Estrogen
Episodes
Dr. Rhonda Patrick explores cheese's health impact, ergothioneine's longevity properties, sleep and joint supplements, and red light therapy in her latest Q&A.
Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
In this clip, Dr. Rhonda Patrick describes the effect of sex hormones on immune function.
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Rhonda Sleep Omega-3 Magnesium MRSA Estrogen Calcium Sauna Saturated Fat Arthritis Berberine Supplements CocoaDr. Rhonda Patrick explores cheese's health impact, ergothioneine's longevity properties, sleep and joint supplements, and red light therapy in her latest Q&A.
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Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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In this clip, Dr. Rhonda Patrick describes the effect of sex hormones on immune function.
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COVID-19 Vitamin D Nutrition Exercise Microbiome Sleep Vitamin C Omega-3 Inflammation Immune System Virus Micronutrients Vitamin E Vaccine Genetics Testosterone Estrogen Zinc Fiber AutoimmunityCOVID-19 Q&A Part 2: Rhonda Patrick, Ph.D. answers subscriber questions in a multi-part series.
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Dr. Ruth Patterson describes how obesity - along with the growth factors estrogen and insulin - affect the risk of breast cancer development and recurrence.
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In this clip, Dr. Ruth Patterson discusses how eating in accordance with the body's natural circadian rhythm may reduce the risk of breast cancer.
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Dr. Elissa Epel identifies some of the key differences in male and female biology and how they influence telomere length and aging.
Topic Pages
News & Publications
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Female sex hormone influences Alzheimer's pathology in mice, with implications for prevention and treatment. www.sciencedaily.com
Alzheimer’s disease disproportionally affects women, who account for nearly two-thirds of all cases worldwide. Some evidence suggests female sex hormones influence the pathology and progression of Alzheimer’s disease. A recent study in mice shows that the brains of male and female mice with Alzheimer’s regulate amyloid-beta protein differently, with the hormone estradiol playing a critical role.
Researchers measured amyloid-beta accumulation in male and female mice when exposed to differing levels of cholinergic tone (acetylcholine release). Then, they examined the effects of removing the ovaries (the primary source of estradiol) and estradiol replacement on this relationship. Finally, using magnetic resonance imaging techniques, they assessed the amyloid-beta burden in the brains of 130 older adults.
They found that acetylcholine activity and the development of amyloid-related issues in male and ovariectomized female mice were directly linked. This link, however, was not observed in female mice with intact ovaries or females without ovaries that received estradiol. They also found that the age-related decline in acetylcholine worsens the amyloid-beta burden in older adults.
Amyloid-beta is a toxic protein that clumps together, forming plaques in the brain – a hallmark of Alzheimer’s disease. Cholinergic neurons are vital for cognition and perception. They release acetylcholine, a neurotransmitter that facilitates impulse firing between neurons. Cholinergic neurons are particularly vulnerable to amyloid-beta’s toxic effects, which impair acetylcholine release. The relationship between acetylcholine and amyloid-beta is bidirectional: amyloid-beta aggregation impairs acetylcholine production, in turn increasing amyloid-beta aggregation, creating a vicious cycle.
These findings suggest that estradiol, a female sex hormone, influences amyloid-beta burden in mice. They also highlight the need for Alzheimer’s research to consider sex differences, the relationship between acetylcholine signaling and amyloid-beta buildup, and the effects of sex hormones to better develop treatment strategies.
Heat shock proteins inhibit amyloid-beta clumping and reduce amyloid-beta plaque toxicity. Sauna use increases heat shock protein production and activity, potentially reducing the risk of Alzheimer’s disease. Learn more in our sauna overview article.
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Pregnancy hormones drive neurological changes in mice, inducing maternal behavior. www.sciencedaily.com
Pregnancy induces marked changes in the female body to prepare for birth, lactation, and the responsibilities of motherhood. A growing body of evidence suggests pregnancy also changes the female brain. A recent study in mice shows that estrogen and progesterone alter galanin-producing neurons in the brain, switching on maternal behavior before offspring arrive.
Researchers analyzed the effects of various pregnancy-related hormones on the brain activity of pregnant mice. Then they blocked the activity of the hormones and assessed the animals' behavior.
They found that estrogen dampened the baseline activity of galanin-expressing neurons in the hypothalamus while increasing their responsiveness. Progesterone reshaped the neurons' connections by driving more synapse formation. Blocking the two hormones' influence in pregnant mice prevented the emergence of maternal behavior, even after giving birth.
Galanin is a neurohormone and neurotransmitter produced in the central nervous system, particularly the hypothalamus. It plays versatile physiological roles in the neuroendocrine axis, such as regulating food intake and insulin levels and driving maternal and fetal weight gain during pregnancy.
These findings suggest that female hormones alter the brain during pregnancy, inducing maternal behaviors and ultimately influencing offspring survival. Learn how maternal health influences offspring health in this clip featuring Dr. Elisa Eppel.
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Growth hormone cuts fracture risk in half for women with osteoporosis. endocrinenews.endocrine.org
Growth hormone improves bone density and reduces the risk of fractures in women with osteoporosis, according to a 2015 study. Women who received growth hormone were half as likely to experience a fracture over a 10-year period than women who did not.
The study involved 80 women (50 to 70 years old) who had osteoporosis and were taking estrogen-based hormone replacement therapy. Researchers randomly assigned the women to receive daily injections of either a low or high dose of growth hormone for three years or a placebo for 18 months. All the women took daily vitamin D and calcium supplements for the study’s duration. The researchers measured the women’s body composition and bone mass at regular intervals.
They found that women who received growth hormone injections showed marked improvements in their bone mineral density and bone mineral content compared to those who received the placebo. Over the 10-year period, the number of fractures among the women who received growth hormone dropped from 56 percent to 28 percent, whereas fractures among those who received the placebo increased from 8 percent to 32 percent.
Growth hormone, a peptide hormone produced in the pineal gland, promotes growth in childhood and adolescence. During middle age, growth hormone production decreases. Some evidence suggests that because growth hormone is secreted at night (during sleep), not getting enough sleep may hinder growth hormone release, exacerbating age-related bone loss. Learn how body temperature can influence how well you sleep at night in this clip featuring Dr. Matthew Walker.
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Plant-based estrogen supplements aren't as effective at maintaining bone health as claimed. www.purdue.edu
Plant-derived estrogen-like compounds found in dietary supplements are not as effective at reducing bone loss as claimed, a 2009 study showed. When compared to conventional therapies such as hormones or anti-osteoporosis drugs, the plant-based treatments were roughly four to five times less effective at reducing bone loss.
Over a period of 50 days, 11 postmenopausal women received six different treatments: soy cotyledon (the first leaves to appear on the plant), soy germ, kudzu (a plant used in traditional and folk medicine), red clover, risedronate (a drug used to treat osteoporosis), and estrogen combined with progesterone. Researchers measured the women’s bone loss after each treatment.
They found that the different treatments reduced bone loss to varying degrees: estrogen combined with progesterone, 24 percent; risedronate, 22 percent; soy cotyledon, 9 percent; soy germ, 5 percent. Red clover and kudzu had only marginal effects on reducing bone loss. Bone loss is a common feature of aging, especially among post-menopausal women.
Estrogen preserves bone health and is commonly prescribed as a treatment for women with osteoporosis. However, estrogen therapies and many common anti-osteoporosis drugs carry health risks. Plant-derived estrogen-like compounds, often referred to as phytoestrogens, are often touted as viable alternatives to conventional therapies.
This study demonstrates that plant-based therapies are less effective at reducing bone loss than hormonal or pharmaceutical therapies. They also underscore the importance of building bone mass in early life. Resistance exercise has been shown to preserve and even increase bone mass in postmenopausal women. Learn more about the effects of resistance training on bone health in this episode featuring Dr. Brad Schoenfeld.
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Common estrogen receptor genotype may double HDL cholesterol increase in response to estrogen therapy in postmenopausal women. (2002) www.sciencedaily.com
From the article:
In an analysis of 309 women with heart disease who took hormone replacement therapy or placebo, Herrington found that women with a common mutation in the estrogen receptor alpha gene had dramatic increases in high-density lipoprotein (HDL), or the “good” cholesterol.
“The increase in HDL was more than twice as much as in women without the gene variant,” said Herrington.
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Herrington found that 18 percent of women had a genetic predisposition to high levels of HDL cholesterol when taking estrogen. The HDL increase was dramatic – it was two or three times what is normally achieved with cholesterol drugs used to raise HDL.
From the publication:
Postmenopausal women with coronary disease who have the ER-α IVS1–401 C/C genotype, or several other closely related genotypes, have an augmented response of HDL cholesterol to hormone-replacement therapy.
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Size of estrogen dose may be critical in determining whether estrogen therapy leads to cardiovascular or kidney disease, mouse study suggests. (2008) www.sciencedaily.com
From the article:
For a 60 day period ovariectomized (OVX) mice received the estrogen hormone 17β—estrodial (E2), a drug very similar to that used in treating the symptoms of menopause. The mice received one of four dosing levels every day throughout the study period: a very low (VL) dose (0.001 µg/d); a low (L) dose (0.42 µg/d); a moderate (M) dose (4.2 µg/d); or a high (H) dose (28.3 µg/d).
The researchers found that:
– Moderate and high doses of ERT increased the plasma estrogen levels in the mice more than four fold (4.5). This was associated with fluid retention in the uterus, amounts of protein in the urine, and dilated kidneys.
– By contrast, low doses of E2 restored plasma estrogen to levels similar to the control rats and neither fluid retention nor renal damage was found in this group of mice.
– Moderate and high doses of E2 also increased atrial natriuretic peptide (ANP), a cardiac hormone that is increased as a marker of severity of heart failure. At low level dosing this did not occur.
– Overall blood pressure and cardiac function were not changed by ERT at any given dose.
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Other factors such as the ratio of estrogen to progestin, the age when the therapy begins and the cardiovascular health_ of the patient when treatment starts may also be important factors to investigate.
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Estrogen plus progestin use may be associated with increased breast cancer incidence, especially when its use is initiated close to menopause. (2013) www.sciencedaily.com
From the article:
The researchers found that breast cancer incidence was higher in estrogen plus progestin users than incidence in nonusers. Women who started hormone therapy closer to menopause had a higher breast cancer risk with a weakening influence as the time from menopause increased.
“Because survival after breast cancer diagnosis did not differ between estrogen plus progestin users and nonusers, the higher breast cancer incidence of those using estrogen plus progestin may lead to increased breast cancer mortality on a population basis,” the authors write.
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“In general, tumors in estrogen plus progestin users in the WHI Observational Study were not significantly different from those in non-hormone users with regard to number of positive lymph nodes or tumor size, but were more likely to be well differentiated and positive for hormone receptors, findings which are similar to other observational studies.” This, however, did not translate into a survival benefit.
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Estrogen therapy may reduce susceptibility and inflammatory responses to urinary tract infections in postmenopausal women, mouse study suggests.(2013) www.sciencedaily.com
From the article:
To simulate menopause in mice, scientists surgically remove their ovaries. Like menopausal women, the mice no longer make estrogen.
To rule out the possibility that the stress of surgery affects the risk of urinary tract infections, the researchers conducted the same surgery in other mice but put the ovaries back in, maintaining their ability to make estrogen.
When researchers gave both groups of mice urinary tract infections, the menopausal mice had higher levels of infectious bacteria in their urine. Most of the bacteria came from barrier cells, which line the interior of the bladder. These cells are the first to be infected by the bacteria.
“When the barrier cells are lost, they need to be replaced immediately,” Mysorekar says. “In the menopausal mice, we found that this replacement process was stopping short of completion. That left cells under barrier cells exposed, and they are much more vulnerable to infection.”
The menopausal mice had more bacterial reservoirs, which are pockets of infection that may provide a place for the bacteria to hide during antibiotic treatment. After treatment stops, the reservoirs can reseed the infection.
In earlier research, Mysorekar had identified an important regulator of the barrier cell repair process. In the new study, she showed that low estrogen levels disable this regulator.
The bladders of the menopausal mice also had higher levels of immune inflammatory compounds known as cytokines.
“The cytokines caused inflammation that left the bladder in bad shape,” Mysorekar says. “It’s possible that damage caused by inflammation increases the bacteria’s ability to break into bladder tissue and create reservoirs of infection.”
In the control mice, which had normal estrogen levels, cytokine levels and inflammatory damage were both significantly lower. When researchers gave the menopausal mice estrogen, their cytokine levels and inflammatory damage also decreased significantly, as did reservoirs of infectious bacteria.
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Taking estradiol may slow progression of atherosclerosis in healthy postmenopausal women. (2001) www.sciencedaily.com
From the article:
Called the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) the study monitored how much artery walls thickened over two years in 222 healthy postmenopausal women who took unopposed estrogen or a placebo.
Women on estrogen therapy saw their atherosclerosis rate decrease by .0017 millimeters (mm) per year over two years, while artery wall thickness increased by .0036 mm per year over two years in women who took a placebo.
As a guideline, Hodis says, an increase of .033 mm per year translates to a two-to-three-fold increase in risk of events such as heart attacks, and a starting thickness of .8 mm or greater also puts an individual at high risk.
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Also, EPAT investigators could compare women who used cholesterol-lowering drugs against women who did not take such medication. Besides taking estrogen or a placebo, all women who started the trial with levels of 160 or higher of low-density lipoprotein (often called LDL or “bad” cholesterol) were put on a cholesterol-lowering medication.
Among the group of women who took no cholesterol-lowering medications in EPAT, those on estrogen therapy had .0147 mm per year slower atherosclerosis progression than those who took a placebo.
Interestingly, women who received both estrogen and cholesterol-lowering drugs had about the same decrease in atherosclerosis progression as women who took cholesterol-lowering drugs alone.
Researchers do not know why the combination of estrogen and cholesterol-lowering drugs does not result in even further atherosclerosis improvement. “But the effects of lipid-lowering drugs are quite powerful,” Hodis says. “You’re probably not seeing any effect above that.”
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Postmenopausal women with colon cancer lived longer and had a 36% lower risk of dying from the disease if they had taken estrogen supplements. (2006) www.sciencedaily.com
From the article:
The research by Chan and her colleagues drew on data from 834 postmenopausal women enrolled in the Nurses' Health Study – which has tracked the health of more than 100,000 female nurses since 1976 – who had been diagnosed with colon cancer between 1976 and 2000. The researchers found that, compared to women who had never used estrogen, those using the hormone at the time of diagnosis had a 36 percent lower chance of dying of colon cancer and a 26 percent lower chance of dying of any cause. The benefit was most pronounced in women who used estrogen for less than five years. Using it for longer, however, did not seem to provide a similar advantage.
The authors do not know why using estrogen for more than five years did not improve women’s chances of survival. They theorize that colon tumors that developed in women who had used estrogen for many years may have been less susceptible to estrogen’s growth-slowing effects.
The precise way by which estrogen foils the growth of colon cancer cells is unclear, as well. The study authors offer three possibilities: the hormone directly suppresses the cells' growth; it decreases the production of bile acids which are known to spur cancer; or it blocks certain genetic changes within colon cells that lead to cancer.
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Postmenopausal women may have lower postprandial fatty acid oxidation, greater meal fatty acid storage, and direct free fatty acid storage. (2013) www.sciencedaily.com
From the article:
Santosa’s research compared fat storage in pre- and post-menopausal women. The 23 women who participated in the study were in the same age range, and had similar Body Mass Indices and body fat composition. These similarities allowed Santosa to isolate the effects of estrogen on fat absorption and storage.
She and Jensen were able to examine the activity of certain enzymes and proteins that regulate fat storage in post-menopausal women’s abdomens and thighs. By considering these factors together rather than in isolation, the researchers determined conclusively that the overall fat storage “machinery” is more active in post-menopausal women. In other words, these cells now store more fat than they did before menopause.
In addition, post-menopausal women burned less fat than their pre-menopausal colleagues. These changes mean that their cells are not only storing more fat, but are also less willing to part with it. This combination is a recipe for rapid weight gain. “Taken together, these changes in bodily processes may be more than a little surprising – and upsetting – for women who previously had little trouble managing their weight,” comments Santosa.
Though the increased cellular activity revealed by this study was not specific to the abdominal region, more fat stored overall means more abdominal fat.
From the publication:
We found that meal FA [fatty acid] storage in subcutaneous fat was greater in postmenopausal than in premenopausal women. This difference was especially evident in the femoral depot, where meal FA [fatty acid] storage in postmenopausal women was double that of premenopausal women.
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The increase in fat storage stems from somewhat greater LPL [lipoprotein lipase] activity and significantly greater content of adipocyte FA [fatty acid] storage factors. It is possible that the upregulation in proteins associated with FA [fatty acid] storage capacity in postmenopausal women contributes to the decrease in postprandial total fat oxidation. Whether the differences in FA [fatty acid] storage between premenopausal and postmenopausal women are attributable to the effects of estrogen or the combination of estrogen, progesterone, and other factors, such as changing insulin concentrations, remains to be elucidated.
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Women who took conjugated equine estrogen had more than twice the risk of developing benign proliferative breast disease. (2008) www.sciencedaily.com
From the article:
In the Women’s Health Initiative study, 10,739 postmenopausal women with hysterectomy were assigned to either conjugated equine estrogen or a placebo. Previous analyses did not show an increase in breast cancer incidence in the women who took estrogen alone after a median follow-up of seven years.
To determine whether the hormone increases the risk of benign proliferative breast disease [condition that is associated with increased risk of breast cancer], Tom Rohan, M.D., Ph.D., of the Albert Einstein College of Medicine in New York and colleagues identified and examined non-cancerous breast biopsies in each of the Women’s Health Initiative trial arms.
A total of 232 cases of benign proliferative breast disease were identified, with 155 cases among the women who took estrogen supplements and 77 in the placebo group. The risk of developing benign disease increased by more than two-fold for women taking conjugated equine estrogen, compared with those taking a placebo.
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Although the women taking conjugated equine estrogen have not yet shown a significant increased risk of breast cancer in the Women’s Health Initiative study, if this hypothesis holds true, they might show increased risk later. Ongoing follow up of the study participants may help to resolve this issue.
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Local overproduction of the estrogen-producing enzyme aromatase may push breast cancer development more than estrogen receptor overproduction. (2011) www.sciencedaily.com
From the article:
That means they inserted a gene into mice that expresses human aromatase in the animal’s mammary tissue – a gene the researchers can turn on or off.
They compared this new mouse model to one they had developed several years ago – a conditional mouse model in which a gene that produces estrogen receptors (ER) could also be turned on and off.
While they study found that both mouse models experienced the earliest stages of tumor formation, known as preneoplasia, the aromatase over-expressing mice model exhibited both increased preneoplasia and outright development of cancer. These mice also expressed proteins that are tightly linked to cancer, Furth says.
The researchers also found, to their surprise, that aromatase over-expressing mice expressed more estrogen receptors than did the ER-conditional mice. “Increased aromatase produced both more estrogen and the receptors that the hormone needs to enter breast cells,” says Díaz-Cruz. “This is obviously a greater risk for development of breast cancer than just over-expression of estrogen receptors.”
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These mice also over-expressed progesterone receptors, downstream targets of estrogen receptors that can be cancer-promoting in some settings, as shown in this study in the context of aromatase over-expression.
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Finally, they tested the effect of local versus systemic estrogen on development of preneoplasia. The researchers made three comparisons: between mice in which the ER was over-expressed; mice that had excess estrogen due to aromatase; and mice that were given more estrogen systemically. “If we give extra systemic estrogen, we don’t see any increased risk of breast cancer, but the risk increases with extra expression of ER, and is higher still with local production of aromatase,” says Díaz-Cruz. “That suggests that estrogen production in the breast is an important risk factor for development of breast cancer.”
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Quinol-based antioxidant cycle may maintain the "chemical shield" raised by estrogens that protects neurons from reactive oxygen species. (2003) www.sciencedaily.com
From the article:
“We now know how estrogen keeps brain cells alive even when exposed to an insult like stroke, Alzheimer’s disease or Parkinson’s disease.”
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“During a stroke, free radicals damage important cells in the body, most notably nerve cells,” said Laszlo Prokai, PhD, a chemist with UF’s College of Pharmacy.
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“In layman’s terms, a spill occurs when the blood starts flowing into the blocked territory, and the overflow hydroxyl radical is the spill,” Prokai said. “The estrogen is the mop, soaking up the hydroxyl radicals before they do damage. But when the mop is saturated, you have to squeeze it to continue mopping. This mechanism has never been fully understood before.”
When the estrogen and hydroxyl radicals combine, an unusual molecule called a quinol is produced. In this form, the hydroxyl radicals are harmless, but the estrogen is no longer useful as an antioxidant. Prokai investigated and discovered chemicals in the body transform the quinol back to estrogen, effectively wringing out the mop and making it useful again.
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In terms of therapies, scientists believe administering the quinol — the saturated mop — will deliver the protective benefits of estrogen, because the body will naturally wring it out and convert it to estrogen, while side effects associated with direct estrogen therapy, such as feminization in men, may remain in check.
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Estrogen may help lower LDL cholesterol levels in the blood by inhibiting the protein PCSK-9. (2014) www.sciencedaily.com
From the article:
Dr. Ross Feldman, a clinical pharmacologist at London Health Sciences Centre and a scientist at the Schulich School of Medicine & Dentistry’s Robarts Research Institute, and his colleagues showed that the G-protein coupled estrogen receptor 30 (GPER) when activated by estrogen helps lower LDL cholesterol levels in the blood by inhibiting the protein PCSK-9.
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The study, which looked at two populations of women in northern Alberta and London, Ontario, also found that women who carry a common gene variant for GPER have a significant increase in LDL cholesterol levels. The gene variant, found in about 20 per cent of the population, impairs the ability of GPER to function and was shown in a previous study by the same authors to be associated with significant increases in blood pressure in women.
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Commercial phytoestrogen supplements containing genistein-like soy isoflavones significantly reduced bone loss by up to 9%. (2009) www.sciencedaily.com
Plant-based estrogen supplements aren’t as effective at maintaining bone health as claimed.
Plant-derived estrogen-like compounds found in dietary supplements are not as effective at reducing bone loss as claimed, a 2009 study showed. When compared to conventional therapies such as hormones or anti-osteoporosis drugs, the plant-based treatments were roughly four to five times less effective at reducing bone loss.
Over a period of 50 days, 11 postmenopausal women received six different treatments: soy cotyledon (the first leaves to appear on the plant), soy germ, kudzu (a plant used in traditional and folk medicine), red clover, risedronate (a drug used to treat osteoporosis), and estrogen combined with progesterone. Researchers measured the women’s bone loss after each treatment.
They found that the different treatments reduced bone loss to varying degrees: estrogen combined with progesterone, 24 percent; risedronate, 22 percent; soy cotyledon, 9 percent; soy germ, 5 percent. Red clover and kudzu had only marginal effects on reducing bone loss. Bone loss is a common feature of aging, especially among post-menopausal women.
Estrogen preserves bone health and is commonly prescribed as a treatment for women with osteoporosis. However, estrogen therapies and many common anti-osteoporosis drugs carry health risks. Plant-derived estrogen-like compounds, often referred to as phytoestrogens, are often touted as viable alternatives to conventional therapies.
This study demonstrates that plant-based therapies are less effective at reducing bone loss than hormonal or pharmaceutical therapies. They also underscore the importance of building bone mass in early life. Resistance exercise has been shown to preserve and even increase bone mass in postmenopausal women. Learn more about the effects of resistance training on bone health in this episode featuring Dr. Brad Schoenfeld.
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Oral, but not topical, estrogen therapy for menopausal women may be associated with an increased risk of complicated gallstone disease. (2013) www.sciencedaily.com
From the article:
A large study of 70 928 menopausal women in France between 1992 and 2008 looked at whether hormone therapy increased the risk of gallbladder surgery (cholecystectomy) for complications of gallstones. In France, hormonal therapy is usually administered topically rather than orally. North America and the United Kingdom prefer oral hormone therapies.
“In this large French prospective cohort study, we found that the risk of cholecystectomy was increased among women exposed to oral estrogen regiments for menopausal hormone therapy, especially oral regimens without progestagen,” writes Dr. Antoine Racine, Institut national de la santé et de la recherche médicale (INSERM) and Université Paris Sud, with coauthors. “Other types of menopausal hormone therapy [skin patches or gels] were not associated with an increased risk of cholecystectomy.”
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Estrogen receptor beta activation in spinal cord neurons may modulate pain sensitivity and may be important for pain and sensation transmission.(2007) www.sciencedaily.com
From the article:
Earlier studies have shown that estrogen affects how we experience pain, but the mechanisms behind this have been unclear. Estrogen can bind to two different receptors, known as ER-alpha and ER-beta, and the new study describes results obtained concerning the expression of these two receptors in the spinal cord.
The results show that ER-beta plays an important role in the development of the part of the spinal cord that contains nerve fibres that carry information to the brain. These nerves are important in several functions, including determining how sensitive a person is to pain, and response to sensation in general. ER-beta is the dominant estrogen receptor during the development of the embryo. The researchers also showed that neuronal development occurs later in mice that lack ER-beta, and that ER-beta is important in the spinal cord of the adult animal for the survival of nerve cells and for the transmission of pain and sensation.
“These results are particularly interesting in the light of preliminary results from pre-clinical studies that suggest that substances that stimulate ER-beta can give pain relief”, says Jan-Åke Gustafsson.
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Estrogen fluctuations may trigger atypical hippocampal working memory function in women with a BDNF genotype present in one in four women. (2017) www.sciencedaily.com
From the article:
The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that codes for BDNF [Val66Met genotype] (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.
The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain’s memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.
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Estrogen therapy was less memory-enhancing in mice raised in a stimulating environment than in mice raised in non-stimulating environments. (2004) www.sciencedaily.com
From the article:
“We saw no beneficial effect of estrogen in the animals in cognitively and physically stimulating environments (also known as enriched environments),” said Karyn Frick, assistant professor of psychology and principal investigator on the study. “This fits in nicely with human data and might help to explain why studies of hormone replacement therapy (HRT) do not show beneficial effects for all women. Most studies of HRT use very well-educated women. These results might spur researchers to include a broader population with a greater variation in education and socioeconomic status.”
[…]
“Animals [that had their ovaries removed to simulate menopause] raised in standard conditions showed significant spatial and object memory improvement when treated with a high dose of estrogen, whereas memory in animals in the enriched environment were unaffected or impaired by estrogen treatment,” Frick said. “Among mice not treated with estrogen, enrichment treatment alone significantly improved spatial memory. The behavioral changes were also associated with alterations in a part of the brain critical for memory. These data suggest that estrogen benefits mice raised in un-stimulating environments more than those raised in cognitively and physically stimulating environments.”
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Improved hippocampal estrogen reception sharpened spatial learning in estrogen receptor-α knockout mice with low estrogen levels. (2008) www.sciencedaily.com
From the article:
Changes in the estrogen receptor have been associated with age-related memory deficits and an increased incidence of Alzheimer’s disease among women In addition, previous studies have shown estrogen replacement may improve cognition in postmenopausal women and younger women with low estrogen levels. Estrogen also appears to protect against Alzheimer’s disease and dementia.
[…]
The mice had unusually low levels of estrogen because their ovaries were removed at an early age. However, scientists were still able to rescue learning ability by delivering the correct gene to produce estrogen receptor-alpha directly to the hippocampus.
Mice that lacked the estrogen receptor showed poor ability to locate a platform hidden in a small swimming tank over a training period of several days. After receiving the gene, the mice learned to locate the platform in two days of training.
[…]
Recordings made from the brain tissue of treated mice showed signals were strongly communicated across the gaps, or synapses, between hippocampal cells, similar to what would happen with estrogen replacement.
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In young female athletes with exercise-induced amenorrhea, estrogen replacement may improve their verbal memory and cognitive flexibility. (2016) www.sciencedaily.com
From the article:
Study participants were randomly assigned to one of three treatment groups for six months: (1) oral estradiol and progesterone at a dose similar to that in many birth control pills (16 participants); (2) transdermal estradiol, better known as the estrogen patch, at a physiological replacement dose with cyclic progesterone (13 athletes); or (3) no estrogen (19 subjects). Participants who received estrogen therapy also received progesterone because giving estrogen alone can increase the long-term risk of uterine cancer, Baskaran noted.
[…]
Compared with those who received no hormone treatment, athletes in the two estrogen treatment groups taken together had significantly better verbal memory and cognitive flexibility scores at the end of six months than their pre-treatment scores, the investigators reported. The estrogen recipients had greater improvement in both immediate recall of words and in their ability to flexibly switch back and forth between tasks, even when the researchers controlled for patient age and pre-treatment test scores.
When the researchers evaluated the estrogen treated groups separately versus no treatment, they found significantly greater improvement in certain cognitive tests only in the group that received transdermal estrogen.
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Estrogen may reduce high-fat diet-induced visceral fat accumulation by decreasing the expression of a vitamin A-converting enzyme - mouse study.(2012) www.sciencedaily.com
From the article:
The hormonal effect seen in these mice relates at least in part to how the female body processes vitamin A, a nutrient that is converted into a variety of compounds. These include a molecule that supports the burning of fat for energy, as well as retinoic acid, the hormone in this study that leads to the formation of visceral fat. The scientists showed that a high-fat diet functions as a switching mechanism that breaks down the fat-burning molecule and leads to activation of the enzyme and production of retinoic acid, ending in the development of visceral fat.
A year ago, Ziouzenkova’s lab identified the one of these enzymes that relates to fat accumulation: Aldehyde Dehydrogenase 1, or Aldh1a1. In the current study, she and colleagues conducted numerous experiments in mice to track the events that followed activation of this enzyme.
The researchers compared normal mice with genetically altered mice lacking the enzyme over almost a year of eating a high-fat diet. Male and female normal mice gained weight on the high-fat diet, as expected, though the females developed more visceral fat that surrounds the organs than did males, a trend also seen in humans as the result of eating excess fat. (In contrast, on a regular diet, men are more likely than women to form abdominal fat.) Both sexes of mice developed peripheral subcutaneous fat, which lies just under the skin and has some benefits.
In mice without the enzyme, however, the males developed some fat but females remained lean, and this occurred even when females ate more food than males. The researchers determined that without Aldh1a1, the females were not producing retinoic acid, and that protected them from producing visceral fat. Meanwhile, males retained the ability to produce retinoic acid.
The scientists then analyzed the proteins contained in fat tissue in male and female mice lacking the enzyme, and saw that only the females' fat cells contained high levels of a protein that releases fat from fat cells to support fat burning. This release led to production of another protein that converts fat to heat, essentially burning the fat, in the form of lipids, away.
“Without production of the hormone retinoic acid, females are burning fat and expending the energy in the form of heat. That’s why they stay very lean,” Ziouzenkova said. “And this process was specifically affecting visceral fat.”
The researchers surgically removed the ovaries of mice to test whether estrogen could be related to visceral fat production in females. As soon as the animals became menopausal and weren’t producing estrogen, they began to produce retinoic acid, which led to visceral fat formation.
“Estrogen was sufficient to protect female mice from both hormonal and, partially, diet-induced obesity. This means estrogen is suppressing activation of the obesity-inducing hormone, and as soon as we lose this estrogen during menopause, the visceral fat starts to grow,” said Ziouzenkova, also an investigator in Ohio State’s Comprehensive Cancer Center.
Using another mouse model that allowed researchers to measure hormone production specifically, the researchers observed that female mice on a regular diet barely produced retinoic acid. However, females on a high-fat diet produced high levels of the hormone and, in turn, showed a nine-fold increase in visceral fat compared to visceral fat developed by males on a high-fat diet. This was the final determinant that the high-fat diet triggers this cascade of events ending in visceral fat formation.
Because the human fat tissue samples the researchers analyzed also showed elevated levels of Aldh1a1 in cells extracted from tissue in obese women, “it could be that what we show about this hormone’s importance to visceral obesity in mice is also true for humans,” Ziouzenkova said.
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Long-term estrogen treatment reduced androgen levels in female monkeys by up to 53% and increased cortisol levels. (2004) www.sciencedaily.com
From the article:
“Our findings suggest that it might be important for women taking estrogen after menopause to also take androgen supplements – which can include testosterone,”
[…]
Half of the monkeys were given oral contraceptives, which contain estrogen, in their diets for 26 months. All animals then had their ovaries removed to make them menopausal.
For the next three years, the animals were divided into three groups based on diet. One group ate soy that didn’t contain isoflavones, which are natural plant estrogens; one group ate soy with the isoflavones intact, and one group’s diet was soy without isoflavones and Premarin [conjugated estrogen], or estrogen therapy, added.
[…]
The researchers measured levels of the major androgens, which include dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A4), and testosterone. Monkeys who took the oral contraceptives before menopause had DHEA-S levels that were 27 percent lower than the monkeys who didn’t take contraceptives. Levels of A4 were 53 percent lower, and levels of testosterone were 50 percent lower. These effects did not continue into menopause.
In the postmenopausal phase of the study, treatment with soy plus Premarin resulted in DHEA-S levels that were 29 percent lower than the monkeys who ate soy without isoflavones (control group) and 35 percent lower than the group eating soy with isoflavones. Total levels of testosterone were 52 percent lower than the control group and 41 percent lower than the group eating soy with isoflavones.
The researchers had suspected that the plant estrogens would also suppress androgen production. While this didn’t prove true, they did find that these monkeys had smaller adrenal glands than monkeys that didn’t consume the isoflavones.
The adrenal gland, located near the kidneys, uses cholesterol to make the androgen hormones and to make cortisol, a hormone associated with high levels of stress. The researchers found that while estrogen treatment lowered levels of androgen hormones, levels of cortisol increased.
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Estrogen may protect against cocaine-induced brain dysfunction by improving brain blood flow - progesterone and testosterone may be detrimental.(2001) www.sciencedaily.com
From the article:
Lead researcher Marc Kaufman and his colleagues first established the rate of blood flow to the brain in male and female occasional cocaine users. An intravenous dose of cocaine (0.4 mg/kg) was administered to nine men and 13 women. Men were studied once while women were examined during different phases of their menstrual cycle phases (days 3-8, follicular phase and 18-24, leutial phase) after the beginning of menstruation.
[…]
In the follicular phase, when estrogen levels are high and progesterone levels are low, cocaine did not alter the amount of blood in the brain. By contrast, a 10 percent reduction in blood was found in women during their luteal menstrual cycle phase, when progesterone levels rise; male subjects incurred a 20 percent loss. These findings suggest that cocaine’s effects on blood vessels in the brain differ as a function of sex and menstrual cycle phase, and imply that progesterone in women and testosterone in men may enhance cocaine-induced vasoconstriction, while estrogen in women may blunt cocaine’s vascular effects.
[…]
Such benefits could extend beyond drug using populations. For example, treatments that improve brain blood flow might also benefit the elderly, many of whom experience reductions of blood flow to the brain as a result of aging.
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Physiologic estrogen replacement increased bone density in adolescent girls with anorexia nervosa. (2011) www.sciencedaily.com
From the article:
“Previous studies have shown that giving oral estrogen combined with progesterone as birth control pills is not effective in increasing bone density in girls with anorexia nervosa,” Misra said. “However, the impact of giving estrogen in a more natural, or physiological, form has not been previously studied in girls with anorexia nervosa.”
This National Institutes of Health-funded study explored, over an 18-month period, the effect of physiological estrogen replacement on bone accrual rates in 110 female patients with anorexia nervosa. These patients and 40 healthy-weight girls as controls were between ages 12 to 18 years, a common time for anorexia nervosa to start and also an important time for building optimal bone mass, Misra said.
[…] Those girls with mature bone received either placebo or a full adult dose of estrogen (100 micrograms of estradiol) given via a skin patch. This transdermal form is a natural form of estrogen, Misra said. Girls receiving estrogen also received cyclic progesterone pills to reduce the risk of endometrial cancer.
Girls with anorexia nervosa whose bones were immature received incremental low doses of oral estrogen, ranging from 3.75 to 11.25 micrograms of estradiol. These low, natural levels mimic estrogen levels seen in early puberty and avoid accelerating fusion of the growth plates, which would otherwise limit height potential, Misra said. Healthy-weight controls received no treatment other than calcium and vitamin D supplements, which all subjects received.
Using dual-energy X-ray absorptiometry (DEXA) bone density scans, the researchers assessed bone mineral density at the lumbar spine (lower back), hip and whole body. Physiological estrogen administration caused a significant increase in bone density at the spine and hip, compared with placebo, as found on DEXA Z-scores, the authors reported. However, Misra said that estrogen did not result in a complete “catch-up” to normal bone density measures. Girls with anorexia nervosa still had lower bone density than healthy-weight controls did.
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Uterine cells of mice produce their own estrogen during pregnancy, which is critical for maintaining the growth of blood vessels.(2009) www.sciencedaily.com
From the article:
The researchers discovered that during decidualization, mouse uterine stromal cells increase their expression of P450 aromatase, a key enzyme that acts with other enzymes to convert androgens to estrogen.
Even in pregnant mice that have had their ovaries removed, the production of uterine estrogen is able to support the growth and differentiation of the tissue and blood vessels needed to sustain the pregnancy.
Progesterone supplementation is required, however, indicating that local estrogen alone is not sufficient to maintain pregnancy. Blocking the activity of the aromatase with an inhibitor also blocked decidualization, the researchers found, another indication that a successful pregnancy relies on estrogen production in uterine cells.
There are advantages to producing the appropriate amount of estrogen right where it is needed, rather than relying on the ovaries, Bagchi said.
“During pregnancy, the ovaries would need to secrete a high level of estrogen to ensure that the right amount of estrogen is present in the uterus to support decidualization,” she said. “You can imagine that if the estrogen level goes high systemically, it could have a deleterious effect on pregnancy itself by antagonizing the progesterone action.”
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Raising estrogen levels benefited 30% of women whose metastatic breast cancer no longer responded to standard anti-estrogen treatment. (2009) www.sciencedaily.com
From the article:
Sixty-six postmenopausal women with breast cancer that had spread beyond the breast participated in the study. All participants were originally diagnosed with estrogen receptor positive (ER ) breast tumors, meaning estrogen stimulated tumor growth. Seventy-five percent of breast cancer cases are ER . All participants had received aromatase inhibitor treatment, which severely lowers estrogen levels, but their metastatic tumors had later reappeared or resumed growing.
The study compared a high 30-milligram daily dose of estrogen to a low 6-milligram daily dose, and evaluated how well the treatments controlled the women’s metastatic cancers and how the treatments affected their quality of life. The high dose results in estrogen levels in the blood comparable to that of pregnant women, while the low dose gives estrogen levels similar to that of women who are ovulating, Ellis indicates.
In both the high- and low-dose groups about 30 percent of participants experienced a clinical benefit — their tumors either shrank or stopped growing. Interestingly, the researchers demonstrated that they could predict fairly accurately which patients would have this positive response. They conducted standard positron emission tomography (PET) scans before estrogen treatment and 24 hours later. If metastatic tumors flared, or glowed more brightly, in the PET scans after estrogen was started, they were much more likely to be affected by estrogen therapy. In 80 percent of women with PET flare reactions, tumors responded to estrogen therapy, and in 87 percent of women without PET flares, tumors did not respond to estrogen.
[…]
“The older women in the study were, the fewer estrogen-related symptoms they had,” says Ellis also professor of medicine in the Division of Oncology. “But overall, we demonstrated clearly that the low dose was better tolerated than the high dose and was just as effective for controlling metastatic diseas.”
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Estrogen may improve memory and promote neuron repair and function, while progesterone alone may adversely affect memory, rodent studies suggest(2004) www.sciencedaily.com
From the article:
Cyclic administration of estrogen might be inferior to continuous or no administration in terms of improving memory functions.
Researchers removed the ovaries of 32 middle-aged mice before starting them on various courses of HT lasting three months. A continuous group received estrogen injections daily, a cyclical group was administered estrogen every four days, and a control group received daily injections with no estrogen.
After three months, the mice underwent a variety of cognitive tests. […] Mice were tested every day for two weeks for both spatial reference memory (long-term memory for information that did not change during the test session) and working memory (short-term memory for information that changed in each trial).
Mice on the cyclical regimen made more reference and working memory errors than control mice. The cyclical group also made more reference memory errors than mice receiving continuous estrogen.
Another test focused on object recognition, a type of nonspatial memory. […] Because mice have a natural tendency to explore novel objects, mice with good memory for the original objects should spend more time examining the new object. Again, mice in the control and continuous groups outperformed the cyclical HT mice.
Estrogen may promote neuron repair and improve neuronal function.
Other researchers studied the effects of continuous versus no administration of HT. Investigators removed the ovaries of mice aged 8 to 12 weeks and either treated them with continuous estrogen for 47 days or did not treat them with estrogen. Researchers then sacrificed the mice at different time periods after estrogen exposure (at 5, 14, 28, and 47 day intervals) and examined them for the production of the proteins associated with neuron repair and the formation of contacts between neurons.
[…]
After five days on estrogen, the estrogen-treated mice produced more of the proteins important for repair and neuronal function. However, with prolonged, continuous estrogen treatment, this effect diminished, and by day 47 the estrogen-treated mice were similar to the non-estrogen-treated mice in levels of the repair proteins. In addition, at the end of the experiment, mice that did not receive estrogen showed an elevation of a brain protein associated with the negative aspects of brain aging, while estrogen-treated mice did not.
Progesterone may be detrimental to learning and increase short-term memory deficits in aged rats.
Thirty rats were used in the study. Ten rats kept their ovaries, and twenty rats had their ovaries removed. The ovariectomized rats were then divided into two groups: those receiving progesterone and a control group that did not receive progesterone.
As in the Yale study, a water maze was used to test working and reference memory. The maze difficulty was changed at increasing rates, forcing the rats to remember greater amounts of information. The rats receiving progesterone exhibited deficiencies in learning and remembering the maze. In addition, rats treated with progesterone also showed problems remembering many items of information, while untreated rats were able to successfully remember the items.
Progesterone may inhibit neuroprotective effects of estrogen
In the first experiment, levels of beta-amyloid protein were evaluated after a six-week period of hormone treatment. Higher levels of beta-amyloid protein were observed in the hormone-depleted rats compared with control animals. The group receiving estrogen did not experience an increase in levels of beta-amyloid. For the rats receiving the combination of estrogen and progesterone, although progesterone failed to decrease beta-amyloid levels, it did not alter the ability of the estrogen treatment to reduce beta-amyloid levels.
In the second study, rats were treated with a mild dose of neurotoxin after two weeks of hormone treatment. The hormone-depleted rats experienced the greatest amount of neuronal death. In estrogen-treated rats a protective effective against neuronal death was observed, while rats treated with estrogen and progesterone in combination did exhibit neuronal death, suggesting that progesterone inhibited the neuroprotective action of estrogen in this model.
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Loss of estrogen receptor alpha led to aspects of metabolic syndrome, inflammation, and acceleration of atherosclerosis in mice. (2011) www.sciencedaily.com
From the article:
This early preclinical study in female mice demonstrated that removing estrogen regulator alpha alone was enough to reduce the immune system’s protective process and promote increased fat accumulation and accelerate atherosclerosis development. Without this protein, the mice developed additional aspects of metabolic syndrome such as glucose intolerance, insulin resistance and inflammation.
This estrogen receptor is also expressed in many other non-reproductive tissues such as fat, muscle and liver and can also act independent of the hormone estrogen. However, little is known about the receptor’s actions in these tissues that are involved in blood-sugar regulation, which plays an integral role in metabolic syndrome.
[…]
“Impairment of this receptor’s function could also play a role in the heightened incidence of metabolic syndrome being seen in younger women,”
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Estrogen and other sex hormones may be responsible for the higher prevalence of migraine in women, while testosterone may be protective. (2018) www.sciencedaily.com
From the article:
Ferrer-Montiel and his team reviewed decades of literature on sex hormones, migraine sensitivity and cells' responses to migraine triggers to identify the role of specific hormones. Some (like testosterone) seem to protect against migraines, while others (like prolactin) appear to make migraines worse. They do this by making the cells' ion channels, which control the cells' reactions to outside stimuli, more or less vulnerable to migraine triggers.
Some hormones need much more research to determine their role. However, estrogen stands out as a key candidate for understanding migraine occurrence. It was first identified as a factor by the greater prevalence of migraine in menstruating women and the association of some types of migraine with period-related changes in hormone levels. The research team’s evidence now suggests that estrogen and changes in estrogen levels sensitize cells around the trigeminal nerve to stimuli. That makes it easier to trigger a migraine attack.
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Menopausal estrogen loss may be associated with lumbar disc degeneration and back pain, but hormone therapy may be beneficial for disc height. (2017) www.sciencedaily.com
From the article:
Available evidence strongly supports the involvement of estrogen deficiency in disc degeneration, as well as the benefits of hormone therapy (HT) on the total lumbar disc height in postmenopausal women. Multiple studies have previously investigated the association between menopause and lumbar disc degeneration; however, the study detailed in the article “Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men” is the first known to include a portion of age-matched men as a comparison group.
Study results document how men and women fare with regard to disc degeneration, as measured by magnetic resonance imaging, as they age. Whereas young, age-matched men were more susceptible to disc degeneration than premenopausal women were, postmenopausal women had a significant tendency to develop more severe disc degeneration than age-matched men compared with premenopausal and perimenopausal women. The most dramatic difference was seen in the first 15 years after menopause onset, although the authors note that further studies are needed to determine whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.
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Pubertal activation of estrogen receptor α in the medial amygdala is essential for the full expression of male social behavior in mice. (2016) www.sciencedaily.com
From the article:
Behavioral responses to sexually receptive females such as mounting, and toward intruder males such as biting and attacks, were recorded in adult mice. The reduction of both sexual and aggressive behavior by ERα [estrogen receptor alpha] silencing in the MeA [medial amygdala] before puberty but not in adults suggests the importance of the receptor in this location during puberty. “ERα knockdown in the MeA may even have affected the onset of puberty itself,” first author Dr. Kazuhiro Sano says. “This contrasts with the silencing of ERα in the MPOA [medial preoptic area], which reduced sexual but not aggressive behavior in mice, regardless of the time of knockdown treatment.” These findings suggest that ERα gene expression in the MPOA does not control male aggression through either the organizational role of testosterone at puberty, or its regulatory role in adulthood.
To understand why ERα silencing in different areas of the brain had varying effects, the team examined MeA cells. They found that neuronal cells were greatly reduced in MeA in which ERα expression had been inhibited before puberty. “ERα in the MeA seems to be necessary for testosterone to masculinize the neural circuitry for social behavior during puberty,” corresponding author Dr. Sonoko Ogawa explains. “If this masculinization is incomplete, social signals that enable adults to express male social behavior may not function correctly.”
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Memory-enhancing effects of hippocampal estrogen receptor activation involve metabotropic glutamate receptor signaling, mouse study suggests. (2013) www.sciencedaily.com
From the article:
The research, published in the the Journal of Neuroscience today, focused on estrogen effects in a brain region called the hippocampus, which deteriorates with age or Alzheimer’s disease. The researchers found that each of the two known estrogen receptors rapidly activate a specific cellular pathway necessary for memory formation in the hippocampus of female mice, but only if they interact with a certain glutamate receptor, called mGluR1.
The study revealed that when this glutamate receptor is blocked, the cell-signaling protein ERK cannot be activated by the potent estrogen, 17β-estradiol. Because ERK activation is necessary for memory formation, estradiol failed to enhance memory among mice in which mGluR1 was blocked.
Frick’s team also found evidence that estrogen receptors and mGluR1 physically interact at the cell membrane, allowing estradiol to influence memory formation within seconds to minutes.
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Silencing of estrogen receptor α in a brain area of the hypothalamus led to metabolic syndrome in mice. (2007) www.sciencedaily.com
From the article:
Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.
To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.
Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.
When estrogen levels in the VMN dipped, the animals' metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.
The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.
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Estradiol may heighten the sensitivity of sound-processing neurons and activate genes that instruct the brain to lay down memories of sounds. (2009) www.sciencedaily.com
From the article:
Previous studies have hinted at a connection between estrogen and hearing in women who have low estrogen, such as often occurs after menopause, says Pinaud. No one understood, however, that estrogen was playing such a direct role in determining auditory functions in the brain, he says. “Now it is clear that estrogen is a key molecule carrying brain signals, and that the right balance of hormone levels in men and women is important for reasons beyond its role as a sex hormone,” says Pinaud.
Pinaud, along with Liisa Tremere, a research assistant professor of brain and cognitive sciences, and Jin Jeong, a postdoctoral fellow in Pinaud’s laboratory, demonstrated that increasing estrogen levels in brain regions that process auditory information caused heightened sensitivity of sound-processing neurons, which encoded more complex and subtle features of the sound stimulus. Perhaps more surprising, says Pinaud, is that by blocking either the actions of estrogen directly, or preventing brain cells from producing estrogen within auditory centers, the signaling that is necessary for the brain to process sounds essentially shuts down. Pinaud’s team also shows that estrogen is required to activate genes that instruct the brain to lay down memories of those sounds.
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The risk of developing ovarian cancer increased by 220% in postmenopausal women who used estrogen therapy for 20 or more years. (2002) www.sciencedaily.com
From the article:
The scientists followed 44,241 women for approximately 20 years. Compared to postmenopausal women not using hormone replacement therapy, users of estrogen-only therapy had a 60 percent greater risk of developing ovarian cancer. The risk increased with length of estrogen use. The women, who were followed from 1979 to 1998, were former participants in the Breast Cancer Detection Demonstration Project, a mammography screening program conducted between 1973 and 1980.
“The main finding of our study was that postmenopausal women who used estrogen replacement therapy for 10 or more years were at significantly higher risk of developing ovarian cancer than women who never used hormone replacement therapy,” said James V. Lacey, Jr., Ph.D., lead author of the study from NCI’s Division of Cancer Epidemiology and Genetics.
The relative risk for 10 to 19 years of use was 1.8, which translates to an 80 percent higher risk than non-users, and increased to 3.2 (a 220 percent higher risk than non-users) for women who took estrogen for 20 or more years.
[…]
Two recent large studies found a link between hormone use and ovarian cancer. A large prospective study published last year (JAMA 2001;285:1460-1465) showed that postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality, and a recent Swedish study (J. Natl. Cancer Inst. 2002;94:497-504) reported that estrogen use alone and estrogen-progestin used sequentially (progestin used on average 10 days/month) may be associated with an increased risk for ovarian cancer. In contrast, estrogen-progestin used continuously (progestin used on average 28 days/month) seemed to confer no increased ovarian cancer risk.
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During 3rd trimester of pregnancy, multiple sclerosis relapse rate is reduced by 70%, possibly due to the neuroprotective effects of estrogen. (2017) www.sciencedaily.com
From the article:
The third trimester of pregnancy has been previously shown to reduce relapse rates by approximately 70 percent as compared to before pregnancy, and other studies have shown benefit over the long term due to multiple pregnancies. An estrogen unique to pregnancy that is made by the fetus and placenta has been proposed by Dr. Rhonda Voskuhl and colleagues to mediate this pregnancy protection in both the MS mouse model as well as in two successfully completed clinical trials of estriol treatment in MS patients.
How that happens has remained a critical question. Voskuhl, who led the latest study, reported mouse studies showing that estrogen protected the brain from damage by activating a protein called estrogen receptor beta (ERb). Her new research identifies which cells within the brain are mediating this protective effect.
The researchers first genetically eliminated ERb in either immune cells of the brain or in oligodendrocytes, the cells that make the myelin sheath, as a way of making cells unresponsive to estrogen during the MS like disease in mice. They then treated mice without or with ERb in these cells to ask if disease protection was lost or not. Loss of protection during treatment meant that the treatment was acting on the cell that had the receptor removed. Results showed that the estrogen-like treatment was acting on both immune cells of the brain as well as on oligodendrocytes, together resulting in repair of myelin and less disability.
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Chronic estradiol exposure led to hypertension in rats by promoting excessive superoxide levels in a blood pressure regulating brain area. (2011) www.sciencedaily.com
From the article:
The researchers looked to the rostral ventrolateral medulla (RVLM), a critical region in the brain stem known to be involved with the maintenance of blood pressure and thought to be associated with hypertension and heart failure. They theorized that chronic exposure to low levels of estrogen (in the form of estradiol-17β, also called E2) could influence this area of the brain.
[…]
To test their hypotheses they conducted a two-phase experiment using rats. In phase 1, animals were divided into groups and used as either controls or implanted with E2. After 90 days of E2 exposure the animals were examined and key data collected. In phase 2, the animals were used as either controls or implanted with E2 and, in addition, fed resveratrol-laced chow for 90 days. As with phase 1, RVLM was subsequently isolated from each animal and examined for increases in superoxide, hypertension and other key health markers.
Results
The researchers found that chronic E2 exposure caused a significant increase in superoxide in the RVLM, and in blood pressure. In addition they determined that the increases in both indicators were reversed with resveratrol. Taken together, the findings demonstrate that chronic exposure to low levels of E2 is capable of causing hypertension, possibly by increasing superoxide generation in the RVLM.
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Estradiol given to women with mild to moderate Alzheimer's disease improved their memory by up to 35% and attention skills by 20%. (2001) www.sciencedaily.com
From the article:
Asthana noted differences between the current study and those that found no memory-enhancing effect. Asthana’s study used estradiol, a type of estrogen that has been shown to have an effect on the brain. Other studies used a compound that contains low doses of estradiol along with other forms of estrogen that have not been proven to have an effect on the brain, he said. Also, the largest study finding no effect included only women who had hysterectomies. “We don’t know enough yet about how a hysterectomy versus no hysterectomy can affect the brain’s response to estrogen,” he said.
In the current study, the women were given a variety of tests to measure their attention skills, recent verbal memory, recent visual memory and semantic memory, or the ability to name common items from pictures.
The women receiving estrogen improved their performance on an attention test by 20 percent more than the women receiving a placebo. Those receiving estrogen also improved on some of the tests of recent verbal and visual memory by 35 and 30 percent more than those receiving a placebo. On the test of semantic memory, those taking estrogen performed 10 percent better than those taking a placebo.
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Age-related depletion of nitric oxide synthase cofactors may change the antihypertensive effect of estrogen into a prohypertensive effect. (2005) www.sciencedaily.com
From the article:
They were studying estrogen’s effects on blood vessels, focusing on its impact on the smooth muscle cells that allow blood vessels to contract, thereby regulating blood pressure and blood flow. These researchers found that estrogen targets nitric oxide synthase 1, one of three versions of the enzyme that makes the powerful vasodilator, nitric oxide.
“What we were finding is that estrogen seems to be what you might call a natural nitroglycerin; nitroglycerin also works by making nitric oxide,” Dr. White says.
Then they tried to block estrogen’s activity by blocking nitric oxide. “What surprised the heck out of me was after we blocked nitric oxide production and added estrogen, we got a contraction,” says Dr. White. “Estrogen now had turned into a constrictor agent, an agent that would increase blood pressure.”
They looked further and found that normal aging decreases levels of the cofactors L-arginine and tetrahydrobiopterin – both critical to nitric oxide synthase’s production of nitric oxide.
[…]
“Under normal conditions, such as a pre-menopausal woman, this enzyme, nitric oxide synthase, makes nitric oxide,” says Dr. White. “But if you block the production of nitric oxide, this nitric oxide synthase now has a secondary product that normally isn’t made in an appreciable form. Now it makes a compound called superoxide. It’s an oxidant, and oxidation is bad in general. It causes a lot of cellular damage. But what we also have found is that now, instead of causing relaxation, it causes constriction. So you completely flip-flop the response here.
“One of the things this means is that menopause is a good thing, a sort of revolutionary endocrinology idea,” says Dr. White.
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Women whose breast cancer came back after treatment had almost twice as much estradiol in their blood than did women who remained cancer-free. (2008) www.sciencedaily.com
From the article:
In the current nested case-control study, 153 WHEL [Healthy Eating and Living Study] participants whose cancer had recurred were matched with 153 participants who remained cancer-free. These pairs were alike in terms of tumor type, body size, age, ethnicity, use of chemotherapy and other variables. Two-thirds of the participants were using tamoxifen, Rock said.
When they enrolled, researchers tested the women’s blood for concentrations of the steroid hormones estradiol (the primary human estrogen) and testosterone. They analyzed different forms of estradiol and testosterone in the blood, such as how much was bound to transport proteins (such as to the sex hormone binding globulin, or SHBG) and how much was “free” circulating and able to enter a cell.
Researchers found that higher estradiol concentrations, in all forms, significantly predicted cancer recurrence. Overall, women whose cancer came back had an average total estradiol concentration that was more than double the average for women who remained cancer-free. Increased levels of testosterone or SHBG levels were not associated with recurrence, contradicting the findings of several previous studies.
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Perimenopausal estradiol fluctuations may increase women's sensitivity to social rejection and vulnerability to developing depressive symptoms. (2015) www.sciencedaily.com
From the article:
In addition, the menopausal transition and early postmenopausal period are times of particularly increased vulnerability to depression for women, with rates of MDD [major depressive disorder] and clinical elevations in depressive symptoms doubling or even tripling compared to premenopausal and late postmenopausal rates. A substantial proportion of women–between 26% and 33%–will develop clinically significant depressive symptoms within the context of perimenopausal hormonal flux.
The common physiological change occurring during the menopausal transition is extreme variability in estradiol concentrations, thus prompting the 12-month placebo-controlled randomized trial evaluating the mood and cardiovascular benefits of transdermal estradiol in perimenopausal women. The findings from the placebo group found that, in general, estradiol variability led to the development of depressive symptoms, as well as greater anger/irritability and feelings of rejection. More specifically, the findings suggest that perimenopausal estradiol fluctuation may increase women’s sensitivity to social rejection, and when this sensitivity is combined with psycho-social stressors such as divorce or bereavement, women are particularly vulnerable to developing clinically significant depressive symptoms. Of note, however, is that the effect of estradiol variability on mood is not the same in all women and, if a severe life stress did not occur, estradiol variability did not lead to depression. Very severe life stresses were defined and included divorce or separation, serious illness of a close relative or friend, significant current financial issues, physical or sexual abuse or assault, significant arrest of self or loved one.
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Estrogen metabolites may promote lung cancer - including enhancing the effects of tobacco smoke on the disease, mouse study suggests. (2012) www.sciencedaily.com
From the article:
To investigate, Peng, Clapper and their colleagues examined the lungs of healthy mice and found that they contained high levels of estrogen metabolites, known as 4‑hydroxy- estrogens (4-OHEs), which are carcinogenic. Specifically, these 4-OHEs help activate processes that promote cell growth, and generate free radicals that damage cells.
When the researchers exposed the mice to tobacco smoke for 8 weeks, they found that the levels of 4-OHEs increased. “We believe that these metabolites of estrogen can damage cells and contribute to lung cancer,” says Clapper.
Female mice had twice as much 4-OHE in their lungs compared to male mice after controlling for the level of total estrogen present. Whether this is the same in humans remains to be determined. “While lung cancer is not more common in women, the number of nonsmokers who develop lung cancer is greater for men than for women,” explains Clapper.
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Tumor cell-independent estrogen signaling may drive disease progression by mobilizing immune cells associated with tumor treatment resistance. (2016) www.sciencedaily.com
From the article:
Conejo-Garcia and colleagues found that estrogen signaling is closely linked to both the accumulation and activity of myeloid-derived suppressor cells (MDSCs), a set of immune cells associated with tumors treatment resistance. Estrogen enables immunosuppression in a two-pronged approach involving MDSCs. First, the estrogen drives the mobilization of MSDCs. Then, at the same time, it makes a subset of the MDSCs more immunosuppressive in vivo. Estrogen supplementation accelerated the growth of multiple models estrogen-insensitive tumors in immunocompetent animals, while ablating estrogen production by resecting the ovaries boosted anti-tumor immunity and delayed malignant progression. Importantly, differences in tumor progression disappeared in immunodeficient mice, demonstrating that estrogen-mediated acceleration of tumor growth depends on dampening protective anti-tumor immunity.
They also demonstrated how ERα is responsible for enhancing the activity of multiple pathways that are already associated with cancer development. This estrogen receptor activated the STAT3 pathway, which has already been linked to cancer cell survival and the expansion of MDSCs in cancer-bearing hosts. It was also able to activate this pathway by enhancing the activity of JAK2 and SRC, two proteins linked to cancer development and immune response.
These cancer pathways are activated in a variety of inflammatory cancers in non-tumor cells, such as breast cancer, ovarian cancer, and melanoma. Since estrogen is present not just pre-menopausal women but men and post-menopausal women as well, the authors propose that investigating anti-estrogen therapeutic strategies could lead to new treatments for a variety of cancers. This strategy could halt the mobilization of MDSCs and tumor initiation.
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High estradiol levels may interfere with latent inhibition, resulting in impaired attention and learning, rat study suggests. (2010) www.sciencedaily.com
From the article:
Human females have high estrogen levels while they are ovulating. These high levels have also been shown to interfere with women’s ability to pay attention.
[…]
Latent inhibition is observed in many species and is believed to be the important part of learning, which enables individuals to interact successfully in their environment. It is a test of new memory formation.
In the Brake protocol, rats received a pre-exposure phase during which they were repeatedly exposed to a tone, with no consequence. Once they became used to this tone and ignored it, the test dynamics changed and another stimulus was linked to the tone. Rats with low levels of estrogen quickly learned that the tone was associated with the new stimulus whereas those with higher levels of estrogen took longer to form this memory.
“We only observed this effect in adult female rats,” says Brake. “This and our other findings indicate that estrogen directly effects the brain, perhaps by interfering with brain signaling molecules. Our study helps clear up the controversy about the effects of estrogen, the next step is to look at how this occurs.”
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Estrogen may exert inhibitory effects on immune cells, leading to reduced vascular inflammation and protection against cardiovascular disease. (2011) www.sciencedaily.com
From the article:
The results could help explain why cardiovascular disease rates tend to be higher in men and why they soar in women after the menopause.
The researchers compared white blood cells from men and pre-menopausal women blood donors. They found that cells from premenopausal women have much higher levels of protein called annexin-A1 on the surface of their white blood cells.
The scientists also found that annexin-A1 and estrogen levels were strongly linked throughout the menstrual cycle.
White blood cells play a vital role in protecting the body from infections. When they are activated they stick to the walls of blood vessels. This process normally helps the cells to tackle infection but if it happens too much, it can lead to blood vessel damage, which in turn can lead to cardiovascular disease. However, when annexin-A1 is on the surface of these white blood cells, it prevents them from sticking to the blood vessel wall.
The new research shows that estrogen can move annexin-A1 from inside the white blood cell, where it is normally stored, to the surface of the cells, thereby preventing the cells from sticking to blood vessel walls and causing vascular damage. This may have important implications in cardiovascular disease.
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Estradiol may induce BDNF/TrkB signaling in non-estrogen-dependent breast cancer to promote brain metastases, mouse study suggests. (2019) www.sciencedaily.com
From the article:
After all, triple negative breast cancers lack estrogen receptors (along with progesterone receptors and HER2, thus the name triple negative), and so these cancers can’t possibly be influenced by estrogen. Right?
[…]
Technically, Cittelly and colleagues including postdoctoral researcher, Maria Contreras-Zarate, PhD, found that estrogen induces astrocytes (brain cells) to produce growth factors called brain-derived neurotrophic factor (BDNF) and Epidermal Growth Factor (EGF), and that these factors turns on two genetic migration/invasion switches in cancer cells, namely TRKB and EGFR.
“This may explain why breast cancers diagnosed in younger women are more likely to metastasize to the brain – pre-menopausal women have more estrogen, and it may be influencing the microenvironment of the brain in ways that aid cancer,” Cittelly says.
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Estrogen increased the quantity and half-life of dopamine released by rat neurons in response to cocaine, making them addicted more quickly. (2017) www.sciencedaily.com
From the article:
The Mount Sinai research team sought to understand why women, once they try cocaine, are much more likely than men to become addicted. While the overall rate of addiction is higher in males, previous research has shown that when females have the opportunity to try cocaine and other drugs, they are more likely than men to continue use and they transition to full addiction significantly faster than their male counterparts. Addiction investigators have also uncovered that women are more likely to use cocaine at an earlier age, take the drug in larger quantities, and have greater difficulty remaining abstinent compared to men. Additionally, women report that when estrogen levels are rising during their menstrual cycles, they experience a greater “high” from cocaine administration.
[…]
The research team found that estrogen affects the quantity of dopamine released by neurons in response to cocaine, as well as how long the dopamine stays in the synapse between brain cells. Both actions increase the pleasurable effects of cocaine, and each was significantly bolstered as estrogen levels increased in the female mice. Both male and female mice linked pleasure/reward to where it occurred in their cages, spending more time on the side of their cage that was previously paired with cocaine. Female mice did so to a greater extent, indicating enhanced reward to cocaine use.
“The mice quickly learned that a particular environment is linked to drugs, and we demonstrated that when these mice, especially females at the height of their estrous cycle, were put into that environment, it stimulated a dopamine reward signal even without cocaine use,” Dr. Calipari says. “It is the same kind of strong, learned response that we know happens in humans.”
Researchers surmise that the evolutionary mechanism underlying the link between estrogen and the reward pathway is pleasure from seeking a mate and having sex, actions which promote the survival of the species. Another evolutionary hypothesis is that heightened estrogen could promote food seeking, via effects on dopamine signaling, to ensure females are healthy enough to carry offspring.
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Estrogen protected rats against heart attack-related depression by preventing the production of inflammation-causing chemicals in the brain. (2018) www.sciencedaily.com
From the article:
Adult female rats without ovaries – mimicking menopause – were compared to adult males and adult females with ovaries. Half of the “menopausal” rats received estrogen supplements while the other half did not. Sex-matched rats without heart failure served as controls. The animals were given several standardized tests to assess depression-like behavior, learning, memory and the ability to experience pleasure. The researchers also took blood samples to measure inflammation levels in the brain (neuroinflammation).
The male rats, but not the female rats, with heart failure showed signs of depression and brain inflammation compared to their controls. In contrast, the menopausal females displayed higher rates of depression-like behavior than all of the males studied. However, the group receiving estrogen showed no depression – their levels were on par with the control females with ovaries – and no increase in inflammation in brain areas involved in mood and pleasure.
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Estrogen may increase susceptibility to inflammatory disease by negatively affecting wound healing and protective lipid mediator circuits. (2012) www.sciencedaily.com
From the article:
To make this discovery, Gronert and colleagues administered a mild abrasion injury to the front of the eye of genetically similar male and female mice, and analyzed wound healing by image analysis. To test the role of estrogen, they gave male mice estrogen eye drops and/or drugs that activate specific estrogen receptors. Gene expression of essential enzymes was quantified for the formation of protective lipid signals, specific receptors that mediate their bioactivity, as well as estrogen receptors in mouse corneas and human/mouse epithelial cell cultures. The formation of protective lipid signals was analyzed by a mass-spectrometry based lipidomic method. They found that estrogen negatively affects a highly evolved protective lipid circuit, called “15-lipoxygenase-Lipoxin A4” that has recently emerged as an important protective pathway in many diseases. This pathway balances the activity of pro-inflammatory signals to promote wound healing and to keep inflammation within safe ranges.
“This study goes a long way to explaining gender differences in inflammation and its resolution,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. “It’s long been known that women suffer more than men from chronic inflammatory diseases such as lupus or rheumatoid arthritis; this study suggests that estrogen itself is responsible for that difference and pinpoints the molecular pathways that estrogen affects. Molecules that promote the resolution of inflammation show promise as new treatments for autoimmune disease.”
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Estradiol administered to the amygdala of a menopause rat model prevented weight and abdominal fat gain and improved glucose tolerance. (2017) www.sciencedaily.com
From the article:
“We know as women age and enter into menopause, they tend to gain body weight and body fat, particularly in the abdominal or ‘belly’ area. Excess abdominal fat greatly increases risk for cardio-metabolic diseases,” says Solomon. “While there are likely many factors that are associated with these risks in menopausal women, estrogen loss is associated with body weight and fat gain during menopause. In fact, estrogen treatment can offset this weight gain in many women.”
The medial amygdala (MeA) is a region of the brain that helps regulate body weight and contains an abundance of estrogen receptors (molecules that respond to estrogen). The researchers used an experimental model in rats, which involves removing the ovaries to mimic the hormonal changes of menopause. They targeted estrogen replacement directly in the MeA and found that it prevented weight and abdominal fat gain and improved glucose tolerance, compared to rats in a placebo group. This suggests that the MeA is important in the metabolic health of menopausal females and may be a useful target for treatment.
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Estrogen therapy initiated around the onset of menopause may protect the hippocampus from shrinking, thereby reducing the risk of Alzheimer's. (2016) www.sciencedaily.com
From the article:
A sample of 80 women who had used estrogen supplements through menopause was compared with 80 women who had never used estrogen supplements. All had participated in the Nord-Trøndelag Health Study (HUNT), a general population-based study in mid-Norway.
[…]
MRIs of the brains of the women in the study showed that those who had taken estrogen supplements throughout menopause had a larger hippocampus. The hippocampus is one of the most important structures for memory and sense of place, and is one of the structures that is affected early in the progression of Alzheimer’s disease.
“We also examined the shape of the hippocampus and found that areas where hormone therapy had the greatest effect are the same areas that are affected by Alzheimer’s disease in its early stages,” says Pintzka.
Other studies have shown that women who start estrogen supplements several years after menopause do not benefit from the same positive effect on the hippocampus.
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Comparing the brains of children with and without autism spectrum disorder, researchers found a 35% decrease in estrogen receptor expression. (2014) www.sciencedaily.com
Estrogen may protect the brain against autism.
Children with autism have fewer estrogen receptors in their brains than children without the disorder, a 2014 study found. The children had low brain levels of proteins involved in estrogen signaling, as well.
Researchers analyzed brain tissue from healthy children and children with autism who had died from non-natural causes. Specifically, they quantified the expression of the estrogen receptor-beta and related proteins in tissue from the prefrontal cortex, an area of the brain involved in social behavior and cognition.
They found that children with autism had 35 percent lower estrogen receptor-beta expression in their brains compared to healthy children. Children with autism also had 38 percent less aromatase, a protein that converts testosterone to estrogen. Levels of other proteins involved in estrogen metabolism were also low.
Estrogen receptor-beta plays important roles in the human brain, where it participates in aspects of movement, behavior, and learning. Evidence suggests estrogen is neuroprotective, and low levels of estrogen contribute to cognitive dysfunction.
Autism is a developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. It typically manifests in early childhood and is more common among boys than girls.
These findings demonstrate that low brain levels of the estrogen receptor-beta and its related proteins are associated with a greater risk of autism, likely due to impaired neuroprotection from estrogen. In clinical trials, sulforaphane, a compound derived from broccoli and broccoli sprouts, reduces the characteristic behaviors associated with autism. Learn more in this clip featuring sulforaphane expert Dr. Jed Fahey.
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Reproductive events related to shorter cumulative endogenous estrogen exposure in women may be associated with higher dementia risk. (2022) www.sciencedaily.com
From the article:
[…] used data from the UK Biobank to examine the risk of all cause dementia and reproductive factors in 273,240 women as well as the number of children in those women and in 228,965 men.
After controlling for age, socioeconomic status, smoking, body mass index (BMI), and other elements, certain events related to shorter cumulative exposure to internally produced estrogen – such as older than average age at first period, younger than average age at menopause, and having a hysterectomy – were associated with higher dementia risk.
Pregnancy, even aborted pregnancy, longer reproductive span, older age at menopause, and use of contraceptive pills were associated with a lower risk of all-cause dementia.
For both men and women, compared with having two children, having no children or four or more were apparently associated with greater risk of dementia.
The study has limitations including the retrospective reporting on reproductive factors that can be subject to bias, and the fact that UK Biobank is a relatively healthy cohort of affluent people of white British ancestry so may not be representative of a broader population.
Gong adds, “Reproductive events related to shorter exposure to endogenous estrogen in women were associated with higher dementia risk, and these findings highlight the vulnerability in dementia risk pertaining to women. However, the similar association between the number of children and dementia risk observed for women and men indicates that the risk variation in women may be more related to social and behavioural factors in parenthood, rather than biological factors involved in childbearing.”
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Estrogen therapy reduced drive for thinness, body dissatisfaction and uncontrolled eating in female athletes with irregular periods. (2018) www.sciencedaily.com
From the article:
Misra compared 109 female athletes with exercise-induced menstrual irregularities with 50 female athletes with normal menstrual cycles and 39 female non-athletes. All of the study subjects were 14-25 years old and were in a normal weight range. The young women’s eating behavior and mental health was evaluated with self-report assessments and questionnaires.
Athletes with irregular periods reported a higher drive for thinness and more mental control over their food intake compared with athletes with regular periods and non-athletes. They also had higher mean body dissatisfaction scores than athletes with regular periods.
Athletes who had irregular menstrual periods were randomly assigned to receive either estrogen replacement through a patch, at a dose that resulted in estrogen levels seen with normal menstrual cycles; a commonly used combined oral contraceptive pill containing estrogen; or no estrogen for 12 months. Athletes randomized to estrogen replacement as a patch also received cyclic progesterone.
Over one year, the groups that received estrogen showed reductions in drive for thinness, body dissatisfaction and uncontrolled eating, compared with those who didn’t receive estrogen. The patch was the most effective, leading to significant decreases in body dissatisfaction and uncontrolled eating.
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Estradiol enhances anti-viral responses in the genital tract of mice infected with herpes simplex virus type 2. (2016) www.sciencedaily.com
From the article:
“If this pathway can be verified in women, then we have laid the foundation to address a number of important public health issues, particularly whether some hormonal contraceptives may be better than others for women who are at higher risk of acquiring sexually transmitted infections, such as in Sub-Saharan Africa, where both HIV-1 and HSV-2 infection rates are high.”
As part of the study, researchers implanted estradiol-releasing pellets into female mice whose ovaries had been removed. The mice then received two rounds of an HSV-2 vaccine, followed by a high dose of the virus.
The researchers saw that the majority of the mice survived and showed less severe disease symptoms, compared to a control group that was not immunized. Further analysis of the molecular pathways underpinning this defensive mechanism revealed that estradiol primes dendritic cells in the vaginal tract to initiate anti-viral T cell immunity.
More specifically, the researchers reported an increase in anti-viral activity unique to the vaginal tract and not found in any other mucosal lining of the body.
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Estrogen treatment and overexpression of the estrogen receptor may cause malignant neuroblastoma cells to mature into neuron-like cells. (2018) www.sciencedaily.com
From the article:
In a previous study, her group discovered that activation of MYCN [gene that drives tumour cell growth and spread and inhibits the maturation of the cells] results in the formation of specific microRNAs, which are relatively small RNA molecules that regulate proteins. Some of these microRNAs disable the estrogen receptor ERalpha. The present study shows that the inhibition of these microRNA molecules or estrogen therapy in combination with an overexpression of the estrogen receptor can cause aggressive neuroblastoma cells with MYCN activation to mature into neuron-like cells which behave more like normal cells.
The researchers studied tumour tissue from patients, cultivated human tumour cells and tumours in mouse models for neuroblastoma. In the mice, the neuron-like cells did not grow as quickly as the original cancer cells, and analyses of the tumour tissue from patients show that those with a high level of the estrogen receptor have a better survival rate that those with a low.
“Our data suggests that estrogen could be a therapeutic method for patients who express high levels of the estrogen receptor,” continues Professor Arsenian-Henriksson. “Another possible therapy could involve deregulating MYCN or upregulating the estrogen receptor and then treating with estrogen. We have previously shown that the deregulation of MYCN leads to a high expression of the estrogen receptor.”
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Osteoporosis therapy consisting of estrogen, vitamin D and calcium reduced prevalence of severe periodontitis in postmenopausal women by 44%. (2017) www.sciencedaily.com
From the article:
In the Menopause article “Association between osteoporosis treatment and severe periodontitis in postmenopausal women,” 492 postmenopausal Brazilian women aged 50 to 87 years, 113 in osteoporosis treatment and 379 not treated, were evaluated to determine whether osteoporosis treatment could help increase the bone mineral density in their jaws and, subsequently, improve overall oral health.
The study found that the rate of occurrence of severe periodontitis was 44% lower in the postmenopausal osteoporosis-treatment group than in the untreated group. Treatment consisted of systemic estrogen alone or estrogen plus progestin, as well as calcium and vitamin D supplements, for a minimum of six months.
“Osteoporosis can occur throughout the body, including the jaw, and lead to an increased risk of periodontal disease,” says Dr. JoAnn Pinkerton, NAMS executive director.
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Unlike transdermal estrogen therapy, oral use may increase the risk of blood clots almost threefold. (2016) www.sciencedaily.com
From the article:
This large population study of more than 800 Swedish women who had VTEs and nearly 900 age-matched controls who took no hormones is helping answer those questions.
In this study, risk of having VTE [venous thromboembolism] was almost twofold higher (OR 1.72) in the women who took hormones than in those who took no hormones, which is similar to other studies, including the WHI. What’s more, women who took combined estrogen-progestogen therapy had nearly three times the VTE risk of those who took no hormones. Women who took estrogen only (because they had had hysterectomies and didn’t need a progestogen) had a much lower overall increase in their odds of VTE–a little less than one and half times higher (OR 1.31) compared with those who took no hormones. Women using combined estrogen-progestogen had a twofold higher risk of VTE than those taking estrogen only.
However, this study had good news about the way estrogen is delivered. There was no increased risk of VTE in this study for women who used transdermal estrogen (such as patches), either alone or in combination with a progestogen. And women who used vaginal estrogen alone to ease vaginal dryness and other symptoms of genitourinary syndrome of menopause (GSM) also had no increased risk of VTE. Many menopause experts don’t expect vaginal estrogen to raise the risk because absorption into the bloodstream is small and results in levels similar to those in postmenopausal women who use no hormones. But studies on this question have been rare, noted the authors, so this finding is a big help for decision making.
Whether the type of progestogen makes a difference in risk has also been an important question for women and clinicians, and there haven’t been many studies on this. Some imply that the VTE risk is higher with medroxyprogesterone acetate (the progestogen used in the WHI) than with norgestrel. But this study didn’t show any statistically significant difference in risk between the two synthetic progestins. What it did show was that having a uterus and taking both oral estrogen and a synthetic progestin increased the risk of VTE the most, particularly compared with estrogen only.
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Long-term postmenopausal estrogen therapy may increase kidney damage risk and adversely affect women with abnormal kidney function - rat study. (2016) www.sciencedaily.com
From the article:
The harmful effect of high blood pressure on the blood vessels is one cause of kidney damage. Estrogen seems to protect against high blood pressure – fewer premenopausal women have high blood pressure than men of the same age – but after menopause, these benefits appear to diminish. Researchers from Tulane University in New Orleans studied a breed of rats that mimic the gender-specific blood pressure differences observed in humans to see if long-term hormone treatment negatively affects the kidneys.
The research team studied three groups of middle-aged rats without ovaries, which simulates the low estrogen environment of menopause. One group (“short-term”) was given a short course of estrogen. A second group (“long-term”) received a longer regimen of estrogen. The estrogen groups were compared to a control group that did not receive hormones.
Researchers found that after the hormone treatments, the long-term group had more damage to the tiny tubes that collect and carry urine than the short-term and control groups. The rate at which the kidneys filtered blood decreased, and creatinine levels and protein in the urine (markers of impaired kidney function) increased in the rats receiving long-term estrogen. The long-term group showed more kidney damage in each marker than the short-term or control groups.
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Higher levels of the "good" estrogen metabolite were associated with a 24-27% reduced risk of all-cause mortality in breast cancer survivors. (2019) www.sciencedaily.com
From the article:
“A lot of research has been done to link these two metabolites with the probability of developing breast cancer,” said the study’s first author Tengteng Wang, a doctoral candidate in the UNC Gillings School of Global Public Health. “So far, we believe we are the first to look at the association of metabolites in relation to mortality after 18 years of breast cancer diagnosis.”
Estrogen is a hormone in the body that drives development of female sex characteristics. Free estrogen in the body is broken down into several byproducts, one of which is 2-hydroxyestrone, or 2-OHE, which is known is a “good” type of byproduct. Researchers report that it is known to interfere with the cancer-linked effects of estrogen. Another metabolite, which is called 16-alpha-hydroxyestrone, is known as a “bad” metabolites because of its pro-cancer effects that lead to abnormal growth and DNA damage.
[…]
In their study, researchers examined the balance of these two metabolites in relation to mortality. Specifically, they found that if the level of 2-OHE was more than, or equal to, 1.8 times the level of 16-alpha-OHE in urine, there was an associated 26 percent reduction in any cause of death in women with breast cancer. They also saw that there was a lower risk of breast cancer death, or cardiovascular death, for women who had higher levels of the “good” metabolite.
They studied these associations in group of 687 women who were diagnosed with breast cancer between 1996 and 1997, and who participated in the Long Island Breast Study Project.
[…]
Researchers say they have additional questions remaining after the study, such as whether the subtype of breast cancer a woman has is important for the pattern they saw, and whether treatments that women may or may not have received could be playing a role as well.
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Transdermal estrogen therapy modestly improved sexual function in early postmenopausal women. (2017) www.sciencedaily.com
From the article:
In the new article, Hugh S. Taylor, M.D., of the Yale School of Medicine, New Haven, Conn., and his coauthors report on an ancillary study of a clinical trial that examined changes in sexual function in recently postmenopausal women. The ancillary study included 670 women given oral conjugated equine estrogens (o-CEE), transdermal 17β-estradiol (t-E2) or placebo.
The women ranged in age from 42 to 58 and were within three years of their last menstrual period.
[…]
– The transdermal treatment was associated with moderate improvement in the overall sexual function score across all time points compared with placebo; there was not a significant difference in overall sexual function score with oral estrogen treatment compared with placebo.
– There was no difference in overall sexual function score between the oral and transdermal estrogen therapy on average across four years.
– In specific areas of sexual function, the transdermal treatment was associated with an increase in average lubrication and decreased pain compared with placebo.
– The proportion of women with low sexual function was lower after transdermal treatment compared with placebo; there was no significant reduction in the odds of low sexual function with oral estrogen therapy.
The study has limitations including the restricted generalizability of its findings because the population of the clinical trial was predominantly white women with a higher educational background than the general population.
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Low-dose estrogen therapy reduced the prevalence of hot flashes from 44% to 4.2% and night sweats from 35% to 4.7% in postmenopausal women. (2016) www.sciencedaily.com
From the article:
KEEPS was a multicenter clinical trial designed to compare effects of low-dose oral conjugated estrogens (CEE) with those of transdermal estradiol versus placebo on cardiovascular endpoints in recently postmenopausal women. Seven hundred twenty-seven women aged 42 to 58 years and within 3 years of their final menstrual period were randomized to receive oral conjugated estrogens (CEE) 0.45 mg (n = 230) or transdermal estradiol 50 μg (n = 225), both with micronized progesterone 200 mg for 12 days each month, or placebo (n = 275).
All participants completed a menopause symptom checklist before randomization and again at 6, 12, 24, 36, and 48 months. Menopause symptoms were self-assessed and included only current symptoms of hot flashes, night sweats, insomnia, and irritability. Because of study dropout from screening to 48 months, 173, 170, and 211 women randomized to CEE, transdermal estradiol, and placebo, respectively, completed the end-of-study assessments.
At baseline screening, moderate to severe hot flashes were reported by 44% of participants. By 6 months, moderate to severe hot flashes had decreased to 28.3% for those women randomized to placebo, 7.4% for those randomized to transdermal estradiol, and 4.2% for those randomized to CEE [oral conjugated estrogens]. Moderate to severe night sweats reported by 35% of participants at baseline decreased to 19% for placebo, 5.3% for transdermal estradiol, and 4.7% for CEE at 6 months. This initial magnitude of symptom reduction was maintained throughout the entire study in all treatment groups.
Insomnia and irritability decreased from baseline to 6 months after randomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus placebo, with CEE being more effective than placebo at 36 and 48 months and transdermal estradiol being more effective than placebo at 48 months. Neither hormone treatment significantly affected irritability compared with placebo.
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Activating a specific estrogen receptor may stop pancreatic cancer cells from growing and make the tumors more visible to the immune system. (2020) www.sciencedaily.com
From the article:
For most cancer types, including pancreas, women generally have better outcomes than men. Although the reasons for this are only now emerging, researchers have known for decades that there is a link between the body’s sex hormones and some types of cancer, especially those arising in reproductive tissues such as breast and prostate. However, the idea that cancers in non-reproductive tissues might also be influenced by sex steroid hormones has only recently been considered.
[…]
Using new PCRC mouse pancreatic cancer models, the multidisciplinary team was able to show GPER’s [G protein-coupled estrogen receptor] impact on pancreatic cancer growth. In some models, GPER [G protein-coupled estrogen receptor] activation inhibited growth and made tumors more sensitive to anti-PD-1 immunotherapy, pointing to the translational potential of improving the efficacy of existing treatments in a cancer type where PD-1 inhibitors have not historically been very effective.
The use of GPER activators is a novel idea in cancer therapy, and has a key difference from most anti-cancer agents. Nearly all current cancer drugs act to block the activity of cellular proteins that are needed by not only the cancer cells, but also by normal cells. As a result, most cancer drugs are associated with major toxicity. In contrast, the estrogenic analog used in the Penn study activates GPER. This approach mirrors something that naturally occurs in the body, as GPER is already present and normally activated by estrogen, especially in females during pregnancy.
“Likely because this is something the human body is already accustomed to, evidence from preclinical animal studies suggested that side effects to this approach would likely be minimal when this moves into the clinic,”
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The brain's reward center may be much more sensitive to the addictive effects of alcohol during estrogen-rich periods of the menstrual cycle. (2017) www.sciencedaily.com
From the article:
“When estrogen levels are higher, alcohol is much more rewarding,” said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. “Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages.”
Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.
[…]
“In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop,” Lasek said.
VTAs [ventral tegmental area - “reward center”] were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.
Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The estrogen receptor blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from mice in estrus were unaffected by the estrogen receptor blocker.
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Study in mice suggests that overexpression of estrogen receptor 1 gene can impact post-menopausal breast cancer risk and prevention strategies. (2022) www.sciencedaily.com
From the article:
In a study using a first-of-its kind mouse model of aging that mimics breast cancer development in estrogen receptor-positive post-menopausal women, investigators at Georgetown Lombardi Comprehensive Cancer Center and colleagues have determined that over-expression, or switching on of the Esr1 gene, could lead to elevated risk of developing estrogen receptor-positive breast cancer in older women.
In a second study from the same research lab, investigators found that in the specially bred mice given anti-hormonal drugs (e.g., tamoxifen and letrozole) similar to those currently used by women to lower their breast cancer risk, the elevated risk of developing breast cancer due to over-expression of Esr1 could be lowered or reversed.
[…]
“If validated in human studies, detection of over-expression of Esr1-related genes could be a new signature to add to current prognostic tools that would help post-menopausal women at risk for estrogen receptor-positive breast cancer decide what their best risk reduction strategy might be.”
[…]
The investigators were guided in their study by the use of the PAM50 (Prediction Analysis of Microarray 50) prognostic tool. The tool reads a sample of the tumor and determines expression levels for a group of 50 genes. The scientists found that many genes related to proliferation of breast cancer cells in the PAM50 tool were significantly expressed only in Esr1 mice and this correlated with development of the same type of estrogen receptor-positive breast cancers that develop in humans, thereby giving them new evidence of which other genes might be implicated in inducing breast cancer in post-menopausal women. In current clinical practice, the results of the PAM50 test have helped predict the chance of metastasis for some ER-positive, HER2-negative breast cancers.
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The omega-3 fatty acid DHA increased estradiol production in the brains of mice by more than twofold, thereby suppressing induced seizures. (2017) www.sciencedaily.com
From the article:
One group was fed a diet consisting of soybean oil, another on cottonseed oil, and a third on cottonseed oil in addition to DHA supplements.
These two oils used were chosen due to the differing yields of DHA obtained from them, i.e. the body produces more DHA from soybean oil than cottonseed oil. The third group were also fed on cottonseed oil, but also crucially along with DHA supplements.
After 28 days on these diets, the three groups were exposed to seizure inducing drugs. The group fed on soybean oil took longer to exhibit seizures, and when they did occur they were of a shorter duration than those fed on cottonseed oil. However, the mice fed on cottonseed oil with DHA supplementation, took far longer for seizures to take hold – proving that dietary sourced DHA was a key contributing factor.
When the researchers examined the brains of these mice they found that the soybean oil fed ones had over twice the concentration of estrogen present as those fed solely on cottonseed oil. The mice fed on cottonseed with DHA supplementation had even higher levels of the hormone, suggesting that estrogen production affects seizures, and that this is directly connected to DHA’s presence.
In order to prove this link between estrogen concentration in the brain and omega-3 fatty acid intake/DHA-synthesis, a second experiment was carried out.
This time, one group of mice were again fed on cottonseed oil, and another group on cottonseed oil with DHA supplementation. In addition, a third group was fed on cottonseed oil with DHA supplements – and also Letrozole – a drug which prevents estrogen synthesis.
When seizures were induced this time round, the group exposed to Letrozole were found to have seizures much earlier than those fed on cottonseed fortified with DHA, thus confirming estrogens importance in preventing seizures.
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Monkey study suggests that estrogen produced in the brain may play a role in ovulation and undiagnosed infertility problems. (2017) www.sciencedaily.com
From the article:
They implanted capsules under the monkeys' [who’d had their ovaries removed] skin that released estradiol, fooling their brains into thinking there were ovaries at work preparing for ovulation. At the same time, the scientists kept the animals from making any of their own estrogens by inhibiting the work of an enzyme, aromatase, necessary for estrogen production.
Without the help of estradiol produced by the monkeys, the rising release of luteinizing hormone began, but fell short of the full surge required to spark ovulation by about 70 percent compared to animals whose estrogen production wasn’t suppressed.
To zero in on where the estrogen was doing its work, the researchers repeated the process, but blocked estradiol production specifically in the hypothalamus in the monkeys. They watched for the emergence of hypothalamic hormones – called gonadotropin-releasing hormone and kisspeptin – that indicated the key neurons were ramping up to cue the luteinizing hormone surge.
In this case, the releases of all three ovulation-signaling hormones were reduced, indicating that the brain was where the estradiol effects were happening.
“The ovarian estrogen starts the surge, but the brain estrogen allows the surge to continue,” says Kenealy. “When we block the production of brain estrogen, we still start the surge, but basically we cut the top off the mountain and the surge is drastically reduced.”
“This shows the brain’s estrogen is a huge helper, necessary for the release of an egg that makes pregnancy possible”
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Estrogen increases blood-forming stem-cell self-renewal in females and during pregnancy, mouse study suggests. (2014) www.sciencedaily.com
From the article:
[The study authors] discovered that blood-forming stem cells divide more frequently in females than in males due to higher estrogen levels. The research, conducted using mice, demonstrated that the activity of blood-forming stem cells was regulated by systemic hormonal signals in addition to being regulated by local changes within the blood-forming system.
“This discovery explains how red blood cell production is augmented during pregnancy,” said Dr. Morrison. “In female mice, estrogen increases the proliferation of blood-forming stem cells in preparation for pregnancy. Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production.”
The study involved treating male and female mice over a period of several days with amounts of estrogen needed to achieve a level consistent with pregnancy. When an estrogen receptor that is present within blood-forming stem cells was deleted from those cells, they were no longer able to respond to estrogen, nor were they able to increase red blood cell production The results demonstrate that estrogen acts directly on the stem cells to increase their proliferation and the number of red blood cells they generate.
“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell-formation,” said Dr. Morrison. “Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”
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Low estrogen levels increase a woman's risk for PTSD. www.nature.com
Estrogen may protect women against post-traumatic stress disorder (PTSD), according to findings from a 2017 study. Women are more likely to experience PTSD following a traumatic event if their estrogen levels are low.
The study involved 239 women who had been diagnosed with PTSD. Because methylation turns on or off the activity of genes, researchers analyzed methylation patterns in the women’s DNA to see how estrogen influenced gene activity.
They found that estrogen levels were associated with DNA methylation across the women’s genomes. In particular, estrogen influenced the activity of a gene called HDAC4, which plays important roles in memory and fear processing. Women who carried certain variants of HDAC4 exhibited an impaired ability to deal with and recover from a traumatic event. They also had stronger connections in regions of their brains involved in fear learning.
PTSD is a neuropsychiatric disorder that may occur in people who have experienced or witnessed a traumatic event. As many as 3 million people living in the United States will be diagnosed with PTSD each year.
These findings demonstrate that estrogen influences a woman’s risk of developing PTSD and suggest that estrogen may be useful as a therapeutic measure following exposure to a traumatic event. Some evidence suggests that psychedelic drugs may be useful in treating PTSD. Learn more in this clip featuring Dr. Roland Griffiths.
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Long-term estrogen supplementation may affect gut microbiome composition and thus estrogen metabolism. (2018) www.sciencedaily.com
From the article:
“Our findings indicate that clinicians might be able to manipulate the gut biome through probiotics to change the half-life and properties of estrogens so that long-term users obtain the therapeutic benefits of estrogen-replacement therapy without increasing their risks of reproductive cancers,” said Madak-Erdogan, also the director of the Women’s Health, Hormones and Nutrition Lab at the U. of I.
[…]
“We observed that both levels of fecal _GUS [B-glucuronidase] activity and glucuronic acid – a byproduct of estrogen metabolism – decreased after the mice were treated with conjugated estrogens and bazedoxifene_ [selective estrogen receptor modulator (SERM)],” Madak-Erdogan said. “This supported our hypothesis that estrogen supplementation affects the gut microbiome composition and estrogen metabolism.
“While the overall diversity of microbiota was not changed significantly, we found that the activities of several bacteria taxa were altered by the estrogen therapy,” Madak-Erdogan said. “The levels of several bacteria associated with GUS [B-glucuronidase] activity in the gut decreased, including levels of akkermansia,” a family of bacteria believed to have anti-inflammatory properties in humans.
[…]
However, mice with higher levels of akkermansia in their fecal biome gained more weight, had larger livers and more estrogen metabolites in their systems, the researchers found.
In examining the abundance of common bacterial families in the fecal microbiota, the researchers found higher levels of several microbes, including lactobacillus and streptococcus. Lactobacillus was shown to be associated with GUS activity in previous studies by other researchers while GUS was identified in a subspecies of streptococcus.
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Estrogen may fuel need for power and control in women. (2008) www.sciencedaily.com
From the article:
“However, estrogen is very behaviorally potent and is actually a close hormonal relative to testosterone. In female mammals, estrogen has been tied to dominance, but there has been scant research examining the behavioral roles of estrogen in women.”
[…]
Schultheiss and Stanton measured women’s power needs and then assessed salivary estrogen levels both before and after they entered a one-on-one dominance contest.
The researchers found that even before women got involved in the contest, higher power motivation was associated with higher levels of estrogen.
Winners of the contest showed even further increases in estrogen after the contest, but only if they had a strong need for power. Notably, this increase could still be detected one day after the contest was over.
In contrast, power-motivated losers showed a post-contest decrease in estrogen. These effects were not observed among women who did not possess a strong need for power.
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Estrogen's effects on fat-mobilization promotes a pear shape in pre-menopausal women, but may promote abdominal accumulation after menopause. www.sciencedaily.com
From the article:
Gavin and her colleagues recruited 17 overweight-to-obese premenopausal women, all between the ages of 18 and 44 years old. […] Participants performed this [submaximal] exercise both by itself and while the [fat-mobilizing] drugs were being infused. To test the effects of estrogen, the researchers also performed each of these conditions while estrogen was also being slowly infused into participants' fat deposits.
Results
The researchers found that estrogen’s effects differed tremendously depending on the fat-mobilizing interventions themselves and where the fat deposit was located. For example, estrogen blunted fat breakdown in the abdomen if it was infused while a particular fat-mobilization drug called isoproterenol was also being infused, but it didn’t have this effect in the buttocks. When a second fat mobilizing drug was given along with the first while participants were at rest, fat breakdown didn’t change any further. However, when both drugs were injected together during exercise or when the volunteers exercised without the drugs, fat breakdown increased in the abdomen, but less so in the buttocks.
Importance of the Findings
These results suggest that estrogen has different effects within fat tissue depending on its location. Together, these effects could help maintain premenopausal women’s “pear” shape even in the face of exercise or other signals the body receives to break down fat. They could also help generate some new ideas on how estrogen in fat may influence why postmenopausal women tend to accumulate more fat in the abdomen.
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Estradiol may act as a regulator of muscle energy metabolism and muscle cell viability: loss of estrogen in menopause may promote sarcopenia www.sciencedaily.com
From the article:
The effects of estrogen on skeletal muscles are not yet well known. The study from the University of Jyväskylä discovered that estrogen acts as an upstream regulator for the energy metabolism and viability of muscle cells.
[…]
“These findings help to understand why menopausal women’s muscles get smaller and their muscle strength diminishes,” Dr. Laakkonen explains. Skeletal muscle is important for whole-body metabolism. Therefore, these results are important when fighting against the elevated risk of metabolic diseases associated to aging.
In total 24 pre- and postmenopausal women participated in this muscle research on middle-aged women.
From the publication:
The major canonical pathways found to be differentially regulated included mitochondrial dysfunction, oxidative phosphorylation, glycolysis, and TCA-cycle, strong indicators for affected energy metabolism. The major biological processes predicted to be affected were related to cell death, apoptosis, and cell survival, as well as contractility of the muscle and glycolysis. Furthermore, E2 [17β-estradiol] was predicted to be an upstream regulator of these processes, which we confirmed by exposing myotubes to E2 in vitro.
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Estrogen-sensitive brain circuit may help women control obesity by stimulating physical activity and thermogenesis, animal study suggests. (2022) www.sciencedaily.com
From the article:
The team reveals in the journal Science Advances an estrogen-activated neurocircuit that stimulates thermogenesis, or body heat production, and physical activity in animal models. The circuit begins in neurons located in a region of the hypothalamus called the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH). These neurons interact with estrogen via estrogen receptor-alpha (ER-alpha) and respond to the hormone by connecting to and communicating with serotonin-producing neurons located in another brain region called dorsal raphe nucleus (DRN).
The circuit not only responds to estrogen, but also to changes in ambient temperature and in the nutritional status of the animal. Interestingly, the circuit seems to be functional in males but, at this point, its physiological relevance is not clear.
[…]
“For example, the circuit can be activated when it’s cold, stimulating thermogenesis and physical activity, which would help the animal stay warm,” Xu said. “The circuit can be inhibited when the animal is hungry, which would shut down thermogenesis and physical activity, saving energy to adapt to the lack of nutrients.”
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Estrogen may protect against fear overexpression during the recall of fear and extinction memories. (2021) www.sciencedaily.com
From the article:
Participants underwent a fear-conditioning paradigm in which two of four photographs of neutral male faces were paired with a loud burst of white noise. Following the conditioning, the subjects underwent fear extinction, in which two photographs – only one of which had been paired with the noise – were again presented, but this time with no noise stimulus. The next day, subjects were shown all four photographs again, including the two that had been presented in the extinction phase and thus ready for extinction recall, and two of them without previous extinction – thus subject to fear recall. During all presentations, the researchers measured skin conductance responses (SCR), a peripheral readout of fear expression, and brain oscillations measured by electroencephalography.
Mr. Bierwirth said: “We found stronger peripheral fear expression (via SCR) during fear recall and extinction recall under low-E2 conditions, that is, in men and in OC women, compared to mid-cycle women with higher E2 [estradiol] levels. Most importantly, we also observed enhanced theta oscillations in the medial prefrontal cortex and especially in the dorsal anterior cingulate cortex (dACC), in men and OC women compared to MC women.”
Importantly, the authors also point out that subjects were examined during their natural E2 status. They were not randomized to experimentally manipulated estrogen levels and so causal inferences about estrogen cannot be drawn.
Fear recall-related dACC theta oscillations were attenuated in women with higher E2 levels, which, importantly, supports previous findings suggesting a protective role for E2 against fear overexpression during the recall of fear and extinction memories. The data demonstrate that peripheral and brain oscillatory correlates of fear memory recall do not differ between the sexes per se but vary with E2 status, even among women.
From the publication:
Rodent studies show that theta oscillations (4–8 Hz) in the prelimbic cortex (homolog of the primate dACC) were augmented during fear recall and reduced to baseline levels during extinction recall.
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Estrogen may protect bone density by inducing osteocyte expression of the protein semaphorin-3A, mouse study suggests. (2019) www.sciencedaily.com
From the article:
Our laboratory recently discovered that bone matrix is maintained by a protein called Sema3A, which is secreted by osteocytes. This led us to suspect that there might be a mechanistic relationship between estrogen and Sema3A."
Sema3A does indeed appear to be linked to estrogen: the researchers found that blood serum levels of the protein decrease in premenopausal women as they get older – and drop even further once women reach menopause. But how, at the biological level, are estrogen and Sema3A related? And what is Sema3A doing in bone tissue?
[…]
“When we genetically removed Sema3A from the osteoblast lineage cells (including osteocytes) of mice, we found that intravenous estrogen no longer prevented bones from deteriorating after an ovariectomy,” lead author Mikihito Hayashi describes. “In addition, we found that Sema3A sets off a chain of signaling events that promote the survival of osteocytes in these mice. This suggests that Sema3A serves as a key mechanistic link between estrogen and bone maintenance.
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Estrogen may contribute to T cell–mediated autoimmune inflammation by promoting T cell activation and proliferation, mouse study suggests. ( 2018) www.sciencedaily.com
From the article:
Estrogen hormone shows its action on cells mostly through (ERα). Researchers from Turku generated mice with ERα protein specifically deleted in T cells.
“The eureka moment of our research is that in a mouse model of human inflammatory bowel disease, transfer of naive T helper cells from ERα [estrogen receptor alpha] deficient mice did not succumb to colitis, unlike transfer from their counterparts,” Docent Zhi Chen tells.
“Furthermore, using cutting-edge technique RNA sequencing approach combined with in vitro and in vivo experiments, we discovered that ERα regulates multiple aspects of T cell function, including T cell activation, proliferation and survival,” Chen adds.
Regulatory T cells are group of T cells that help in preventing autoimmune diseases. The researchers found that ERα influences the function and differentiation of regulatory T cells.
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Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD). (2017) www.sciencedaily.com
From the article:
The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification of DNA that is usually a sign of genes that are turned off.
[…]
“We knew that estrogen affects the activity of many genes throughout the genome,” […] “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”
That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning.
On top of that, experiments with female mice showed that the HDAC4 gene was activated in the amygdala while the mice were undergoing fear learning, but only when estrogen levels in the mice were low.
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Neuron-derived estrogen may regulate synaptic plasticity and memory, mouse study suggests. (2019) www.sciencedaily.com
From the article:
Brann and his colleagues found that mice whose neurons don’t make estrogen have impaired spatial reference memory – like a baseball player not knowing where home plate is and what it means to get there – as well as recognition memory and contextual fear memory – so they have trouble remembering what’s hazardous – they report in the Journal of Neuroscience.
Restoring estrogen levels to the brain area rescues these impaired functions, Brann and his colleagues report.
It was known that aromatase, the enzyme that converts testosterone to estrogen, was made in the brain’s hippocampus and cerebral cortex in a variety of species that includes humans, Brann says, and that they all can have memory deficits when aromatase is blocked. Patients who take an aromatase inhibitor for estrogen-dependent breast cancer also have reported memory problems.
[…]
Knocking out aromatase also decreased expression of CREB, a major transcription factor known to play a key role in learning and memory, the scientists write, as well as neuron-nourishing brain derived neurotrophic factor, or BDNF.
[…]
The scientists say these findings implicate neuron-derived estrogen as a novel neuromodulator, basically a critical messenger one neuron relies on to communicate with others, which is essential to key functions like cognition.
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Estrogen may improve insulin sensitivity and suppress gluconeogenesis via Foxo1, mouse study suggests. (2019) www.sciencedaily.com
From the article:
“Premenopausal women exhibit enhanced insulin sensitivity and reduced incidence of Type 2 diabetes compared with age-equivalent men,” he explained. “But this advantage disappears after menopause with disrupted glucose homeostasis, in part owing to a reduction in circulating estrogen.”
[…]
“We wanted to understand the mechanism by which estrogen regulates gluconeogenesis by means of interaction with hepatic Foxo1,” he explained. “Foxo1 has an important role in the regulation of glucose production through insulin signaling. It is an important component of insulin-signaling cascades regulating cellular growth, differentiation and metabolism.”
He said in both male and ovariectomized female control mice, a subcutaneous estrogen implant improved insulin sensitivity and suppressed gluconeogenesis. However, the estrogen had no effect on the liver-specific Foxo1 knockout mice of both sexes.
“This suggests Foxo1 is required for estrogen to be effective in suppressing gluconeogenesis,” he said.
“We further demonstrated that estrogen suppresses hepatic glucose production through activation of estrogen receptor signaling, which can be independent of insulin receptor substrates Irs1 and Irs2. This reveals an important mechanism for estrogen in the regulation of glucose homeostasis.”
Guo said study results support the hypothesis that improvement of glucose homeostasis by estrogen is regulated by hepatic Foxo1-mediated gluconeogenesis rather than by promoting muscle glucose uptake.
[…]
Guo also noted some foods, such as soybeans, contain a certain amount of phytoestrogens, which can function in a similar way to that of estrogen, regulating bodily glucose metabolism and insulin sensitivity.
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Neuron-derived estrogen may be critical for astrocyte activation and neuroprotection of the ischemic brain, mouse study suggests. (2020) www.sciencedaily.com
From the article:
In the face of low brain oxygen that can occur with stroke or other brain injury, these astrocytes, star-shaped brain cells that help give the brain its shape and regularly provide fuel and other support to neurons, should become “highly reactive,” increasing cell signaling, releasing neuroprotective factors and clearing neurotoxins, scientists report in The Journal of Neuroscience.
[…]
To try to understand how astrocytes take on this enhanced role, they knocked out the enzyme aromatase, which is critical to estrogen production, in neurons in the forebrain, the largest region of the human brain, in their animal model.
They found that one way estrogen made by neurons is protective in ischemia is by suppressing signaling of the fibroblast growth factor, FGF2, which is also made by neurons and known to suppress astrocyte activation, Brann and his colleagues write. Normally neurons use this FGF2 brake to help keep astrocyte response from getting out of control.
[…]
In this scenario, when they used a neutralizing antibody to block FGF2, astrocytes became more active and neuron damage was decreased. “The astrocyte activation came back and we saw the protective growth factors that they make,” Brann says. Giving more estrogen produced similar benefits, including improving cognition after ischemia.
[…]
They also saw less of known neuroprotective growth factors, like brain derived neurotrophic factor and insulin-like growth factor 1, which astrocytes normally release at an increased rate in response to a stressor like ischemia, and more suppressive substances like the brake FGF2 [when the estrogen producing enzyme aromatase was knocked out].
[…]
Activated astrocytes also help clear glutamate, the brain’s most abundant excitatory neurotransmitter that normally helps neurons communicate. But without estrogen from the neurons, the glutamate transporter, GLT-1, which removes about 90% of the glutamate, is significantly decreased and the chemical can accumulate at toxic levels in the brain and become a major cause of neuron destruction. “Glutamate is essential for brain function, but if it’s overproduced, it’s brain toxic,” Brann says.
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Vitamin D and estradiol may synergistically help protect against metabolic syndrome. (2019) www.sciencedaily.com
From the article:
Metabolic syndrome has emerged as a major public health concern, affecting 30% to 60% of postmenopausal women worldwide.
[…]
The cross-sectional study included 616 postmenopausal women aged 49 to 86 years who were not taking estrogen and vitamin D/calcium supplements at the beginning of the trial. It concluded there was a positive correlation between vitamin D and estradiol.
Specifically, higher vitamin D was associated with a favorable lipid profile, blood pressure, and glucose level. Estradiol was negatively associated with cholesterol, triglycerides, and blood pressure. These results suggest a synergistic role of vitamin D and estradiol deficiency in developing metabolic syndrome in postmenopausal women.
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Estrogens may act on distinct hypothalamic neurons to regulate energy homeostasis and reproduction, mouse study suggests. (2011) www.sciencedaily.com
From the article:
“When women approach menopause, they gain weight in fat and their energy expenditure goes down,” says Deborah Clegg of the University of Texas Southwestern Medical Center. Estrogen levels decline and women grow increasingly susceptible to obesity and metabolic syndrome.
Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone’s influence on metabolism, Clegg suspected receptors in the brain.
[…]
The researchers showed female mice lacking ERα [estrogen receptor-α (ERα)] in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERα from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERα receptors in those same neurons also led to various problems in ovulation and fertility.
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Doubling of estrogen and progesterone levels was associated with lower odds of snoring (-19%) and symptoms of sleep apnea (-23%) in women. (2022) www.sciencedaily.com
From the article:
In the new study, the researchers analyzed data from 774 women aged 40 to 67 in the European Community Respiratory Health Survey, conducted in seven countries between 2010 and 2012. Women in the study participated in questionnaires on their respiratory health, women’s health factors, lifestyle and sleep, and gave blood samples for hormone analysis.
551 of the women in the study (71.2%) had been told they snored, and 411 of those women also reported other symptoms of sleep apnea. Among all women, a doubling of serum concentrations of estrone was associated with 19% decreased odds of snoring. A doubling of progesterone levels was associated with 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of three estrogens (17β-estradiol, estrone and estrone 3-sulfate) was associated with 17% to 23% decreased odds of women having been told they breathe irregularly during sleep. A doubling of progesterone concentration, among snorers, was associated with 12% decreased odds of having woken with a choking sensation in the previous year.
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The brain may be capable of rapidly producing and releasing large amounts of estrogen, animal study suggests. (2013) www.sciencedaily.com
From the article:
“Discovering that the hypothalamus can rapidly produce large amounts of estradiol and participate in control of gonadotropin-releasing hormone neurons surprised us,” says Ei Terasawa, professor of pediatrics at the UW School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. “These findings not only shift the concept of how reproductive function and behavior is regulated but have real implications for understanding and treating a number of diseases and disorders.”
For diseases that may be linked to estrogen imbalances, such as Alzheimer’s disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders, the hypothalamus may become a novel area for drug targeting, Terasawa says. “Results such as these can point us in new research directions and find new diagnostic tools and treatments for neuroendocrine diseases.”
[…]
In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges.
In the second experiment, mild electrical stimulation of the hypothalamus caused the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action). Third, the research team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain.
[…]
Leading up to this discovery, Terasawa said, recent evidence had shown that estrogen acting as a neurotransmitter in the brain rapidly induced sexual behavior in quails and rats.
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Estrogenic compounds reduced flu virus replication in nasal cells from women but not men. (2016) www.sciencedaily.com
From the article:
To examine how estrogen affected the flu virus’s ability to replicate, the research team gathered nasal cells – the cell type that the flu virus primarily infects – from male and female donors. The researchers exposed the cell cultures to the virus, estrogen, the environmental estrogen bisphenol A and selective estrogen receptor modulators (SERM), which are compounds that act like estrogen that are used for hormone therapy.
The researchers found that estrogen, SERM compound raloxifene and bisphenol A reduced flu virus replication in nasal cells from women but not men. They also observed that the estrogens initiated their antiviral effects through estrogen receptor beta. Receptors are protein structures that molecules bind with to induce cells to respond.
According to Klein, “Other studies have shown that estrogens have antiviral properties against HIV, Ebola and hepatitis viruses.”
[…]
“But, premenopausal women on certain kinds of birth control or post-menopausal women on hormone replacement may be better protected during seasonal influenza epidemics,” she says.
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For women, greater exposure to estrogen in life may protect brain regions that are vulnerable to Alzheimer’s. (2021) www.sciencedaily.com
From the article:
The analysis covered 99 women aged 46-58 and a comparison group of 29 similarly aged men. It confirmed that the post-menopausal and peri-menopausal (starting menopause) women, compared with the pre-menopausal women and the men, had significantly lower GMV – adjusted for age and head size – in brain areas such as the hippocampus, entorhinal cortex and temporal lobe regions, which are heavily affected by Alzheimer’s.
By contrast, among the women, having more estrogen exposure as implied by various factors was associated with greater GMV [gray matter volume] in certain brain areas. Longer reproductive span, for example, was significantly linked to more GMV in a cluster of regions near the top of the brain including the superior parietal lobule and precuneus of the left hemisphere. Having had more children was significantly associated with more GMV in inferior and middle frontal gyri, and middle and inferior temporal gyri. Having used hormone replacement therapy was associated with more GMV in superior frontal gyrus and several other brain regions. All these brain regions are known to be affected by aging and Alzheimer’s.
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Low, rather than high testosterone and hyperestrogenism may favor prostate inflammation and benign prostate hyperplasia. (2019) www.sciencedirect.com
From the publication:
Mounting evidence shows that low, rather than high, T[estosterone] levels favor prostate inflammation and that hyperestrogenism also may play a role. Considering all these data, we postulate that BPH results from the actions of multiple factors occurring together or at different time points, which can reinforce and favor their mutual detrimental effects. The initial steps in this process are likely to occur early in life with an overt or subclinical prostatitis, probably influenced by infectious agents. The resulting prostatic inflammation could be amplified and maintained by metabolic derangements occurring in such conditions as MetS [metabolic syndrome]. Low T and the relative hyperestrogenism secondary to MetS [metabolic syndrome] could further exacerbate the immune process, leading to a chronic inflammation. When prostatitis becomes chronic, a number of cytokines are produced that act in the tissue to maintain the pathological condition. On the other hand, several growth factors are secreted, and their elevated concentrations lead to prostate remodeling and enlargement. The resulting mechanical obstruction and inflammatory damage are the basis of BPH and its associated urinary symptoms.
[…]
In addition, treating hypogonadism, which frequently accompanies MetS, not only is not detrimental for the prostate, but also could even be a therapeutic resource for relieving urinary symptoms and limiting the inflammatory process in the prostate.
[…]
The apparent contradiction of these results with the success of 5-alpha reductase inhibitors in treating LUTS merits closer investigation. Undoubtedly, treatment with 5-alpha reductase inhibitors results in a prostate volume decrease, which in turn translates into an improvement in LUTS. Nonetheless, it should be kept in mind that studies assessing intraprostatic androgen levels have linked 5-alpha reductase inhibition with a decrease in DHT and an increase in T.
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Antidepressants can affect testosterone and estrogen levels. (2021) www.sciencedirect.com
From the publication:
Firstly, according to the reviewed data from preclinical studies, SSRIs affect to a greater extent, both testosterone and estrogen serum levels compared to the rest of drug classes (Tables 1 and 3). In particular, more than 50% of the reviewed publications report changes in testosterone and estrogen levels after SSRI administration. The same conclusion cannot be drawn from the comparatively fewer studies that investigated other classes of monoaminergic antidepressants. Secondly, data indicated differences between acute and sub-chronic or chronic drug administration on testosterone and estrogen levels. On the one hand, acute antidepressant treatment either decreases or does not affect testosterone and estrogen levels. On the other hand, data from sub-chronic and chronic antidepressant treatment are conflicted, probably due to variable treatment duration and differences in the time and method of sampling. Furthermore, from our reviewed data it appears that testosterone levels are more frequently affected by antidepressants in comparison to estrogen. More specifically, the majority of studies found no changes in estrogen levels following drug administration, whereas the rest of the studies reported either increased or decreased levels of testosterone in both males and females (Tables 1 and 3). Unfortunately, inconsistencies in methods, i.e., inclusion of both sexes, doses, age, duration, and strain, as well as the technical difficulties in measuring low and variable estrogen levels account for the conflicting data and impede any firm conclusions.
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Low testosterone levels may be associated with risk of fracture in men over 60. (2008) www.sciencedaily.com
From the article:
Low-trauma fractures occurred in 113 men during follow-up with the risk of fracture significantly higher in those with low testosterone levels. “Twenty-five men experienced multiple incident fractures,” the authors note. “A total of 149 incident fractures were reported, including 55 vertebral, 27 hip, 28 rib, six wrist and 16 upper and 17 lower extremity fractures.”
“After adjustment for sex hormone binding globulin (a blood protein), serum testosterone and serum estradiol levels were associated with overall fracture risk,” according to the authors. “After further adjustment for major risk factors of fractures (age, weight or bone mineral density, fracture history, smoking status, calcium intake and sex hormone binding globulin), lower testosterone was still associated with increased risk of fracture, particularly with hip and non-vertebral fractures.”
Although low levels of estradiol and testosterone were associated with a higher risk of fracture in men over 60, only the effect of testosterone was independent of other risk factors, the authors conclude.
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Testosterone may need to be converted to estrogen in the brain to show anxiety- and depression-inhibiting effects, mouse study suggests. (2015) www.sciencedaily.com
From the article:
He already knew that testosterone had a protective effect on males, just as estrogen and progesterone do on females. He also knew that most testosterone was converted into estrogen in the brain. What he didn’t know was that those anxiety- and depression-inhibiting effects couldn’t be produced unless the testosterone was first converted to estrogen.
“There is an enzyme in the brain that ‘mediates’ the conversion of testosterone into estrogen,” Kabbaj said. “We inhibited that enzyme in a specific brain area implicated in the regulation of mood. And when you do that, you lose the antidepressant effect of testosterone. So the conversion is very important.”
His lab targeted the hippocampus area of the brain, where testosterone acts through what’s known as the MAPK pathway to induce its antidepressant and anti-anxiety effects.
“But we have to be careful about that pathway,” Kabbaj said, “because it’s also implicated in cellular growth and cancer. Therefore, we’re looking for other pathways that don’t have these effects. It’s complicated. Nothing is ever simple, but we’ll get there.”
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Testosterone predominance may increase the prevalence of metabolic syndrome during menopause. (2008) www.sciencedaily.com
From the article:
“Menopause-related testosterone predominance appears to be implicated as a key hormonal change that is associated with the incidence of metabolic syndrome,” said lead investigator Imke Janssen, PhD, assistant professor, Department of Preventive Medicine at Rush University Medical Center.
It was previously thought that estrogen exerted a direct positive effect on cardiovascular disease risk in women, a benefit that was lost as women transitioned from a premenopausal to a postmenopausal state and experienced a loss of estrogen.
“Our study data shows that the change in estrogen level is, at best, a weak and nonsignificant predictor of metabolic syndrome risk,” said Janssen. “A more likely story is that the progressive testosterone predominance exerts a direct negative effect on cardiovascular risk.”
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Female reproductive steroids provide anti-inflammatory and antibody production suggesting COVID-19 symptom protection. (2020) www.sciencedaily.com
From the article
Female reproductive steroids, estrogen and progesterone and its physiologically active metabolite, allopregnanolone, provide anti-inflammatory functions, reshape competence of immune cells, stimulate antibody production and promote respiratory epithelial cell repair, and inhibit the ACE2 receptor, the door of access for the novel coronavirus (SARS-CoV-2) to infect the organism, suggesting they may protect against COVID-19 symptoms, according to Pinna’s report. The paper is published in Trends in Endocrinology and Metabolism.
Pinna became interested in the role of reproductive steroids in COVID-19 pathology in March when early case reports showed COVID-19 positive pregnant women who had no COVID-19 symptoms, had escalated symptoms – severe enough to require intensive care – immediately after giving birth. The severity of symptoms coincided with a rapid drop of estradiol, progesterone, and allopregnanolone.
“Hormones that help sustain the pregnancy – like progesterone – are 100 times more concentrated in a pregnancy’s third trimester. Estradiol, allopregnanolone, and progesterone all have important anti-inflammatory functions and are involved in resetting the immune system. This suggests that pregnant women became symptomatic, and some were even admitted to the ICU, after delivering their babies because of the rapid drop in these hormones,” said Pinna. “The correlation was really striking.”
According to recent CDC data, in the United States, 38,071 women who were pregnant contracted COVID-19, with 51 deaths – 0.13%. For non-pregnant women, the death toll is 2%.
“Pregnant women are 15 times less likely to die from COVID than other women,” said Pinna.
Additionally, nutrition may also play a role when diets are enriched with phytoestrogens – plant-produced ‘estrogen’ – (in foods such as soybeans, lentils, oats). Phytoestrogens have the ability to bind directly to human estrogen receptors, or can be converted to estradiol by the microbiome.
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Estrogen improves symptoms in a mouse model of Parkinson's disease. (2019) www.sciencedaily.com
From the article
Estrogen is thought to protect movement neurons from Parkinson’s disease, but how is unknown. Since the patients more susceptible to Parkinson’s disease – men and post-menopausal women – have low estrogen levels, estrogen treatment might be an effective way to delay and reduce symptoms.
Silke Nuber and colleagues at Harvard Medical School treated mouse models of Parkinson’s disease with brain-selective estrogen and compared the motor performance of males and females before and after treatment. The female mice showed less severe symptoms at a later age, but estrogen still improved their symptoms. In male mice, the estrogen treatment reduced alpha-synuclein breakdown and buildup and helped with severe symptoms, suggesting that estrogen could be a viable treatment option for Parkinson’s patients with low estrogen levels.
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Estrogen mitigates the association between visceral fat on cognitive decline.
Estradiol, a form of estrogen, is the primary female sex hormone. It participates in menstrual cycle regulation and drives the development of female secondary sex characteristics, such as breasts, a wider pelvis, and gynoid fat – fat that forms around the hips, thighs, and breasts. Evidence suggests that estradiol exerts both cardioprotective and neuroprotective effects. Findings from a 2020 study demonstrate that estradiol mitigates the association between visceral fat on cognitive decline.
Cognitive decline is characterized by altered brain structural networks and accelerated degeneration with aging. Scientists don’t fully understand the biological mechanisms that drive cognitive decline, but evidence indicates that visceral fat – a type of fat that accumulates in the abdominal cavity – may play a role. Visceral fat is metabolically active and is associated with increased markers of inflammation and oxidative stress, and decreased levels of anti-inflammatory proteins, such as adiponectin
The cross-sectional study involved 974 cognitively healthy females and males (average age, ~50 years). Using magnetic resonance imaging, the investigators measured the participants' gray matter volume, cerebral cortex area, intracranial blood vessels, and visceral fat. They also measured estradiol concentrations in a subset (390) of the females. All the participants completed neuropsychological testing to assess memory performance.
The investigators found that visceral fat exacerbated the harmful effects of aging on the brain’s structural networks in both females and males. However, estradiol mitigated some of these effects in the females, but not the males. Females between the ages of 35 and 55 years (the period surrounding menopause) who had lower estradiol concentrations were more likely to exhibit greater structural network impairments and worse memory performance.
These findings suggest that estradiol mitigates some of the harmful effects of visceral fat on the brain’s structural networks and cognitive health. Interestingly, the fasting-mimicking diet preferentially depletes visceral fat. Learn more in this clip featuring Dr. Valter Longo.
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Estrogen may provide protection against Alzheimer's disease. medicalxpress.com
Scientists have long known that estrogen, the primary female sex hormone, exerts protective effects on multiple organ systems. For example, estrogen helps maintain healthy blood lipid levels, reduces the risk of cardiovascular disease, and promotes bone health. Findings from a recent study suggest that estrogen protects against age-related cognitive decline and Alzheimer’s disease.
Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. The disease disproportionally affects women, and scientists have identified distinct sex-related differences in Alzheimer’s disease symptoms, progression, biomarkers, and risk factors. Interestingly, the pathological hallmarks of Alzheimer’s disease begin to appear 10 to 20 years before the onset of symptoms – roughly coinciding with the period of menopause in women.
The study involved 99 women and 29 men (average ages, 52 years) who were cognitively normal. The women provided information about their reproductive histories, such as when they began menstruating, how many pregnancies they had, when they experienced menopause, and whether they had used hormonal contraceptives or hormone replacement therapy. Both women and men underwent memory testing and brain scans.
The scans revealed that the women who were peri- or postmenopausal had less gray matter volume in the temporal cortex, an area of the brain vulnerable to the effects of Alzheimer’s disease. Women who were premenopausal or had longer estrogen exposure due to their reproductive histories were more likely to have greater gray matter volumes. Exposure to estrogen did not influence performance on the memory tests directly, but participants with greater gray matter volume tended to perform better than those with lower volume.
These findings suggest that estrogen exposure exerts protective effects on brain health and illuminate the need for sex-specific research on Alzheimer’s disease pathology and therapies. This was a small study, however, and only identified associations between estrogen exposure and brain health, not causes.
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Sugar exposure reduces production of sex hormone-binding globulin, a predictor of metabolic health. www.sciencedaily.com
Obesity and metabolic disease are associated with reduced fertility and alterations in several markers of reproductive health, including plasma concentrations of sex hormone-binding globulin. Low levels of sex hormone-binding globulin are common in those with obesity and are predictive of cardiovascular disease and type 2 diabetes risk, although it is unclear how glucose and insulin regulation affect sex hormone-binding globulin levels. A group of investigators recently performed a series of experiments with the aim of identifying mechanisms of sugar metabolism and sex hormone-binding globulin production.
Sex hormone-binding globulin, which is produced by liver, transports sex hormones in the blood and regulates their uptake by sensitive tissues. Hepatocyte nuclear factor-4α, also produced by the liver, stimulates sex hormone-binding globulin production and increases serum testosterone by decreasing its half-life. De novo lipogenesis, the process by which the liver converts excess sugar into fatty acids, suppresses hepatocyte nuclear factor-4α activation and sex hormone-binding globulin production.
In the first experiment, the researchers used transgenic mice whose genomes had been altered to express the human sex hormone-binding globulin gene. They fed these mice a diet high in either sucrose, glucose, or fructose (three types of simple sugars) for one week and measured blood levels of sex hormone-binding globulin. In a second experiment, the researchers exposed human liver cells to varying amounts of insulin and to high concentrations of either glucose or fructose and measured gene expression. Finally, they exposed the same type of liver cells to varying concentrations of glucose and fructose and to the fatty acid palmitate and measured gene expression.
After five days a high fructose diet reduced sex hormone-binding globulin levels in the mice by fructose 80 percent. Sex hormone-binding globulin levels decreased by 40 percent on a high glucose diet and 50 percent on a high sucrose diet. Insulin exposure did not affect sex hormone-binding globulin production in mice. In liver cells, glucose and fructose exposure over five days reduced sex hormone-binding globulin accumulation by 50 percent. This change corresponded to a three- to fourfold reduction in the expression of hepatocyte nuclear factor-4α. Additionally, glucose or fructose exposure over five days resulted in a two- to threefold increase in palmitate production (due to de novo lipogenesis), which corresponded to reductions in sex hormone-binding globulin. Finally, exposure to varying amounts of palmitate over five days reduced hepatocyte nuclear factor-4α expression and sex hormone-binding globulin production.
The authors of this comprehensive study concluded that excess sugar intake resulted in increased de novo lipogenesis, which led to a suppression of hepatic HNF-4α activity, which in turn attenuated sex hormone-binding globulin expression. This work provides a detailed explanation of why sex hormone-binding globulin is a sensitive biomarker of metabolic syndrome and why simple sugars, especially fructose, decrease fertility.
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Why is Stem Cells Therapy Good for Anti Aging? - Stemfinitycord Malaysia stemfinitycord.co
Stem cell therapy is a type of cell therapy where stem cells are introduced into the damaged tissue to treat the disorder or the injury. Mesenchymal stem cells (MSCs) are used in most stem cell therapy. They’re non-hematopoietic cell precursors initially found in the bone marrow, but actually present in many other tissues. Mesenchymal stem cells (MSCs) in culture are adherent, proliferating, and capable of multilineage differentiation into several tissues of mesenchymal origin, such as bone marrow stroma, adipose tissue (body fat), bone, cartilage, tendon, skeletal muscle and etc.
So Why is Stem Cells Therapy Good for Anti Aging?
In short, stem cells therapy was heavily emphasised to have the capacity to repair, renew and replace damaged tissue is a good anti aging treatment.
As shown below are the functions of Mesenchymal stem cells (MSCs) therapy: - Help facilitate growth of new blood vessels, a process known as angiogenesis which leads to improved blood flow in tissue - An anti-inflammatory effect which fastens wound healing - After aiding wound healing, it helps in reducing size of scarred tissue such as infected cardiomyocytes (heart cells) or wound to joint injury - Repair of damaged tissue which then leads to renewal of healthy tissue - Relief if symptoms related to any chronic diseases - Vast improvement in the immune system against disease - Better digestion and elimination of constipation - More flexible joints and discs - Improvement in skin elasticity and thickness - Reducing facial pigmentation, and adding a glow to your skin - Diminishing fine lines and wrinkles - Improving skin complexion - Tightening and shrinking open pores - Removing dark circles
No more joints problems, no more constipation, better appearance, overall human health improves!
The list is non-exhaustive when it comes to stem cells therapy. All these benefits brought by stem cells therapy are exactly the definition of anti aging if not reviving old age.
Visit more information on: http://stemfinitycord.co/