Groundbreaking Study Reveals Increased Estrogen Receptors in Menopausal Brains

Contrary to prior beliefs, estrogen receptors in the brain increase during menopause—a revelation that offers new insights into women’s brain health.

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For the first time, scientists have successfully measured estrogen activity in the human brain, offering new insights into how menopause affects women’s brain health.

Dr. Lisa Mosconi and her team at Weill Cornell Medicine used advanced brain imaging to reveal that, contrary to prior beliefs, estrogen receptors (ERs) in the brain increase during perimenopause and postmenopause.

These findings could change the approach to diagnosing and treating menopausal symptoms, suggesting that the window for effective estrogen therapy might be wider than previously assumed.

The Study: Measuring Brain Estrogen Activity

Published in Scientific Reports on June 20, the study utilized positron emission tomography (PET) imaging with a tracer that binds to estrogen receptors. Previously used only in oncology, this method allowed researchers to observe the density of estrogen receptors in the brains of 54 healthy women aged 40 to 65.

The PET scans revealed that women’s brains have more estrogen receptors as they go through menopause. As estrogen levels drop, the brain compensates by increasing the number of these receptors. This increase is particularly noticeable in postmenopausal women, whose brain scans showed more intense colors, indicating a higher density of estrogen receptors compared to premenopausal women.

“Using this method, we were able for the first time to measure ER activity in the brain, and to identify potential predictors of some of these common symptoms of menopause,” Dr. Mosconi, director of the Women’s Brain Initiative at Weill Cornell Medicine, said in a statement.

The increase in receptors, especially in areas of the brain related to thinking and memory, correlates with poorer memory performance and mood swings in postmenopausal women. Essentially, the brain is trying to capture as much estrogen as possible during this hormonal transition, which can lead to these cognitive and emotional symptoms.

“Blood tests are inadequate predictors of menopausal symptoms—or even if a woman is in menopause in the first place,” Dr. Mosconi wrote on her Instagram page. “Instead, brain ER levels predicted menopausal status with 100% accuracy and with symptoms such as low mood, memory lapses and reduced focus (aka ‘brain fog’).”

“This study completely changes our understanding of what is happening in the female brain with regard to hormone receptors,” Jaclyn Piasta, a board-certified women’s health nurse practitioner specializing in menopause, told The Epoch Times. “Previously, we have based our knowledge on rodent studies. The problem with this is that mice experience a very different menopause than humans.”

In rodent studies, estrogen receptor sites diminish and downregulate in menopause, but Dr. Mosconi’s study found that human brains actually upregulate these receptors by as much as 30 percent in some brain regions during menopause, she explained.

Menopause and Estrogen

During menopause, a woman’s body experiences significant hormonal changes, especially in estrogen levels. This essential hormone, which regulates various bodily functions, decreases sharply during this transition. According to Johns Hopkins Medicine, this decline is responsible for many symptoms associated with menopause.

A study published in The Journal of Clinical Endocrinology & Metabolism found that declining estrogen levels during menopause are linked to increased risks of cognitive decline and mood disturbances.

The study noted that women are particularly vulnerable to these changes during the perimenopausal and postmenopausal stages, when symptoms such as depression and anxiety are common.

In an interview in Maria Shriver’s Sunday Paper, Dr. Mosconi emphasized that understanding estrogen’s role in the brain during menopause goes beyond simply measuring hormone levels. What really matters, she explained, is how estrogen binds to its receptors, which are crucial for decoding the hormone’s messages.

Estrogen receptors are proteins in the brain that bind to estrogen, allowing it to exert its effects. They act as the brain’s way of reading these hormonal signals, dictating needs such as increased neuroplasticity, energy, blood flow, immunity, and connectivity.

The ability to examine estrogen receptors in the brain and their relationship to estrogen was previously unavailable. Dr. Mosconi’s team developed a tracer to visualize estrogen activity in the brain for the first time, revealing that the abundance and behavior of these receptors are as crucial as hormone levels themselves.

“I always remind women that hormones need receptors in order for them to work,” Dr. Corrine Menn, a board-certified obstetrician, gynecologist, and menopause expert, said on Instagram.

New Insights for Treatment

The new research offers promising implications for treating menopausal symptoms and could inform more targeted hormone replacement therapies (HRT). Personalized HRT plans could better address symptoms such as memory lapses, mood swings, and “brain fog” by considering the brain’s hormonal environment.

According to the North American Menopause Society, hormone replacement therapy is used to relieve menopause symptoms by replenishing declining levels of estrogen and sometimes progesterone. Women take HRT to manage symptoms such as hot flashes, night sweats, mood swings, vaginal dryness, and to reduce the risk of osteoporosis.

Dr. Mosconi highlighted in the press release that the persistence of estrogen receptors in the brain up to a decade after menopause suggests estrogen therapy may be beneficial longer than previously assumed.

Echoing this, Ms. Piasta emphasized the need to reconsider the timing of hormone therapy, advocating for a proactive approach. “Many clinicians tell women to wait a full year without a period before starting hormone therapy or to delay until symptoms become unbearable, based on outdated fears from the Women’s Health Initiative study,” she said.

However, Dr. Mosconi’s study and others suggest that early therapy, even in perimenopause, and continued long-term treatment may reduce the risk of chronic diseases such as cognitive decline and dementia. “This is a complete paradigm shift from current medical practice regarding hormone therapy,” Ms. Piasta noted.

The researchers plan to use PET imaging to further explore the long-term impacts of changing estrogen levels, including the effects of estrogen therapy on brain health and menopause symptom relief.

“We hope to learn, for example, whether ER density changes with estrogen therapy, and if that leads to fewer symptoms and better performance on cognitive tests,” Dr. Mosconi, who also serves as the director of the Alzheimer’s Prevention Program at Weill Cornell Medicine and NewYork-Presbyterian, said in the statement.

The study could also have implications for neurodegenerative diseases such as dementia and Alzheimer’s. A 2017 study in Frontiers in Aging Neuroscience noted the “neuroprotective effect of estrogen” highlighted by several investigations. The Alzheimer’s Society suggests that the decline in estrogen during menopause may be linked to a higher risk of Alzheimer’s and other dementias.

According to Dr. Mosconi, the new research demonstrates the remarkable plasticity of the human brain, particularly in women. Contrary to the belief that the brain becomes fixed after adolescence, it reveals that women’s brains continue to adapt and change according to their unique needs as they age.