The Diethylstilbestrol Legacy

A Powerful Case Against Intervention in Uncomplicated Pregnancy

2016 Report Abstract

Although the basic tenet of medicine is “First, do no harm,” history is filled with good intentions that were at best unhelpful and at worst harmful. Because medicine seeks to cure afflictions, there is an overwhelming desire on the part of health providers and patients to administer treatment. In certain settings, treatment can be reasonable despite a risk of adverse consequences: for example, if the disease is cured or its morbidity abated and the treatment consequences are less disabling than the disease itself.

In the absence of overt disease, the question of whether to apply an intervention is far more challenging. The safety of interventions must be weighed against the population’s level of risk, the morbidity and/or mortality associated with the disease, and the intervention’s efficacy (eg, BRCA1 mutation, mastectomy, reduced breast cancer risk). Interventions must meet an especially high standard of safety and efficacy when administered in low-risk populations or in settings in which the morbidity associated with the disease is minor. In the worst-case scenario, an intervention may be both ineffective for its primary purpose and cause iatrogenic illness.

The Diethylstilbestrol Legacy: A Powerful Case Against Intervention in Uncomplicated Pregnancy,
Pediatrics, November 2016, VOLUME 138 / ISSUE Supplement 1, Supplement_1/S42.abstract, November 2016.

Interventions in pregnancy are especially problematic because of the complex physiology of the condition and the possibility of causing short- and long-term adverse consequences in both the mother and her offspring. The continuing story of diethylstilbestrol (DES), a synthetic estrogen, shows the importance of caution when evaluating the merits of interventions involving pregnant women. With regard to DES, investigators believed that pregnancy loss was caused in part by a decrease in estrogen and that administering DES to pregnant women would help maintain a healthy pregnancy. Moreover, because endogenous estrogen concentrations increase dramatically during a healthy pregnancy, supplementation with DES was deemed harmless. During its early years of use, DES was administered to women with threatened pregnancy loss or a history of pregnancy loss. Eventually, DES was advertised to the medical community for “routine prophylaxis in ALL pregnancies” and administered to women with otherwise healthy pregnancies.

By the time DES was formally evaluated, it was standard of care in high-risk obstetrics practices. The first clinical trial to determine the efficacy of DES, reported in 1953, showed that DES did not improve pregnancy outcome. (Indeed, a subsequent reanalysis of the data revealed that DES increased the risk of spontaneous abortion, preterm birth, and neonatal death) Despite lack of evidence supporting a benefit, DES continued to be prescribed during pregnancy until 1971, when a small study showed a stunning 40-fold increase in the risk of clear cell adenocarcinoma (CCA) of the vagina and cervix in girls and young women who were prenatally exposed to DES. Several months later, the Food and Drug Administration issued a bulletin indicating that the use of DES was contraindicated in pregnancy. By then, however, millions of women, along with their sons and daughters, had been needlessly exposed.

In addition to the increased risk of CCA of the vagina and cervix, daughters exposed in utero to DES also suffered from an increased occurrence of reproductive tract abnormalities, infertility, and pregnancy complications; earlier menopause; twice the incidence of cervical dysplasia; and a possible elevated risk of breast cancer and continued increased risk of CCA in middle age. Recent preliminary data indicate the possibility of an increased risk of cardiovascular disease and diabetes in the prenatally exposed women. Mothers administered DES during pregnancy have an increased risk of breast cancer incidence and mortality. Sons who were exposed in utero have an increased risk of genitourinary defects and a possible increase in testicular cancer. The possibility of epigenetic transmission with consequent adverse outcomes in the offspring of prenatally exposed women is under investigation. Preliminary findings showed increased menstrual irregularity and a possible excess of ovarian cancer in very young women.

The link between prenatal DES exposure and subsequent adverse health outcomes, most of which are fairly common, may easily have escaped detection. The investigation of DES outcomes was initiated solely because a rare tumor occurred in a cluster of cases at an unusually young age, decades before the usual age of presentation. This historical example underscores the necessity of carefully weighing the risks and benefits of interventions in pregnancy and long-term monitoring of the health outcomes in mothers and offspring.

Whether and/or when to use pharmaceutical intervention in pregnancy continues to pose special challenges. At the present time, progesterone used to prevent pregnancy loss appears to be effective, although more data are needed. Thus far, there is little evidence of short-term adverse consequences for the offspring, but continued monitoring of mothers and offspring is warranted to identify any short- or long-term adverse effects. The use of progestins for luteal phase and early pregnancy support after in vitro fertilization is routine, and there are even fewer data on potential short- and long-term risks of this therapy. The tragic legacy of DES supports a cautious approach to the use of pregnancy interventions and assiduous appraisal of their effects.

Rebecca Troisi, Elizabeth E. Hatch, Linda Titus,
Reviewed by Dr Robert Hoover,

Click to download the full paper.

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Cancer Risk in Women Exposed to Diethylstilbestrol in Utero

Significant increase of breast cancer in DES Daughters

2015 Study Abstract

OBJECTIVE
To evaluate the overall cancer risk, primarily breast cancer, for women exposed to diethylstilbestrol (DES) in utero in France.

METHODS
A cohort of 3 436 prenatally DES exposed women and a comparable cohort of 3256 unexposed women were recruited retrospectively from voluntary responses to questionnaires, and cases were ascertained by medical history at the time of recruitment.

Cancer Risk in Women Exposed to Diethylstilbestrol in Utero, US National Library of Medicine National Institutes of Health, Therapie, NCBI PubMed PMID: 26071143, 2015 Sep-Oct.

Image credit Amy the Nurse.

RESULTS
One hundred ninety-five cancers were observed in exposed women (136 breast cancers, and 59 in other sites) and 141 cancers in unexposed women (90 breast cancers, and 51 others). A significant increase of breast cancers was found in exposed women, with a multivariate incidence rate ratio of 2.10 (95% CI 1.60-2.76) when compared with unexposed women. When exposed women were compared with the general population in France, the standardized incidence ratio was 2.33 (95% CI 1.93-2.72).

CONCLUSION
Our results suggest a significant increase of breast cancer in prenatally DES exposed women when compared with unexposed women and with the general population. For other cancers, except clear cell carcinoma of the cervix or vagina, there was a global non-significant increase.

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Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome

A national survey of DES daughters and unexposed controls

2017 Study Abstract

To explore whether prenatal exposure to diethylstilbestrol (DES) is associated with increased risk of poor psychological outcome independently of the occurrence of major somatic complications related to DES exposure.

Data on health outcome were collected in women prenatally exposed to DES (n = 2566) and unexposed women (n = 2967) recruited in a French national survey.

Women prenatally exposed to DES were 1.7 times more likely to have consulted a mental health specialist compared to unexposed women (adjusted odds ratio = 1.69, 95% confidence interval 1.47-1.96), independently of demographic characteristics, poor gynecological or obstetrical outcome, or history of cancer.

Impact of prenatal exposure to diethylstilbestrol (DES) on psychological outcome: a national survey of DES daughters and unexposed controls, US National Library of Medicine National Institutes of Health, Archives of women’s mental health, NCBI PubMed PMID: 28064340, 2017 Jan 7.

Image credit Alessandra.

Frequency of consultation with a mental health specialist in persons with a history of gynecological complications or cancer was comparable in women prenatally exposed to DES and unexposed women.

Findings regarding psychological outcome obtained in the high-risk group of women prenatally exposed to DES may contribute to improving identification of psychological needs of all women presenting with gynecological abnormalities.

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14 Filles Distilbène, telles qu’elles sont…

3’35 pour “parler” autrement du DES…

Vidéo publiée le 13 janvier 2017 par la chaine Association Réseau DES FRANCE DISTILBENE.

Une série de portraits de femmes touchées, traversées, abîmées par le Distilbène DES.

“Je veux que chaque femme touchée par le DES dans le monde puisse s’y retrouver : française, américaine, australienne, hollandaise, africaine, allemande… Je veux que ce témoignage muet soit entendu dans toutes les langues par toutes les cultures. Je souhaite qu’il permette aux femmes qui y participeront de déposer quelque chose derrière la caméra et de repartir plus légères et fières du courage qu’elles ont eu à le faire. Je veux que la gravité et la beauté de ces visages sans mots résonnent puissamment aux oreilles des lobby, dans les couloirs de la commission européenne, dans l’antichambre des tribunaux où se rejoue David contre Goliath à chaque procès de ‘fille DES’ “

Laetitia Dormoy, créatrice du projet.
Sources : la chronique de Marie Darrieussecq.

Le Distilbène DES, en savoir plus

Normal vs. T-shaped Uterus

Utero-salpingography showing Diethylstilboestrol exposure in-utero uterus

Diethylstilboestrol (DES) exposure in-utero has been shown to have a potentially negative impact on pregnancy. Negative effects include an increased risk of early pregnancy loss, ectopic gestation and infertility.

These women may also present reproductive tract abnormalities leading to pregnancy complications. The most common anomalies include uterine defects such as T-shaped uterus or hypoplastic uterine cavity.

Image Sources

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Getting Your Period when you are a Young DES Daughter…

The Devastating Effects of a 1940s ‘Wonder Pill’ Haunt Women Generations Later

” In the throes of puberty,14-year-old Su Robotti had developed “humongous breasts,” but she was still waiting for what she really wanted: her period. The year was 1969, and Robotti was filled with anxiety as she watched her friends, one-by-one, come to school and report that they had begun menstruating. All the while, she kept quiet, agonizing over when she’d ruin her first pair of underwear. At times, she even considered lying about it, but nervous thoughts would always inevitably halt her—she couldn’t even pretend she knew what cramps felt like.

Robotti’s mother, who had gotten her period when she was 12, was less anxious and more worried. At her mother’s insistence, Robotti found herself reclining in a gynecological chair. She watched as a doctor massage her lower abdomen as part of an external pelvic exam, and then listened to him deliver the report to her mother: Her reproductive organs were infant-sized and she only had one working ovary.

“I just felt like I wasn’t enough,” remembers Robotti today. At 59 years old, Robotti still hasn’t gotten her first period—and she never will. Robotti is a “DES daughter, …”

… continue reading The Devastating Effects of a 1940s ‘Wonder Pill’ Haunt Women Generations Later by Amanda Arnold on broadly, JAN 5 2017.

DES DiEthylStilbestrol Resources

Analyse comparative de familles victimes du Distilbène et d’agriculteurs victimes des pesticides

Coline Salaris, Science politique. Université de Bordeaux, 2015

Résumé

Se présenter comme victime et se mobiliser en tant que telle dans l’espace public ne va pas de soi, même pour les membres d’une association de victimes. Il s’agit d’un long processus d’intériorisation et de reformulation identitaires consistant à donner du sens à une expérience de souffrance ; une pathologie ou un deuil. Pour les membres d’un collectif de victimes se mobilisant dans le cadre d’un problème de santé publique, il s’agit aussi d’un processus d’ordre collectif consistant à construire un groupe suffisamment cohérent pour imposer des griefs a priori personnels, comme problème public de santé.

Mobilisations en souffrance : analyse comparative de la construction de deux problèmes de santé publique : (familles victimes du Distilbène et agriculteurs victimes des pesticides), Coline SALARIS, THÈSE PRÉSENTÉE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE BORDEAUX, 3 décembre 2015.

Hal-SHS Archives Ouvertes, halshs-tel-01278157, 2015.

C’est de ces multiples processus, à la fois individuels et collectifs, entre intime et public que se propose d’analyser cette thèse. En nous appuyant sur une enquête comparative entre l’affaire du Distilbène et la mobilisation de travailleurs agricoles victimes des pesticides – qui croise 77 entretiens semi-directifs et une quinzaine d’observations ethnographiques des temps qui articulent ces mobilisations -, nous nous sommes demandée comment des individus dispersés et blessés parviennent progressivement et collectivement à s’imposer comme des acteurs d’action publique, et plus précisément des acteurs de la santé publique.

Coline SALARIS, halshs-01278157
Science politique. Université de Bordeaux, 2015.

Le Distilbène DES, en savoir plus

Over 50 years later, DES’ adverse effects continue

Women Exposed to DiEthylStilbestrol In Utero Face Ongoing Risks for Adverse Health Outcomes

October 8th, 2011, NEJM Journal Watch talked with two authors of the reportAdverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol“.

Press Play > to listen to the recording.

Sources and more information

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T-shape uterine cavity, typical of the DES syndrome

Utero-salpingography showing Diethylstilboestrol exposure in-utero uterus

Diethylstilboestrol (DES) exposure in-utero has been shown to have a potentially negative impact on pregnancy. Negative effects include an increased risk of early pregnancy loss, ectopic gestation and infertility.

These women may also present reproductive tract abnormalities leading to pregnancy complications. The most common anomalies include uterine defects such as T-shaped uterus or hypoplastic uterine cavity.

Image Sources

  • Estradiol and progesterone supplementation during luteal phase improved the receptivity of the endometrium in a patient with a history of diethylstilboestrol exposure in-utero, hormones.gr, 2006.
  • Watch our DES and EDCs Research album on Flickr.
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Above the Fog

A Life Journey with DES

above-the-fogAbove the Fog is a powerful story of one women’s struggle with DES (diethylstilbestrol).

The drug was developed in 1937 as the first synthetic estrogen. Millions of pregnant women who had previous miscarriages or premature births were given this drug in hopes of correcting the problem with their pregnancies.

Years later the tragic results started showing up in the daughters and later on in the sons – but the FDA did not contraindicated this drug until 1971 to all pregnant women.

This story is about one women, who never gave up in the face of her repeated health issues caused by DES or her family’s extraordinary health problems. She was determined to face the hard times with dignity and grace.

Author: Sue Carver, a wife, mother and grandmother based in Sequim Washington for the past 42 years.
Publisher: Outskirts Press, Inc.
Publication date:08/05/2016
Pages:230

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