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A study led by researchers at Weill Cornell Medicine has unveiled significant advancements in understanding the neurobiological changes associated with menopause through positron emission tomography (PET) imaging.

The study employed PET scans with a specialized tracer targeting estrogen receptors (ERs) to analyze brain activity in 54 healthy women aged 40-65. This pioneering approach marks the first use of ER-PET imaging to examine estrogen's impact on the brain in healthy women, providing new insights into cognitive and behavioral effects mediated by estradiol, the most potent form of estrogen.

The findings reveal a progressive increase in ER density across several estrogen-sensitive brain networks among women in perimenopausal and postmenopausal stages compared to premenopausal controls. This phenomenon is interpreted as a compensatory response to declining estrogen levels, wherein brain cells enhance ER expression to maximize estrogen uptake. Weill Cornell Medicine noted that the elevated ER density in these regions correlates not only with menopausal status but also with reported cognitive and mood symptoms related to menopause.

Lead author Dr. Lisa Mosconi, associate professor of neuroscience in neurology and radiology at Weill Cornell Medicine, and director of the Women's Brain Initiative, pointed out the study's significance: "Using this method, we were able for the first time to measure ER activity in the brain and identify potential predictors of common menopause-related symptoms."

Menopause, characterized by decreased estrogen production, triggers various physiological changes including cognitive challenges like "brain fog," and emotional issues such as depression and anxiety. To elucidate the molecular mechanisms underlying these symptoms, a minimally invasive tool for assessing estrogen activity in the brain is essential. The study demonstrates that PET imaging with the ER-binding tracer 18F-fluoroestradiol (FES) fulfills this need effectively.

Published in Scientific Reports on June 20, the research identified distinctive patterns of ER density in key brain regions like the hippocampus, frontal cortex, and thalamus, correlating with cognitive performance and mood outcomes in postmenopausal women. Notably, higher ER densities in cognitive regions were associated with poorer cognitive test scores, while increased densities in mood-related areas corresponded with higher incidences of depression.

The researchers aim to utilize ER-PET imaging to investigate the long-term implications of estrogen level changes in the brain, including sustained low levels post-menopause and increased levels with estrogen therapy.

"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," said Dr. Mosconi, also the director of the Alzheimer's Prevention Program at Weill Cornell Medicine and NewYork-Presbyterian.

Furthermore, the discovery that estrogen receptors (ERs) persist in the brain for up to a decade after menopause, rather than diminishing rapidly, suggests a prolonged "window of opportunity" for estrogen therapy. Elevated ER density observed during perimenopause further supports this notion.