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

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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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DiEthylStilbestrol Resources: Cancer, Breast Cancer, CCAC, Vaginal Cancer, Screening

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Cancer

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NCBI PubMed DiEthylStilbestrol Resources: Cancer, Breast Cancer, CCAC, Vaginal Cancer, Screening.

– Breast Cancer

– Clear Cell AdenoCarcinoma and Vaginal Cancer

– Screening

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Vaginal and Cervical Abnormalities, including CCA, related to PreNatal Exposure to Stilbestrol

In utero DES exposure associated with severe clear-cell adenocarcinoma in DES Daughters

Vaginal and cervical abnormalities, including clear-cell adenocarcinoma, related to prenatal exposure to stilbestrol
In utero exposure to Stilbestrol associated with severe clear-cell adenocarcinoma in DES Daughters

A variety of vaginal and cervical abnormalities have been encountered in the offspring of women who have taken stilbestrol or chemically related nonsteroidal estrogens during pregnancy.

Cervical erosion has been noted most often, but vaginal adenosis has been proven by biopsy in over 30 percent, and transverse vaginal and cervical ridges have been seen in approximately 10 percent of the exposed population. Although the use of these drugs had been widespread during the last two decades, the Registry of Clear-Cell Adenocarcinoma of the Genital Tract in Young Females has been able to collect only 170 cases of vaginal and cervical cancers of this type from all over the world.

It is important that cytologists and pathologists become familiar with the various non-enoplastic and neoplastic disorders related to these hormones in order that additional epidemiologic, clinical and pathological information be acquired without delay.

Sources: Vaginal and cervical abnormalities, including clear-cell adenocarcinoma, related to prenatal exposure to stilbestrolNCBI, Dr Herbst A, Jul 1974.

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Effect of Estrogen/Androgen Perturbation on Penile Development in DES-treated Mice

DES exposure and male mice genital abnormalities

Analysis of the Effect of Estrogen/Androgen Perturbation on Penile Development in Transgenic and Diethylstilbestrol-Treated Mice
DES exposure and male mice genital abnormalities.

Because both androgens and estrogens have been implicated in penile morphogenesis, we evaluated penile morphology in transgenic mice with known imbalance of androgen and estrogen signaling using scanning electron microscopy (SEM), histology, and immunohistochemistry of androgen and estrogen receptors α/β. Penises of adult wild-type, estrogen receptor-α knockout (αERKO), estrogen receptor-β knockout (βERKO), aromatase knockout (Arom-KO), and aromatase overexpression (Arom+) mice were evaluated, as well as adult mice treated with diethylstilbestrol (DES) from birth to day 10. Adult penises were examined because the adult pattern is the endpoint of development. The urethral orifice is formed by fusion of the MUMP (male urogenital mating protuberance) with the MUMP ridge, which consists of several processes fused to each other and to the MUMP. Similarly, the internal prepuce is completed ventrally by fusion of a ventral cleft. In adult murine penises the stromal processes that form the MUMP ridge are separated from their neighbors by clefts. αERKO, βERKO, and Arom-KO mice have penises with a MUMP ridge clefting pattern similar to that of wild-type mice. In contrast, Arom+ mice and neonatally DES-treated mice exhibit profound malformations of the MUMP, MUMP ridge clefting pattern, and internal prepuce. Abnormalities observed in Arom+ and neonatally DES-treated mice correlate with the expression of estrogen receptor-beta (ERβ) in the affected structures. This study demonstrates that formation of the urethal orifice and internal prepuce is due to fusion of separate epithelial-surfaced mesenchymal elements, a process dependent upon both androgen and estrogen signaling, in which ERβ signaling is strongly implicated.

Read the full articleAnalysis of the Effect of Estrogen/Androgen Perturbation on Penile Development in Transgenic and Diethylstilbestrol-Treated Mice, NCBI, July 2013 – Full PDF.

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Bisphenol-A BPA and the Great Divide

A Review of Controversies in the Endocrine Disruptors Field

Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption
The data collected thus far in the field of environmental toxicology are sufficiently robust to raise concerns about the potentially deleterious impact of endocrine-disrupting chemicals on human development.

In 1991, a group of 21 scientists gathered at the Wingspread Conference Center to discuss evidence of developmental alterations observed in wildlife populations after chemical exposures. There, the term “endocrine disruptor” was agreed upon to describe a class of chemicals including those that act as agonists and antagonists of the estrogen receptors (ERs), androgen receptor, thyroid hormone receptor, and others. This definition has since evolved, and the field has grown to encompass hundreds of chemicals. Despite significant advances in the study of endocrine disruptors, several controversies have sprung up and continue, including the debate over the existence of nonmonotonic dose response curves, the mechanisms of low-dose effects, and the importance of considering critical periods of exposure in experimental design. One chemical found ubiquitously in our environment, bisphenol-A (BPA), has received a tremendous amount of attention from research scientists, government panels, and the popular press.

In their review, The Endocrine Society has covered the above-mentioned controversies plus six additional issues that have divided scientists in the field of BPA research, namely:

  1. mechanisms of BPA action
  2. levels of human exposure
  3. routes of human exposure
  4. pharmacokinetic models of BPA metabolism
  5. effects of BPA on exposed animals
  6. links between BPA and cancer

Understanding these topics is essential for educating the public and medical professionals about potential risks associated with developmental exposure to BPA and other endocrine disruptors, the design of rigorously researched programs using both epidemiological and animal studies, and ultimately the development of a sound public health policy.