Medical Conditions among Adult Offspring prenatally exposed to DiEthylStilbestrol

DES Follow-up Study Summary

National Cancer Inst logo image
DES side-effects on Offspring exposed in Utero.

Concern about the possible impact of estrogen-like substances found in the environment on a range of health conditions has spurred research in this area. Diethylstilbestrol (DES) is an example of an endocrine-disruptor i.e., chemicals that interfere with the body’s hormone system. While prenatal exposure to DES is known to increase risks of vaginal or cervical cancer and poor reproductive outcomes in women, and abnormalities in the urinary and genital tracts in men information on non-reproductive medical conditions are lacking.

We studied the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis and related conditions among 5,590 exposed and unexposed daughters and 2,657 exposed and unexposed sons in the NCI Combined DES Follow-up Study. The associations took into account the participants’ birth year, sex, weight adjusted for height, smoking status, alcohol use, educational status, number of general physical examinations in the past 5 years, and study site.

Comparing participants exposed prenatally to DES with those who were not exposed, there were increases in the risk of developing cardiovascular disease (27%), heart attacks (28%), hypertension (14%), and high cholesterol (12%). In addition, the risks of developing diabetes, coronary artery disease, osteoporosis and fractures were elevated, but these findings were possibly due to chance. The associations of DES and the medical conditions did not differ by dose and timing of DES exposure, nor, in the women, by presence or absence of vaginal epithelial changes (a marker of DES host susceptibility).

This study raises the possibility that prenatal DES exposure is associated with several common medical conditions in adulthood, although there is the possibility that our results are explained by differences in the reporting of conditions by the exposed and unexposed participants, or by other factors related to both the conditions and DES exposure status that were not accounted for in the study, such as dietary intake and physical activity. We plan to continue to study these associations by obtaining medical records to confirm the diagnoses in the current round of the study.

DES Info commented: ” DES Exposure estimated hazard ratios and their associated 95% confidence intervals for the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis, and related conditions among 5590 female and 2657 male offspring followed from 1994 through 2006, adjusted for birth year, cohort, sex, body mass index, smoking status, alcohol use, education, and number of general physical examinations in the past 5 years “.

2013 Study Abstract:

BACKGROUND:
Diethylstilbestrol (DES), a synthetic estrogen that was used in pregnancy, is a prototype endocrine-disrupting chemical. Although prenatal exposure to DES is known to increase risks of vaginal/cervical adenocarcinoma and adverse reproductive outcomes in women, and urogenital anomalies in men, data on nonreproductive medical conditions are lacking.

METHODS:
We estimated hazard ratios and their associated 95% confidence intervals for the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis, and related conditions among 5590 female and 2657 male offspring followed from 1994 through 2006, adjusted for birth year, cohort, sex, body mass index, smoking status, alcohol use, education, and number of general physical examinations in the past 5 years.

RESULTS:
Comparing persons exposed prenatally to DES with those who were not exposed, the hazard ratios were 1.21 (95% confidence interval = 0.96-1.54) for diabetes, 1.27 (1.00-1.62) for all cardiovascular disease, 1.18 (0.88-1.59) for coronary artery disease, 1.28 (0.88-1.86) for myocardial infarction, 1.12 (1.02-1.22) for high cholesterol, 1.14 (1.02-1.28) for hypertension, 1.24 (0.99-1.54) for osteoporosis, and 1.30 (0.95-1.79) for fractures. The associations did not differ by dose and timing of DES exposure, nor, in the women, by the presence or absence of vaginal epithelial changes (a marker of DES host susceptibility).

CONCLUSIONS:
These data raise the possibility that prenatal exposure to DES is associated with several common medical conditions in adulthood, although differential reporting by DES status and residual confounding cannot be ruled out. Further follow-up should assess these findings with validated outcomes and seek to understand the biological mechanisms.

Sources:

  • Medical conditions among adult offspring prenatally exposed to diethylstilbestrol,NCBI, PMID: 23474687, 2013 May;24(3):430-8. doi: 10.1097/EDE.0b013e318289bdf7. Full text link.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

BPA-free Plastics going on Trial in Texas

Are BPA-free plastics really safe?

BPA-Free Plastics Going On Trial In Texas
PlastiPure helps manufacturers create water bottles and other plastic products that have no estrogenic activity

Scientists and lawyers are scheduled to debate the safety of certain “BPA-free” plastics this week in a U.S. District Court in Austin, Texas.

At issue is whether a line of plastic resins marketed by Eastman Chemical contains chemicals that can act like the hormone estrogen, and perhaps cause health problems.

Read BPA-Free Plastics Going On Trial In Texas, NPR Shots
by Jon Hamilton, 15 July 2013.

Related post:
Are BPA-free Plastics really safe?

Are BPA-free Plastics really safe?

Most Plastic Products release Estrogenic Chemicals…

Are BPA-Free Plastics Really Safe?
Scientists suspect thousands of chemicals may be estrogenically active

BPA is only part of the story. For their study, researchers tested more than 500 BPA-free consumer products for other estrogenically active chemicals and found that 92 % of the products readily leached the potentially hazardous compounds. Leaching was more common when products experienced ordinary stresses like dishwashing, microwaving and exposure to sunlight.

2011 Study Abstract

Background
Chemicals having estrogenic activity (EA) reportedly cause many adverse health effects, especially at low (picomolar to nanomolar) doses in fetal and juvenile mammals.

Objectives
We sought to determine whether commercially available plastic resins and products, including baby bottles and other products advertised as bisphenol A (BPA) free, release chemicals having EA.

Methods
We used a roboticized MCF-7 cell proliferation assay, which is very sensitive, accurate, and repeatable, to quantify the EA of chemicals leached into saline or ethanol extracts of many types of commercially available plastic materials, some exposed to common-use stresses (microwaving, ultraviolet radiation, and/or autoclaving).

Results
Almost all commercially available plastic products we sampled—independent of the type of resin, product, or retail source—leached chemicals having reliably detectable EA, including those advertised as BPA free. In some cases, BPA-free products released chemicals having more EA than did BPA-containing products.

Conclusions
Many plastic products are mischaracterized as being EA free if extracted with only one solvent and not exposed to common-use stresses. However, we can identify existing compounds, or have developed, monomers, additives, or processing agents that have no detectable EA and have similar costs. Hence, our data suggest that EA-free plastic products exposed to common-use stresses and extracted by saline and ethanol solvents could be cost-effectively made on a commercial scale and thereby eliminate a potential health risk posed by most currently available plastic products that leach chemicals having EA into food products.

BPS alters Hormones at Low Doses

Bisphenol S Disrupts Estradiol-Induced Nongenomic Signaling in a Rat Pituitary Cell Line: Effects on Cell Functions

BPA replacement alters hormones at low doses, study finds
Ultrasound images are printed on thermal paper that contains BPS

Just like the controversial Bisphenol A that it designed to replace, Bisphenol S chemical used in cash register receipts and other consumer products messes with hormones, according to research by University of Texas scientists. The study is the first to link low concentrations of BPS – a BPA alternative – to disruption of estrogen, spurring concern that it might harm human health. Researchers exposed rat cells to levels of BPS that are within the range people are exposed to…. and, just like BPA, the compound interfered with how cells respond to natural estrogen, which is vital for reproduction and other functions.

Read BPA replacement alters hormones at low doses, study finds
by Brian Bienkowski, Environmental Health News, Jan. 17, 2013.

Overall Incidence of Testicular Cancer on the Rise in the United States

Testis Cancer Rates Continue to Rise

Overall Incidence of Testicular Cancer on the Rise in the US
Testis cancer rates continue to rise

The incidence of testicular cancer has increased among American males over 15 years of age for more than 20 years and while overall incidence is still highest among Caucasian males, the greatest increase was observed in the Hispanic community, according to a new study at the 108th Annual Scientific Meeting of the American Urological Association.

DES Action USA commented: ” Experts speculate prenatal estrogen exposures may be to blame.  All men – and especially DES Sons – should practice testicular self-exam regularly!

Read Testis Cancer Rates Continue to Rise
By Charles Bankhead, MedPage Today, May 07, 2013

Sources: American Urological Association, May 03, 2013

Alterations in Estrogen Levels during Development affects the Skeleton: use of an Animal Model

Diethylstilbestrol DES side-effects on bones

Alterations in estrogen levels during development affects the skeleton: use of an animal model
DES side-effects on bones

Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. The recent finding of the presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of steroid hormones on bone tissue. Furthermore, estrogens have important effects on bone turnover in both humans and experimental animal models. Thus, this tissue is now regarded as a specific estrogen target tissue. To investigate whether a short-term developmental exposure to estrogens can influence bone tissue, we have injected female mice with diethylstilbestrol (DES) from day 1 through day 5 of life. Additionally, a group of pregnant female mice were injected with different doses of DES from day 9 through 16 of pregnancy. Mice were then weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (7-12 months of age). These short-term treatments did not affect body weight of exposed mice. However, a dose-dependent increase in bone mass, both in the trabecular and compact compartments, was observed in the DES-exposed female offspring. Furthermore, femurs from DES-exposed females were shorter than femurs from controls. A normal skeletal mineralization accompanied these changes in the bone tissue. In fact, a parallel increase in total calcium content of the skeleton was found in concomitance with the increase in bone mass. Estrogen treatment induced an increase in the amount of mineralized skeleton when compared to untreated controls. In summary, this report shows that alterations of estrogen levels during development can influence the early phases of bone tissue development inducing permanent changes in the skeleton. These changes appear to be related to bone cell programming in early phases of life. ”

Abstract, NCBI Endocrinology, October 1995  – Full text here

Related post: Alterations of maternal Estrogen Levels during Gestation affect the Skeleton of Female Offspring, May 1996.

More DES DiEthylStilbestrol Resources

Alterations of maternal Estrogen Levels during Gestation affect the Skeleton of Female Offspring

DES side-effects on bones

Alterations of maternal estrogen levels during gestation affect the skeleton of female offspring
DES side-effects on bones

Estrogens have important effects on bone turnover in both humans and experimental animals models. Moreover, the decreased level of estrogen after menopause appears to be one of the key factors in determining postmenopausal osteoporosis. The presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of these steroid hormones on bone tissue. Thus, this tissue is now regarded as a specific estrogen target tissue. Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. We have recently shown that transient developmental neonatal exposure (days 1-5 of life) of female mice to estrogen resulted in an augmented bone density in the adult animals. The aim of the present study was to evaluate whether short-term modification of maternal estrogen levels during pregnancy would induce changes in the skeleton of the developing fetuses and to identify any long-term alterations that may occur. Pregnant mice were injected with varying doses (0.1-100 micrograms/kg maternal BW) of the synthetic estrogen diethylstilbestrol (DES) from day 9-16 of pregnancy. Offspring were weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (6-9 months of age). Prenatal DES treatment(s) did not significantly affect BW. However, a dose-dependent increase in bone mass, both in the trabecular and cortical compartments, was observed in the prenatal DES-exposed female offspring. Furthermore, long bones of DES-exposed females were shorter than controls. Normal skeletal mineralization accompanied these changes in the bone tissue, as shown by a parallel increase in skeletal calcium content. Double tetracycline labeling performed in 6-month-old DES-exposed animals showed an increase in mineral apposition rate in adult DES-exposed mice as compared with untreated control animals, although no significant difference in the circulating estrogen levels was found in animals of this age. Experiments were then performed to evaluate whether perturbation of the estrogen surge at puberty in these diethylstilbestrol (DES)-exposed mice could reverse the observed changes. Femur length was chosen as a marker of potential estrogenic effect. Prepubertal ovariectomy of the prenatally DES-treated animals could only partially reverse the effects observed in the skeleton of the DES-treated animals. Further experiments were performed to evaluate whether these changes could have occurred in utero. CD-1 pregnant female mice were injected with DES (100 micrograms/kg maternal BW) from days 9-15 of gestation. On day 16 of gestation, fetuses were examined and stained by a standard Alizarin Red S and Alcian Blue procedure to visualize calcified and uncalcified skeletal tissue. Estrogen treatment induced an increase in the amount of calcified skeleton as compared with untreated controls and also a decrease in the length of long bones, strongly suggesting a change in both endochondral ossification and endosteal and periosteal bone formation. In summary, these data show, for the first time, that alterations in the maternal estrogenic levels during pregnancy can influence early phases of fetal bone tissue development and subsequently result in permanent changes in the skeleton. Finally, the effect of this short-term estrogen treatment can be seen in the fetal skeleton, suggesting an estrogen-imprinting effect on bone cell-programming in fetal life because treatment effects on bone cell turnover can be observed later in adult life. ”

Abstract, NCBI Endocrinology, May 1996 – Full text here

Related post: Alterations in Estrogen Levels during Development affects the Skeleton: use of an Animal Model, October 1995.

More DES DiEthylStilbestrol Resources

K-Cup® Plastic Products used under extensive Heat suspected of Estrogen Levels Rise

Cancer patients and survivors: are K-cups safe?

Cancer patients and survivors: Are K-cups safe?A sixty-year old plus friend recently shared an interesting testimony about how her estrogen levels had suddenly risen above a normal level, much to both her and her doctor’s surprise. As she began reviewing her daily eating and activity habits, she noticed only one major change in her behavior over the past several months: Since Christmas she had been regularly consuming coffee via Keurig cup containers … ”

Read Cancer patients and survivors: Are K-cups safe? pilotonline.com, Mar 31, 2013.

What about Plastics and Breast Cancer?

Choose Glass containers whenever possible!

So What About Plastics and Breast Cancer?You’ve heard stories about a compound found in plastic called BPA. It’s been linked to all sorts of health issues. So What about BPA and Breast Cancer?

BPA is an environmental estrogen, which means it increases your chances of developing breast cancer, especially when you’re exposed to it for many years.

Over time, it adds up, and this is why we see so many women, and some men, battling breast cancer today. Couple this with other ways you’re being exposed to estrogen, such as through building supplies, soy products and meat and dairy that are made from animals that have been injected with hormones.

When your body is overloaded with estrogen, your chances of breast cancer — or cancer period — are increased ; the DES-exposed know it too well…

SlideShow DES Books

Not just public health books but real stories of a tragedy experienced by million of men and women…

DES Books

DES Voices

 

The FlickrDES Booksphoto set features front cover images of a selection of books and publications in English and French about the adverse effects of Diethylstilbestrol, the synthetic oestrogen prescribed to millions of pregnant women around the world decades ago in the mistaken belief that it would reduce the risk of complications during pregnancy.  Below is a short introduction presenting these books:

BOOKS AND PUBLICATIONS IN ENGLISH

books about diethylstilbestrol image

Toxic Bodies: Hormones Disruptors and the Legacy of DES – Author Nancy Langston, published in 2011

In this gripping exploration, Nancy Langston shows how these chemicals have penetrated into every aspect of our bodies and ecosystems, yet the U.S. government has largely failed to regulate them and has skillfully manipulated scientific uncertainty to delay regulation. Personally affected by endocrine disruptors, Langston argues that the FDA needs to institute proper regulation of these commonly produced synthetic chemicals.

AFSSAPS DES Report – Author French Agency for the Safety of Health Products (AFSSAPS), published in 2011

As a result of a survey conducted in 2010, AFSSAPS decided to publish a DES update aimed at DES exposed individuals and health professionals. The publication emphasizes the gynecologists and obstetricians’ crucial role in recognizing DES exposure, informing their patients about its consequences and referring them to specialists for adequate care and monitoring. It also highlights the crucial role of DES patients in handing down the “record” of their exposure to the next generations. The AFSSAPS report is available to download in English and French.

Origins, How the Nine Months Before Birth Shape the Rest of Our Lives – Author Annie Murphy, first published in 2010

The book’s most chilling section involves the tragic results of thalidomide and diethylstilbestrol (DES), two drugs from the 1950s that were “given to pregnant women in the belief that the fetus would be unaffected.” Ms. Paul reveals six decades later: “It is evidence of the evolving state of our knowledge that the mechanisms by which these substances do their damage are not completely clear, even now.”

DES Voices, From Anger to Action – Author Pat Val Cody, published in 2008.

“Take a new estrogen promoted by the pharmaceutical companies. Add doctors ready to believe in another miracle drug. Take post-World War II women desperate to have a baby after miscarrying. Continue prescription for years. The result is the tragedy experienced by million of DES-exposed mothers, daughters, and son – and perhaps grandchildren. This is the story of what they did about the drug disaster that changed their lives.”

DES Stories, Faces and Voices of People Exposed to Diethylstilbestrol – Author Margaret Lee Braun, Theo Colborn and Nancy M.Stuart, first published in 2001

A tribute to the millions of lives upended by exposure to DES, diethylstilbestrol, synthetic estrogen, toxic chemical, and carcinogenic prescription drug. In photographic portraits and interviews, DES daughters, mothers, and sons tell, in their own voice, what it’s like to be DES-exposed. Today the DES story continues to unfold as research brings new findings to light. DES Stories rings with daring honesty—and points to broader concerns about the effects of endocrine-disrupting chemicals.

To Do No Harm: DES and the Dilemmas of Modern Medicine – Authors Dr. Apfel and Dr. Fisher, first published in 1985

In this important book, Drs. Apfel and Fisher demonstrate how explosive technological advances, physicians’ unconscious fantasies of heroism, and the urging of patients, among other factors, combined to produce the DES disaster-a massive tragedy that could occur again in any area of medicine.

DES Diethylstilbestrol – New Perspectives – Author David A. Edelman, first published in 1986

“An important contribution to the understanding of the uses of DES by pregnant women and the risks associated with this use. It is the only book on this subject that provides a scientifically objective overview and should be read by all who are involved in the debate over the effects of in utero DES exposure, including those men and women who were unfortunately exposed to the drug” American Medical Writers Association, July 1987.

BOOKS AND PUBLICATIONS IN FRENCH

Distilbène: des Mots sur un Scandale – Auteurs Véronique Mahé, publié en 2011

On estime le nombre de victimes du DES à 360 000 en France. Préfacé par Marie Darrieussecq, marraine du Réseau D.E.S. France, ce livre donne la parole aux femmes et aux hommes – mères et pères, filles et fils, compagnons – qui vivent les douloureuses conséquences de ce scandale médical, pour faire entendre leur souffrance et leur colère

DES (Distilbène – Stilboestrol): Trois Générations Réalités Perspectives – Auteur Anne Levadou, publié en 2010

Book presented by the support group Réseau D.E.S. France presenting texts from speakers of the DES symposium organized in France in November 2010.

Moi, Stéphanie, fille Distilbène –  Auteur Stéphanie Chevallier, publié en 2010

Stéphanie Chevallier est présidente de l’association des “Filles DES”. Elle est aujourd’hui l’heureuse maman d’un petit garçon adopté au Vietnam et poursuit son combat au nom des victimes du Distilbène grâce à son important rayonnement médiatique (elle est apparue dans Libération, Le Monde, etc…). Ce livre est son histoire et son combat contre l’ignorance face au DES.

Le Distilbène Trente Ans Après – Auteur Bernard Blanc, publié en 2008

Cet ouvrage est le fruit de la collaboration de plusieurs experts reconnus pour leur compétence dans ce domaine. Il intéressera tous les gynécologues obstétriciens, les urologues, mais aussi les médecins de santé publique et les sages-femmes.

Saskia ou le deuil d’un bébé Distilbène – Auteur Anne-Marie Lof, publié en 2000

Ce livre est le récit poignant d’une mère qui, sans le savoir, attend un « bébé Distilbène », du nom de ce médicament que l’on a donné aux femmes contre les nausées. Or, les filles des mères « contaminées » ont une propension aux fausse-couches et à d’autres pathologies. A partir de ce drame, Anne-Françoise Lof écrit un récit poignant dont le point de départ est la « non-existence » de l’enfant qui n’étant pas né, ni déclaré civilement, est tout de même né, même s’il était mort, une vraie personne, avec un vrai deuil, un vrai enterrement, une vraie souffrance. Elle s’appelait Saskia.

More DES DiEthylStilbestrol Resources