Estrogen helps brain keep weight in check
Posted by on November 3, 2011 - 2:44pm

A recent UT Southwestern Medical Center study found that estrogen regulates energy expenditure, appetite and body weight, while insufficient estrogen receptors in specific parts of the brain may lead to obesity.

“Estrogen has a profound effect on metabolism,” said Dr. Deborah Clegg, associate professor of internal medicine and senior author of the study published Oct. 5 in Cell Metabolism. “We hadn’t previously thought of sex hormones as being critical regulators of food intake and body weight.”

The mouse study is the first to show that estrogen, acting through two hypothalamic neural centers in the brain, keeps female body weight in check by regulating hunger and energy expenditure. Female mice lacking estrogen receptor alpha – a molecule that sends estrogen signals to neurons – in those parts of the brain became obese and developed related diseases, such as diabetes and heart disease.

Similar results were not seen in male mice, although researchers suspect other unknown estrogen receptor sites in the brain play a similar role in regulating metabolism for males as well. Estrogen receptors are located throughout the body, but researchers found two specific populations of estrogen receptors that appear to regulate energy balance for female mice.

The findings are potentially important for millions of postmenopausal women, many of whom have decided against hormonal replacement therapy. The study could lead to new hormonal replacement therapies in which estrogen is delivered to specific parts of the brain that regulate body weight, thereby avoiding the risks associated with full-body estrogen delivery, such as breast cancer and stroke.

Doctors stopped routinely recommending long-term estrogen therapy for menopausal women in 2002 when a Women’s Health Initiative study showed the hormone did not prevent heart disease in women who already were at increased risk.

“The role of estrogen in postmenopausal women continues to remain uncertain,” Dr. Clegg said. “Current research is focused on the timing and the type of estrogen supplementation that would be most beneficial to women. Our findings further support a role for estrogens in regulating body weight and energy expenditure, suggesting a benefit of estrogen supplementation in postmenopausal women.”

Source: UT Southwestern Medical Center

 

Menopause management complex but possible!
Posted by on October 7, 2011 - 6:10am

Recently, I attended the meeting of the North American Menopause Society (NAMS) in Washington DC along with 1500 other health professionals.    The bottom line:    Estrogen is not the devil, but it is not the panacea for all things female!

When the large Women's Health Initiative was halted in 2002 due to some unexpected findings in women on hormone treatment, the use of hormones significantly dropped.   However, many women found that their most bothersome symptoms returned and some went back on HT with a bit more concern.

The conference focused on new data, much of it refined to look at subsets of women.   It has become significantly clearer that all women are NOT alike when it comes to their health status at the time menopause begins, their age at onset, and the intensity of symptoms. Thus, generalizing outcomes to all women makes little sense.

Here are a few key points that were discussed at the meeting and are currently being studied by researchers:

  • Ill effects in the WHI  participants were more predominant in women who were 10 years post menopause when it came to heart disease.    The latest research suggests that estrogen can make atherosclerosis (one cause of heart disease) worse in women who already have it, but it may delay or prevent it in women who still have healthy arteries.
  • There is an increased risk of breast cancer in hormone users but the absolute numbers were small and were more prevalent among those who took HR that contained both estrogen and progesterone.   Women on estrogen alone had risks similar to placebo.   There is growing interest in the role certain types of progesterone  used in combination therapy play in breast cancer risk.
  • There is a major concern about osteoporosis and bone fractures among aging women whose estrogen levels are dropping.   As one researcher put it, "breaking a hip (in older women) can  kill you faster than breast cancer".   Approximately 50% of women over age 50 will have at least one fracture and we know that hormone therapy significantly reduces that risk. Understanding personal risk profiles for these two conditions should be part of the decision process.
  • While there are more drugs on the market to help maintain bone health, there is more long term data available  on their use that is indicating some alarming side effects with prolonged use. Some of these side effects may be worse than those related to hormone therapy.
  • Researchers are finding that the stages of the menopause transition are quite complex and there may be several levels of the transition that may need different interventions.
  • Vaginal atrophy in women including breast cancer survivors  can be devastating and reasonable treatment options are sorely needed.
  • Since the WHI, there are new treatment options available today for menopause symptoms using different drug formulas and different means of applications (pills, patches, creams, gels and sprays) that may have reduced risk profiles.

That's just a sampling of the many topics discussed at this conference.    Our Institute has been awarded a grant from the Evergreen Initiative at Northwestern Memorial Hospital Foundation to create a decision making tool for women who are menopausal and having bothersome symptoms.    As a result, we will be focusing on all aspects of menopause this year through our educational and fact finding events and I encourage you to follow our blog for our latest findings.

Why has Menopause Management become so Controversial?
Posted by on March 8, 2011 - 11:59am

Women, on average, live one-third of their lives post menopause.   Some women find menopause an easy transition. Other women are chronically bothered by persistent hot flashes and night sweats that impact their quality of life.   For years, hormone therapy was the answer but it has been shadowed by controversy as researchers learn more about estrogen and its long term impact on the body.    The Institute for Women's Health Research discussed this controversy in its March e-newsletter that is available at  ENewsletter March 2011final.

Hormone Therapy and Breast Cancer Risk
Posted by on February 10, 2011 - 2:24pm

Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

Women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later. The finding, from the Million Women Study (MWS)—a large observational study in the United Kingdom—adds to a growing body of evidence that the use of combined hormone therapy (estrogen plus progestin) to treat menopausal symptoms increases the risk of breast cancer and deaths from the disease. The results appeared in the Journal of the National Cancer Institute on January 28.

The pattern of increased breast cancer risk “was seen across different types of hormonal therapy, among women [in the MWS] who used hormonal therapy for either short or long durations, and also in lean and in overweight and obese women,” Dr. Valerie Beral of Oxford University and her colleagues wrote. Their findings support results from the Women’s Health Initiative (WHI), a randomized clinical trial that, in 2002, first reported evidence linking combined hormone use to breast cancer.

“The new findings underscore the idea that there’s really no safe window of time for women to take combined hormone therapy,” said Dr. Leslie Ford of NCI’s Division of Cancer Prevention and the Institute’s WHI liaison. After the initial WHI results were announced, she noted, some people had argued that hormones may be safer when started at the time of menopause. “The new findings refute that argument,” she added.

WHI and MWS investigators have both reported that breast cancer incidence rates declined rapidly once women stopped taking combined hormone therapy. “It is important for women to know that if they stop using hormones, the risk of breast cancer very quickly returns to where it was before hormone therapy began,” Dr. Ford said.

There has been a discrepancy between the WHI and MSW results to date as to whether estrogen-only therapy raises breast cancer risk in postmenopausal women. WHI reports have found little risk associated with this treatment, whereas the MWS investigators have observed a statistically significant increased risk.

Additional follow-up from the WHI estrogen-only intervention trial should help clarify this issue in the coming years, noted Drs. Rowan T. Chlebowski of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Garnet L. Anderson of the Fred Hutchinson Cancer Research Center in an accompanying editorial.

Does Estrogen Make You Smarter?
Posted by on November 26, 2010 - 10:17am

Scientists discover how estrogen works and flip its switch to reap benefits without risks

CHICAGO --- Estrogen is an elixir for the brain, sharpening mental performance in humans and animals and showing promise as a treatment for disorders of the brain such as Alzheimer’s disease and schizophrenia. But long-term estrogen therapy, once prescribed routinely for menopausal women, now is quite controversial because of research showing it increases the risk of cancer, heart disease and stroke.Northwestern Medicine researchers have discovered how to reap the benefits of estrogen without the risk. Using a special compound, they flipped a switch that mimics the effect of estrogen on cortical brain cells. The scientists also found how estrogen physically works in brain cells to boost mental performance, which had not been known.

When scientists flipped the switch, technically known as activating an estrogen receptor, they witnessed a dramatic increase in the number of connections between brains cells, or neurons. Those connections, called dendritic spines, are tiny bridges that enable the brain cells to talk to each other.

“We created more sites that could allow for more communication between the cells,” said lead investigator Deepak Srivastava, research assistant professor in neuroscience at Northwestern University Feinberg School of Medicine. “We are building more bridges so more information can go from one cell to another.”

Previous research has shown an increase in dendritic spines improves mental performance in animals. In humans, people who have Alzheimer’s disease or schizophrenia often have a decrease in these spines.

“We think there is a strong link between the number of dendritic spines and your mental performance,” Srivastava said. “A major theory is if you increase the number of spines, it could be a way to treat these significant mental illnesses. “

Northwestern scientists also found strong clues that estrogen can be produced in cortical brain cells. They identified aromatase, a critical protein needed to produce estrogen, to be in precisely the right spot in the brain cell to make more dendritic spines.

“We’ve found that the machinery needed to make estrogen in these brain cells is near the dendritic spines,” Srivastava said. “It’s exactly where it’s needed. There’s a lot of it in the right place at the right time. “

Next, Srivastava said, he wants to further identify the key molecules involved in the dendritic spine production and target them in the same way as the estrogen receptor in order to ultimately be able to treat schizophrenia and other mental disorders.

Nick Brandon, head of psychiatry at Pfizer Inc., whose group collaborated with the Penzes lab for this work, added, “We are very excited by the emerging data in this area. There is a great deal of literature and precedent for a role of estrogen and estrogen signaling in major mental illnesses. This adds to our understanding of the specific neuronal functions. As we understand the effects of these specific estrogen receptor beta compounds in preclinical models, we are discovering effects on specific neuronal functions, which could be relevant for the treatment of cognitive disorders, depression and schizophrenia. “

Marla Paul is the health sciences editor. Contact her at marla-paul@northwestern.edu

Post-menopausal Estrogen Therapy may Increase Kidney Stone Risk
Posted by on October 25, 2010 - 11:49am

Researchers at the University of Texas Southwestern Medical Center report that estrogen therapy after menopause increases a woman's chances of developing kidney stones.  Kidney stones are common among postmenopausal women, affecting between 5% and 7% of the population in the U.S.  Up until now, only observational studies have been done looking at kidney stones and estrogen, and the results have been conflicting.   This study shows new evidence based on a randomized, placebo-controlled trial.

Lead study author, Dr. Naim Maalouf and colleagues conducted trials at 40 U.S. clinical centers where a total 10,739 post-menopausal women with hysterectomies and 16,608 post-menopausal women without hysterectomies were randomized to receive either an estrogen supplement or a placebo. Among those receiving hormones, 335 cases of kidney stones were reported versus 284 cases in the placebo groups.  In general, kidney stones are less common among pre-menopausal women than among men in the same age group, but the disparity lessens after menopause, suggesting that estrogen may have a protective effect.

However, study lead author Maalouf points out the study challenges the belief estrogen may protect against kidney stones.   "This research suggests that the opposite might be true, and it offers new information that might be considered when prescribing estrogen-replacement therapies to post-menopausal women," Maalouf says in a statement.

The study did not detect any link between kidney stone risk and body mass index, age, prior hormone therapy, coffee usage, diuretic usage, or ethnicity.

The exact mechanisms for these findings are yet to be determined.

Source:   Archives of Internal Medicine, October 11, 2010.