Neural Origins Of Hot Flashes In Menopausal Women Identified By Study

Dr. Enrique Jacome

A study from neuroscientists at the Wayne State University School of Medicine provides the first novel insights into the neural origins of hot flashes in menopausal women in years. The study may inform and eventually lead to new treatments for those who experience the sudden but temporary episodes of body warmth, flushing and sweating.

The paper, "Temporal Sequencing of Brain Activations During Naturally Occurring Thermoregulatory Events," by Robert Freedman, Ph.D., professor of psychiatry and behavioral neurosciences, founder of the Behavioral Medicine Laboratory and a member at the C.S. Mott Center for Human Growth and Development, and his collaborator, Vaibhav Diwadkar, Ph.D., associate professor of psychiatry and behavioral neurosciences, appears in the journal Cerebral Cortex, an Oxford University Press journal.

"The idea of understanding brain responses during thermoregulatory events has spawned many studies where thermal stimuli were applied to the skin. But hot flashes are unique because they are internally generated, so studying them presents unique challenges," said Freedman, the study's principal investigator. "Our participants had to lie in the MRI scanner while being heated between two body-size heating pads for up to two hours while we waited for the onset of a hot flash. They were heroic in this regard and the study could not have been conducted without their incredible level of cooperation."

"Menopause and hot flashes are a significant women's health issue of widespread general interest," Diwadkar added. "However, understanding of the neural origins of hot flashes has remained poor. The question has rarely been assessed with in vivo functional neuroimaging. In part, this paucity of studies reflects the technical limitations of objectively identifying hot flashes while symptomatic women are being scanned with MRI. Nothing like this has been published because this is a very difficult study to do."

During the course of a single year, 20 healthy, symptomatic postmenopausal women ages 47 to 58 who reported six or more hot flashes a day were scanned at the School of Medicine's Vaitkevicius Imaging Center, located in Detroit's Harper University Hospital.

The researchers collected skin conductance levels to identify the onset of flashes while the women were being scanned. Skin conductance is an electrical measure of sweating. The women were connected to a simple circuit passing a very small current across their chests, Diwadkar said. Changes in levels allowed researchers to identify a hot flash onset and analyze the concurrently acquired fMRI data to investigate the neural precedents and correlates of the event.

The researchers focused on regions like the brain stem because its sub regions, such as the medullary and dorsal raphe, are implicated in thermal regulation, while forebrain regions, such as the insula, have been implicated in the personal perception of how someone feels. They showed that activity in some brain areas, such as the brain stem, begins to rise before the actual onset of the hot flash.

"Frankly, evidence of fMRI-measured rise in the activity of the brain stem even before women experience a hot flash is a stunning result. When this finding is considered along with the fact that activity in the insula only rises after the experience of the hot flash, we gain some insight on the complexity of brain mechanisms that mediate basic regulatory functions," Diwadkar said.

These results point to the plausible origins of hot flashes in specific brain regions. The researchers believe it is the first such demonstration in academic literature.

They are now evaluating the network-based interactions between the brain regions by using more complex modeling of the fMRI data. "We think that our study highlights the value of using well-designed fMRI paradigms and analyses in understanding clinically relevant questions," Diwadkar said.

The researchers also are exploring possibilities for integrating imaging with treatment to examine whether specific pharmacotherapies for menopause might alter regional brain responses.

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Research Reveals New Details About The Receptor Mechanisms Of Estrogen's Role In Memory

Dr. Enrique Jacome

In a new study, Karyn Frick, professor of psychology at the University of Wisconsin-Milwaukee (UWM), uncovers details about estrogen's role in the complex cellular communication system underlying memory formation.

"The receptor mechanisms that regulate estrogen's ability to enhance memory are still poorly understood," says Frick. "With this study, we've begun to sort out several of the key players needed for estrogens to mediate memory formation."

The research, published in the the Journal of Neuroscience, 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. Collectively, the data provide the first evidence that the rapid signaling initiated by such interactions is essential for estradiol to enhance memory regulated by the hippocampus.

"Our data suggesting that interactions between estrogen receptors and mGluR1 at the cell membrane are critical for estradiol to enhance memory provides important new information about how estrogens regulate memory formation," Frick says.

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Study Shows Joint Symptoms In Postmenopausal Women Not Reduced By Calcium Plus Vitamin D Supplementation

Dr. Enrique Jacome

A team of investigators systematically analyzed the effect of calcium and vitamin D supplementation on joint symptoms in a rigorous and controlled study of postmenopausal women. They found that supplementation did not reduce the severity of joint symptoms reported by the participants. Their results are published in the Journal of the Academy of Nutrition and Dietetics.

The influence of low calcium and vitamin D deficiency on joint symptoms has been studied with mixed results. Only some observational studies have associated vitamin D with knee osteoarthritis and results from full-scale randomized trials have been sparse. "In the current study, we addressed for the first time in a full-scale, randomized clinical trial setting, the clinically relevant question of whether postmenopausal women using calcium and vitamin D supplements in currently recommended dosage would experience any favorable effect on joint pain or swelling, common symptoms in postmenopausal women," says lead investigator Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, California.

Using data from the Women's Health Initiative (WHI) calcium plus vitamin D supplementation trial, researchers identified a subgroup of 1,911 postmenopausal women for the current study, who had been randomized to receive calcium carbonate with vitamin D3 daily or placebo and had undergone serial joint symptom assessment. Responses to a questionnaire provided qualitative information on joint pain and joint swelling before entry and two years after randomization.

Between the daily supplement use and placebo groups, joint pain and swelling at baseline entry was comparable, at more than 70 percent. After two years, analysis revealed no statistically significant difference for the frequency or severity of joint pain or swelling.

The research team also evaluated data to determine the potential for interaction with age, BMI(body mass index), physical activity, non-protocol calcium and vitamin D supplement use, race/ethnicity, and hormone therapy. Investigators found no interaction with age, BMI, race/ethnicity, or physical activity. No significant interaction was evident with non-protocol vitamin D supplement use at entry. However, participants using non-protocol calcium supplements at entry reported less joint pain compared with those in the placebo group. The influence of calcium and vitamin D supplementation individually on joint symptoms was not determined because both were provided combined in a single pill in this trial.

Dr. Chlebowski concludes, "Joint symptoms are relatively common in postmenopausal women. 

However, daily supplementation with 1,000 mg of calcium carbonate and 400 IU of vitamin D3 in a randomized, placebo-controlled clinical trial setting did not reduce the self-reported frequency or severity of joint symptoms."

Dr. Chlebowski and his team add that these findings do not speak against current recommendations for vitamin D intakes for bone health and fracture risk reduction. 

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Study Shows That Exercise Is Good For Women, But It Won't Cut Hot Flashes

Dr. Enrique Jacome

Exercise has proven health benefits, but easing hot flashes isn't one of them. After participating in a 12-week aerobic exercise program, sedentary women with frequent hot flashes had no fewer or less bothersome hot flashes than a control group. This randomized, controlled study from the MsFLASH Research Network was published in Menopause, the journal of The North American Menopause Society.

The 248 women in the trial were either approaching menopause or were postmenopausal; 142 of them continued to go about their usual activities, and 106 participated in aerobic exercise training three times a week for 12 weeks at a fitness center. All the women kept daily diaries on their hot flashes and night sweats and on how well they slept and also completed questionnaires about insomnia, depression, and anxiety.

Although exercise had small positive effects on sleep quality, insomnia, and depression, it had no significant effect on hot flashes for the women overall. Race and initial fitness did make some difference, however. White women in the exercise program did show improvement in their hot flashes compared with white women who maintained their usual activity level, but there was no similar difference among African-American women. Also, women who were more fit to begin with had greater improvement in their hot flashes with exercise.

The study helps to settle a debate about the effect of exercise on hot flashes. Previous studies have been inconsistent, but this study corroborates a recent Cochrane review on the topic, which concluded that there was no evidence to support the use of exercise as an effective treatment for hot flashes and night sweats.

"Midlife women cannot expect exercise to relieve [hot flashes and night sweats] but may reasonably expect it to improve how they feel and their overall health," said the investigators.

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Study Shows That Estrogen May Influence Location Of Women's Fat

Dr. Enrique Jacome

Ever wondered why some women, but not all, have the "pear" shape considered by many to be desirable? Researchers might have found some answers to the mystery, after discovering that estrogen, one of the sex hormones, affects where fat is stored in a woman's body.

The study was conducted by researchers from East Carolina University and published in the American Journal of Physiology: Endocrinology and Metabolism. It involved 17 premenopausal women ages of 18 and 44 who were overweight or obese.

Researchers  asked the women to provide:

• Weight
• Height
• Fat percentage
• Lean body mass
• VO2 max (a measure of physical fitness).

They then analyzed how estrogen affects fat accumulation in particular areas of the body.

This was done by slowly infusing estrogen into the buttocks and belly of the women overnight. The women were then given drugs that encouraged the burning of fat in the body (lipolysis). They were also asked to exercise at a level similar to a standard exercise session, both with and without the lipolysis drugs.

Fat breakdown was measured using microdialysis - a sampling technique that looks for the amount of glycerol left behind after the breakdown of fat for eventual energy production.

The researchers found that the effect of estrogen on fat deposits was dependent on the deposits' particular location and how the fat is burned.

Results of the study revealed that estrogen halted fat breakdown in the abdomen area when the hormone was infused alongside a lipolysis drug called isoproterenol. However, it did not have the same effect in the buttocks.

The researchers add that after a second drug was infused in the abdomen along with the first, no further fat was broken down.

But when both of the fat-mobilizing drugs were infused together alongside exercise, and when the participants exercised without the drugs, fat breakdown in the abdomen increased, although less in the buttocks.

The study authors say: "Our results indicate that the influence of E2 (estrogen) is dependent on the adipose tissue (loose connecting tissue) depot of interest as well as the specific regulatory mechanism targeted.

The authors add: 

"The importance of understanding estrogen action in adipose tissue is underscored by the fact that adipose tissue is an estrogen-producing organ, particularly in postmenopausal women, where adipose tissue is the major site of estrogen production."

The scientists say their findings could potentially lead to an understanding of why post-menopausal women are more likely to accumulate fat around the abdomen area.

When it comes to pre-menopausal women, the researchers say that the relationship between estrogen and the breakdown of fat is what may help maintain a woman's "pear" shape - more fat around the middle area of the body.

They conclude that further research is needed to determine the mechanisms as to why and how the effects of estrogen vary.

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Recognizing Menopausal Symptoms Is The First Step

Dr. Enrique Jacome

When I ask patients to give me a definition of menopause, I receive a variety of answers that consist of “When you get hot flashes” to “Not having a period for over a year”.  Many women go under diagnosed because of the failure of physicians to apply a scientific method for diagnosis. 

Scientifically, a diagnosis is when the level of follicle stimulation hormone (FSH) reaches a level greater than 23 miu/ml, whether she is menstruating or not. Peri-menopause typically begins when a woman is in her 40’s and can average 4 to 8 years.  Menopause occurs roughly in women their early 50’s. Every year it is estimated that 1.3 million women are expected to reach menopause.

I will take you through a series of symptoms that a woman should look for and what should she do next.  NO woman should ever have to suffer through any symptom(s) nor feel less than a woman.  Menopause is a natural part of the aging process.  Not all symptoms will show in all women.  Please use this as a guide only.

During the menopausal transition women may experience sexual dysfunction as well as depressive symptoms.  Due to the loss of estrogen, one’s symptoms can also consist of:

• Hot flashes
• Severe sweating – can happen both day and night
• Insomnia
• Vaginal dryness
• Vaginal discomfort
• Irritability
• Loss of memory or fuzzy thinking
• Cold sweats
• Irregular periods
• Anxiety
• Mood swings
• Headaches
• Sadness

When a woman comes to me with symptoms, as previously stated, I take the time to listen to what each individual patient is telling me, never discounting any of their feelings or symptoms.  My immediate instinct as a Doctor is to help her improve her symptoms and get her on the right track to feeling like a woman again.  My first recommendation is that they have a simple blood test that will measure their pituitary hormone Follicle Stimulating Hormone (FSH) level. Depending upon the blood work I get back from their testing’s, my suggested and most successful form of hormone replacement would be via the Pellet Hormone Delivery System (PHDS). Women who have their hormones replaced via PHDS allows the body to recreate a continuous flow of hormones that the ovaries normally and previously produced within their bodies.  This method of delivery is more important than any other type of replacement therapy as it is surgically inserted and allows the body to control the release of the hormones over time.  Nothing in an oral, patch or cream can reproduce the normal hormone correction that is needed.

Always remember to go with your instinct regarding how you are feeling and if you are displaying some of the symptoms above, as each woman knows best how they should feel and seek the advice of a doctor.  Don’t ever give in or give up to the ugly face of menopause.

Remember to put your fears away, as life during and after menopause can be quite enjoyable!

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Urinary Infection During Menopause Treated With Estrogen In Mouse Study

Dr. Enrique Jacome

Estrogen levels drop dramatically in menopause, a time when the risk of urinary tract infections increases significantly. 

Researchers at Washington University School of Medicine in St. Louis have found new evidence in mice that the two phenomena are connected by more than just timing. If further research confirms these links, boosting estrogen levels may get a second look as an approach for reducing urinary infections in menopausal women. 

"Scientists tested estrogen as a treatment for post-menopausal women with urinary tract infections in the 1990s, but the results were either ambiguous or negative," says senior author Indira Mysorekar, PhD, assistant professor of obstetrics and gynecology and of pathology and immunology. "With the mouse model of menopause that we've created, we can more completely understand how estrogen levels affect infection susceptibility, bladder health and the inflammatory response to infection. That should point the way to better treatment strategies." 

The findings appear online in Infection and Immunity. 

Urinary infections are a significant cause of illness in many women throughout their lives and are particularly prevalent after menopause. The bacteria that cause these infections can spread to the kidney and bloodstream, with the potential for serious complications. 

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. 

Mysorekar notes that earlier clinical trials of estrogen's usefulness against urinary infection evaluated the treatment's success by tracking levels of bacteria in the urine. The researchers say their new results suggest that bacteria levels alone may not provide a complete picture of estrogen's effectiveness against the infections. 

"If we can find ways to look at other aspects of the infectious process in humans, we may find that estrogen is more helpful than we previously realized," Mysorekar says. "We need to look for other indicators, such as cytokines in the urine, to more fully assess estrogen's potential role in treatment." 

www.vivenaturalhormones.com