DiEthylStilbestrol Resources: Gestational DES-Exposure and Side-Effects

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In-Utero Exposure to DES

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NCBI PubMed DiEthylStilbestrol Resources: Fetal DES-Exposure and Side-Effects.

DES Side Effects

– Bones

– Endometriosis

– Menarche

– Menopause

– Obesity

– Various Studies

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No Reason to use Hormone Replacement Therapy to boost Mental Well-Being after Periods Stop

HRT: Estrogen Won’t Make Women Sharper After Menopause

Estrogen Won't Make Women Sharper After Menopause, Study Finds
Low levels of the hormone #estrogen are not to blame for mood swings and poor memory after #menopause, a new study suggests.

Low levels of the hormone estrogen are not to blame for mood swings and poor memory after menopause, a new study suggests.

Based on this finding, the researchers believe there’s no reason to use hormone replacement therapy to boost mental well-being after periods stop.

Abstract:

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (-6 y after menopause) and late (10+ y after menopause) groups. Women were administered a comprehensive neuropsychological battery and assessed with the Center for Epidemiologic Studies Depression Scale. They provided serum for free estradiol, estrone, progesterone, free testosterone, and sex hormone binding globulin measurements. Cognitive outcomes were standardized composite measures of verbal episodic memory, executive functions, and global cognition. Covariate-adjusted linear regression analyses were conducted for each hormone separately and after adjustment for other hormone levels. Endogenous sex steroid levels were unassociated with cognitive composites, but sex hormone binding globulin was positively associated with verbal memory. Results for early and late groups did not differ significantly, although progesterone concentrations were significantly positively associated with verbal memory and global cognition in early group women. Hormone concentrations were not significantly related to mood. Results fail to support the hypothesis that temporal proximity to menopause modifies the relation between endogenous serum levels of estradiol and verbal memory, executive functions, or global cognition. Physiological variations in endogenous postmenopausal levels of sex steroid hormones are not substantially related to these aspects of cognition or mood; positive associations for progesterone and sex hormone binding globulin merit additional study.

Sources:

Estrogen Won’t Make Women Sharper After Menopause, Study Finds, healthday, 25 Nov 2013

Cognition, mood, and physiological concentrations of sex hormones in the early and late postmenopause, PNAS, 23 Oct 2013

Supporting Information, Henderson et al. 10.1073/pnas.1312353110

More information:

Testosterone Treatments linked to Risk of Heart Problems and Deaths

Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

Due to increased marketing, rates of testosterone prescription in the U.S. tripled between 2000 and 2011…

2013 Study Abstract

Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels
The Journal of the American Medical Association, published since 1883, is an international peer-reviewed general medical journal published 48 times per year

Importance:
Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. A recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.

Objectives:
To assess the association between testosterone therapy and all-cause mortality, myocardial infarction (MI), or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease.

Design, Setting, and Patients:
A retrospective national cohort study of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011.

Main Outcomes and Measures:
Primary outcome was a composite of all-cause mortality, MI, and ischemic stroke.

Results:
Of the 8709 men with a total testosterone level lower than 300 ng/dL, 1223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).

Conclusions and Relevance:
Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.

Rates of testosterone therapy prescription have increased markedly in the United States over the past decade. Annual prescriptions for testosterone increased by more than 5-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion in 2011. Professional society guidelines recommend testosterone therapy for patients with symptomatic testosterone deficiency. In addition to improving sexual function and bone mineral density and increasing free-fat mass and strength treatment with testosterone has been shown to improve lipid profiles and insulin resistance and increase the time to ST depression during stress testing.

The effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. Prior clinical studies of testosterone therapy have not detected adverse cardiac events, but these trials were generally focused on intermediate end points, of short duration, and not powered for clinical end points. A recent trial, the Testosterone in Older Men with Mobility Limitations (TOM) trial, conducted in older frail men with a high prevalence of cardiovascular diseases was stopped prematurely due to increased cardiovascular events in the treatment group. The premature termination of the TOM trial and the limitations of the prior studies highlight uncertainty regarding the safety of testosterone therapy in older men with cardiovascular diseases.

To address this gap in knowledge, we evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction (MI), and stroke among male veterans and whether this association was modified by underlying coronary artery disease (CAD).

Comment (2019)

Endocrine Disruptors stunt Penile and Testicular Development

Evolution or Extinction of Men?

ENDOCRINE DISRUPTORS AND YOUR SON’S PENIS SIZE
Hormone research matters is @LucineWoman on Twitter

We write a lot about endocrine disruptors here at Hormones Matter™ and for whatever strange twist of fate, we seem to cover a lot of research on penis size. Believe it or not, the two are related. Endocrine disruptors are largely estrogenic in nature and when exposure occurs during certain developmental time periods, those estrogens affect penis size, form and function.

Continue reading ENDOCRINE DISRUPTORS AND YOUR SON’S PENIS SIZE, by CHANDLER MARRS, PHD, MARCH 2013.

 

Hormone Replacement Therapy: natural Form of Hormone much better than Synthetic Estrogen

Less Blood Clot Risk Linked to Estradiol Than to Premarin Pills

Less Blood Clot Risk Linked to Estradiol Than to Premarin Pills
Higher risk of incident venous thrombosis and possibly myocardial infarction with the Premarin drug

Women can choose among several types of estrogen pills, which are equally effective at relieving menopausal symptoms. In a head-to-head comparison of two major forms of hormone replacement therapy, a more natural version of estrogen proved less dangerous to the heart than a synthetic one – a patented drug marketed as Premarin.

Read Less Blood Clot Risk Linked to Estradiol Than to Premarin Pills, Science News, 30 Sept 2013.

Read Synthetic Estrogens Pose Greater Clot Risk Than Natural Forms of Hormone, by Alexandra Sifferlin, 1 Oct 2013.

Sources: Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared With Oral Conjugated Equine Estrogens, JAMA, 30 Sept 2013.

More about estrogens and hormone replacement therapy.

Exposure to Synthetic Estrogens at different Times during the Life and their Side Effects on Health

Synthetic Estrogens exposures induce epigenetic modifications for multiple generations

2013 Study Abstract:

Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk
Synthetic Estrogens exposures induce epigenetic modifications for multiple generations

Women are using estrogens for many purposes, such as to prevent pregnancy or miscarriage, or to treat menopausal symptoms. Estrogens also have been used to treat breast cancer which seems puzzling, since there is convincing evidence to support a link between high lifetime estrogen exposure and increased breast cancer risk. In this review, we discuss the findings that maternal exposure to the synthetic estrogen diethylstilbestrol during pregnancy increases breast cancer risk in both exposed mothers and their daughters. In addition, we review data regarding the use of estrogens in oral contraceptives and as postmenopausal hormone therapy and discuss the opposing effects on breast cancer risk based upon timing of exposure. We place particular emphasis on studies investigating how maternal estrogenic exposures during pregnancy increase breast cancer risk among daughters. New data suggest that these exposures induce epigenetic modifications in the mammary gland and germ cells, thereby causing an inheritable increase in breast cancer risk for multiple generations.

2013 Study Conclusion:

Women use estrogens for many purposes. During pregnancy, synthetic strogen DES was used to prevent miscarriage and promote healthy pregnancy, although it turned out to cause the opposite. During the reproductive years when a woman’s own estrogen levels are high, women use synthetic estrogens as contraceptives. Since estrogens play an important role in normal physiological functions in women, some menopausal and postmenopausal women use estrogen supplementation to regain the benefits of natural estrogens.

The effects of estrogens on breast cancer risk differ depending upon when during a woman’s life time they are used. Maternal exposure to DES during pregnancy increases breast cancer risk in mothers and their daughters. The adverse effects of synthetic estrogen exposure during pregnancy may not be limited to mothers and their daughters. Our preclinical study in rodents showed that maternal exposure to EE2 increases breast cancer risk in daughters, granddaughters, and great granddaughters. The first generation of OCs increased breast cancer risk at the time women were taking them, but the increase in risk was not permanent. The current, third generation contraceptives do not increase breast cancer risk. Menopausal and postmenopausal HT, if it contains both estrogens and progestin, increases a woman’s breast cancer risk, and recent data suggest that tumors developing during therapy are more aggressive than those in women not using HT. Estrogen-only HT does not increase breast cancer risk, and might even reduce it. However, due to other adverse effects of estrogen-only HT, it is not recommended beyond using it to control the most severe menopausal symptoms.

We are beginning to understand how the increase in breast cancer risk following in utero exposures to synthetic estrogens occurs. It most likely involves long-term epigenetic changes in genes that are important in determining the risk for breast cancer development, such as tumor suppressor genes, PcTGs and oncogenes. Briefly, an exposure to synthetic estrogens during the fetal period induces modifications in the epigenetic reprogramming of the genome, leading to changes in mammary gland morphology, and gene and protein expression. Some of these changes are transient, such as an increase in the number of TEBs in rodents, and some persist, such as an altered gene and protein expression involving tumor suppressor genes and oncogenes. Together, epigenetically induced modifications in the mammary gland morphology and gene expression increase the likelihood that environmental carcinogens and radiation induce malignant transformation, and evetually breast cancer. The next challenge is to determine whether the increase in risk can be reversed by reversing epigenetic changes that occur as a consequence of early life exposure to synthetic estrogens.

Additional Information : Exposures to Synthetic Estrogens at Different Times During the Life, and Their Effect on Breast Cancer Risk, Springer, Journal of Mammary Gland Biology and Neoplasia, Volume 18, Issue 1, March 2013, Special Issue: Environmental Risk Factors. Full text on NCBI PMC3635108.

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U.S. PSTF advise to use Hormone Replacement Therapy for only short periods of Time

U.S. Panel Warns Hormone Replacement Therapy Is Too Risky

Postmenopausal Hormone Replacement Therapy for Primary Prevention of Chronic Conditions: Recommendations and Rationale
Alexandra Sifferlin is a reporter for TIME Health and Family

In their November 2002 recommendations, the U.S. Preventive Services Task Force confirmed that the risk of HRT outweigh its potential benefits.

The USPSTF recommends against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women ; advising women to use HRT to treat symptoms of menopause for only short periods of time.

Read U.S. Panel Warns Hormone Replacement Therapy Is Too Risky
by Alexandra Sifferlin, 23 Oct 2012

Read Panel Advises Against Hormones to Prevent Disease
by Brenda Goodman, WebMD Health News, 22 Oct 2012.

Sources: Postmenopausal Hormone Replacement Therapy for Primary Prevention of Chronic Conditions: Recommendations and Rationale
U.S. Preventive Services Task Force, 19 Nov 2002.

All our posts about EstrogenHRTMenopause.

Behavioral and somatic Disorders in Children Exposed in Utero to Synthetic Hormones

A Testimony-Case Study in a French Family Troop, 2012

Behavioral and Somatic Disorders in Children Exposed in Utero to Synthetic Hormones: A Testimony-Case Study in a French Family Troop
French study reveals serious DES psychological side effects in DES Daughters and DES Sons

Using a familial case control study, Marie-Odile Soyer-Gobillard – former director emeritus at the CNRS (French National Center for Scientific Research) – and Charles Sultan show that there are serious effects on the psychological and physical health of the descendants of women treated with synthetic hormones during their pregnancy: psychiatric illnesses are often found associated with somatic disorders which are well known to be the DES and EE signature. Synthetic hormones, acting as endocrine disturbers, are toxic for humans, especially for pregnant women and their children, probably partly in relation with their toxic degradation status. In all cases girls suffered more than boys either of somatic and/or psychiatric disorders due to the estrogen receptor alpha or beta concentration higher in female fetus than in male. It is also clear that in all the families most of the exposed children are ill while quite the unexposed are not.

2012 Study Overview:

  • Materials and methods: Gathering questionnaires and the evidence
  • Results / Data Analysis / Discussion
  • A multi-generational effect? By what mechanism?
  • Conclusion

Read Behavioral and Somatic Disorders in Children Exposed in Utero to Synthetic Hormones: A Testimony-Case Study in a French Family Troop by Marie-Odile Soyer-Gobillard, Charles Sultan (2012), Dr. Sameh Magdeldin (Ed.), ISBN: 978-953-51-0772-9, InTech, DOI: 10.5772/48637.

Related posts:

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Preterm Birth, Fetal Growth, Age at Menarche among Women exposed prenatally to DiEthylStilbestrol

DES exposed daughters more likely to have begun menstruating at younger age

DES Follow-up Study Summary

National Cancer Inst logo image
DES exposed daughters appeared to weigh slightly less and have a higher risk of being born prematurely than unexposed daughters. They also were somewhat more likely to have begun menstruating at age 10 or younger.

Research has suggested that early life characteristics, such as size at birth and age at menarche, may be associated with health conditions later in life. For example, some studies have suggested that low birth weight babies tend to have a higher risk of cardiovascular disease later in life. Other studies have shown that women who begin having periods at a young age have a slightly higher risk of breast cancer than those who begin menstruation later.

Although there has been a great deal of research on health of the 2nd generation (DES daughters) later in life, little attention has been paid to whether they were similar in terms of birth weight and other early life factors. Results from one of the early clinical trials of DES suggested that it might be related to lower birth weight and a higher risk of preterm birth. We conducted a systematic evaluation of DES daughters participating in the NCI DES Follow-up Study to determine whether there were any differences in birth weight, length of gestation, and the average age of first menstruation in the DES-exposed compared to unexposed daughters.

We found that there was a 2 to 3 fold increase in risk of having been born prematurely (before 37 weeks gestational age) among the DES-exposed compared to unexposed daughters. On average, DES daughters tended to weigh slightly less at birth, and there was also a 60% higher risk of being born too small, or small for gestational age (SGA), defined as less than the 10th percentile of birth weight at each gestational age. We found stronger effects for birth weight, SGA, and preterm birth among women who were participants in the original DESAD study, as compared to those who were in the Dieckmann clinical trial, suggesting that part of the effect may have been due to the higher risk pregnancies among the exposed women and not solely to DES exposure.

When we evaluated the risk of having started menstruation before age 11, we found no difference between the DES exposed and unexposed daughters. However, DES daughters did have a small increased risk (40%) of starting menarche very young-at age 10 or less-but this was based on very small numbers of participants who had very early menstruation.

In summary, DES exposed daughters appeared to weigh slightly less and have a higher risk of being born prematurely than unexposed daughters. They also were somewhat more likely to have begun menstruating at age 10 or younger. These effects may have a small impact on the risk of some diseases occurring later in life.

2011 Study Abstract:

Diethylstilbestrol (DES), a synthetic estrogen used in pregnancy during the 1950s and 1960s, provides a model for potential health effects of endocrine disrupting compounds in the environment. We evaluated prenatal exposure to DES, based on medical record review, in relation to gestational length, fetal growth, and age at menarche in 4429 exposed and 1427 unexposed daughters. DES exposure was associated with an increase in preterm birth (odds ratio (OR)=2.97; 95% CI=2.27, 3.87), and a higher risk of small for gestational age (SGA) (OR=1.61; 95% CI=1.31, 1.98). The association between DES exposure and early menarche was borderline, with stronger effects when early menarche was defined as ≤ 10 years (OR=1.41 95% CI=0.97, 2.03) than defined as ≤ 11 years (OR=1.16; 95% CI=0.97, 1.39). This study provides evidence that prenatal DES exposure was associated with fetal growth and gestational length, which may mediate associations between DES and health outcomes in later life.

Sources:

  • Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES),NCBI, PMID: 21130156, 2011 Feb;31(2):151-7. doi: 10.1016/j.reprotox.2010.11.006. Epub 2010 Dec 2. Full text link.
  • NCI, DES Follow-up Study Published Papers.
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DiEthylStilbestrol DES: a Cautionary Tale…

Disrupted Development: The Dangers of Prenatal Estrogen Exposure

Read:
DES: a Cautionary Tale

Abstract:

The drug diethylstilbestrol (DES) provides a striking andtragic example of the effects of prenatal exposures to chemicals that disrupt our hormones. DES was initially synthesized by a research team in London that had been searching for compounds that could be used for estrogen replacement during menopause, then referred to as deficiency disease. DES was approved by the FDA in 1941 to prevent miscarriages. It was prescribed to pregnant women for this purpose until 1971.

Early systematic studies failed to find evidence that DES was effective at preventing miscarriages but it continued to be prescribed to pregnant women. The wide use of DES created an accidental experiment that led to 5 to 10 million pregnant women – and the children born from those pregnancies – being exposed to this synthetic estrogen.

From 1966 to 1969, doctors at the Vincent Memorial Hospital in Boston noted a pattern of rare vaginal cancers in young women. These cancers were rare even in women over 50, and the hospital had never seen a single case of that specific type of cancer in younger women prior to 1966. The doctors conducted a study to determine similarities among the women, and found that the common thread was their mothers’ use of DES during their pregnancies. The doctors published a paper reporting
their findings in the New England Journal of Medicine in 1971, after which DES prescriptions were halted.

Since 1971, further research has linked prenatal DES exposure to a nearly two-fold increase in breast cancer among women over 40, and even higher rates among women over 50. Women who were presumed to have the highest exposures to DES (estimated based upon how much their vaginal cells were altered) had a higher risk of breast cancer.

The story of DES provides a cautionary tale about prenatal exposures to chemicals that can mimic the body’s own hormones. BPA is one such compound – In fact, BPA was even considered as an estrogen replacement by the same London laboratory that first created DES. As the DES story underscores, it can take decades to recognize the long-term health effects of early exposures to hormone-disrupting compounds in the general population, making it even more critical that we act on early warnings of harm. ”

Sources: Breast Cancer Fund’s report ” Disrupted Development: The Dangers of Prenatal BPA Exposure “, a comprehensive review of the scientific literature on prenatal BPA exposure, just-released.

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