The interaction between menopause and the brain has long been underestimated, but recent research is shedding light on the neurological changes occurring during this phase of life and paving the way for new treatments. “We think of menopause as being driven by changes in the ovary,” said Hadine Joffe, who leads research into women’s health and psychiatry at Harvard Medical School in Boston, Massachusetts. “The notion of the brain at the helm of menopause, that is a different concept.”
Understanding Perimenopause and Brain Health
Menopause, defined as the cessation of menstruation for at least 12 consecutive months, usually occurs between ages 45 and 55. However, the perimenopausal period can last for years and has no clear start. It’s a gradual process marked by erratic hormone fluctuations and a constellation of symptoms. “It’s not a night and day difference, it’s a long, long process,” said Ami Raval, who studies reproduction and neurology at the University of Miami in Florida. “The ovary is slowly sending the signal, ‘hey, it’s time to shut off our physiology.’”
Symptoms during perimenopause, such as hot flashes, irregular periods, anxiety, and cognitive issues, can be significant. Hot flashes also contribute to disrupted sleep, which can in turn impact blood pressure, metabolic changes, and mood.
This transitional phase, and fluctuating estrogen, are believed to affect brain health in later life. Estrogen plays a crucial role in brain function, stimulating glucose uptake and energy production. As estrogen declines, changes in the brain may cause inflammation and increase the risk for women to experience neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease later in life.
Challenges in Menopause Research and Treatment
Perimenopause’s complex nature, with varying durations and symptoms, poses challenges for researchers. Long-term grant programs have been scarce, creating funding uncertainties and discouraging researchers from investigating menopause further. The lack of clarity surrounding hormone replacement therapy (HRT) further complicates treatment options. The Women’s Health Initiative study in 2002 highlighted the potential risks of HRT, leading many women to abandon this therapy. Since then, smaller studies have suggested potential benefits for cardiovascular health and bone preservation when starting HRT during perimenopause.
Non-Hormonal Treatment — A Promising Milestone
In the 1990s, Naomi Rance, a neuropathologist at the University of Arizona in Tucson, discovered that neurons in the hypothalamus doubled in size after menopause. This ignited her interest in learning more about the menopause-brain connection. She later studied temperature changes in rats’ tails as an indication of hot flashes. Her work connecting this common symptom of menopause to the hypothalamus contributed to the development of fezolinetant, the first non-hormonal therapy to be approved by the Food and Drug Administration for hot flashes.
Fezolinetant is a neurokinin 3 (NK3) receptor antagonist that works by binding to and blocking the NK3 receptor, which affects how the brain regulates body temperature. The drug’s approval signals a shift from viewing menopause as a reproductive issue to one with neurological causes and effects. The medication’s development also shows that research into menopausal symptoms is finally gaining recognition and momentum.
The Path Forward
The intersection of menopause and brain health is a compelling and vital area of research that has long been overlooked. With increased interest and funding, research into neurological changes during perimenopause is expanding. A better understanding of these changes and their potential impact on brain health later in life holds promise for improving the quality of life for women during menopause and beyond. As the global number of postmenopausal women is expected to surpass one billion in the next few years, this area of study could have important health implications worldwide.
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