an MGH elevator discussing their patients. One of patients had told doctor that her mother had taken DES during pregnancy, and this led the other physicians to inquire about this in their patients. It was this information that led to the 1971 journal article and the causal connection it revealed.
Other colleagues at Boston University School of Public Health have continued to work on the follow-up studies and have co-authored many publications. Generations of students have learned the lessons of this calamity and their subsequent impact on public health. It is a cautionary tale that has had wide dissemination and bears updating and repeating for years to come.
Study citation: Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women. Herbst AL, Ulfelder H, Poskanzer DC. New Engl J Med 1971;284:878-81.
Dick Clapp, DSc, MPH is an epidemiologist who has forty years of experience in public health practice, research and teaching. He is Professor Emeritus at Boston University School of Public Health and Adjunct Professor at the U. of Mass.- Lowell School of Health and Environment. He is a former co-Chair of Greater Boston Physicians for Social Responsibility and served as Director of the Massachusetts Cancer Registry from 1980-1989.
6 thoughts on “Public Health Classic: DES Daughters”
I am a DES son! Even though some companies say that I am not. My mother took DES, 3 out of 4 members of my family have had a Des type of Cancer or DES related problem, One member died from the cancer.The 4th member I spoke of, my mother did not take DES with her. I am afraid for my 14 year old daughter. Please keep the studies going because I believe the damage DES can cause is still ongoing, Jonathan
A question from a DES daughter: Was there ever good evidence that DES actually prevented miscarriages? Or was this just the medical fashion? I was aware of being a DES Daughter only because my mom’s doctor had sung the praises of the stuff back in the 1960’s, and she believed him: allegedly, I was a “child of Science” who could not have been born without this drug. I had heard since that the prior child she lost had been male, and they’re more prone to miscarry, so that might have explained her success carrying me to term.
Many thanks for this blog! As a workers comp advocate I read it constantly.
Thanks for your pertinent question. My review of the literature, plus a meta-analysis of studies in the literature in 1995 by Macarthur and colleagues (J Clin Epidemiol 1995;48(6):739-747) suggests that there was no good evidence that DES actually prevented miscarriages. Your point about your being a daughter, rather than a son is also relevant. There is an adage that males have a higher risk of dying than females at every age from conception onward.
Thanks, Dick! I guess being a Child of Science ain’t all it’s cracked up to be. Much less a child of Big Pharma … yikes.
Hi, I am writing a novel – Silent Trauma, fiction built on fact – about DES. I am in contact with Fran Howell Director of DES Action USA, who has given her permission for me to use quotes from various DES sources. I would be grateful if you would allow me to use a couple of sentences from your article as a quote at the beginning of a chapter. I have a website http://www.judithbarrow.co.uk
Warm Regards Judith