Menopause may unmask vulnerability to Alzheimer’s disease, other dementias
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Key takeaways:
- Menopausal hormone therapy can sustain and promote healthy brain aging, but timing of therapy is key.
- An investigational alternative to estrogen, PhytoSERM, may treat menopausal symptoms.
BOSTON — Menopause is a neurologic transition involving metabolic and immune systems of the brain, and timely estrogen therapy could reduce the risk for developing dementias and other neurogenerative diseases, according to a speaker.
Women may begin to experience menopausal symptoms, such as hot flashes, disrupted sleep and altered cognitive function, during the early midlife phase of chronological aging, Roberta Diaz Brinton, PhD, director of the Center for Innovation in Brain Science and professor of pharmacology and neurology and the University of Arizona, said during a plenary presentation at ENDO 2024. It is during this time that menopausal hormone therapy with estrogen can be beneficial for reducing bothersome menopausal symptoms. Emerging research also suggests that estrogen, which promotes glucose metabolism in the brain, can also reduce risk for dementias such as Alzheimer’s disease, if HT is prescribed at the right time, Brinton said.
“Women who receive menopausal HT for menopausal symptoms at the time of the menopause — not 5, 10 or 20 years later — have a reduced risk for developing all age-associated neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, ALS and other dementias,” Brinton said. “Moreover, the longer a woman was on HT, the greater the reduction or risk. So, why is there such a controversy?”
Despite data suggesting protective benefits of HT, many women fear risk for developing breast cancer, Brinton said.
“If estrogen is beneficial on the brain, why do 80% of women not elect to receive HT for menopausal symptoms?” Brinton said. “One answer: the fear of breast cancer. If we were to intervene to sustain women’s brain health, we had to address their breast health.”
Brinton said the field of breast cancer research has demonstrated the benefits of estrogen receptor-beta targeting. Studies show estrogen receptor-beta inhibits estradiol-stimulated proliferation of breast cancer in vitro, inhibits breast cancer cell proliferation in tumor formation and inhibits breast cancer cell migration and formation.
Brinton and colleagues are currently testing the safety and efficacy of a selective estrogen-beta receptor modulator, PhytoSERM, which can promote estrogenic action in the brain without affecting reproductive tissue, including the breasts and uterus, Brinton said.
“Estrogen receptor-beta can be activated at the part of the brain that regulates ... neural stem cell regeneration, increasing beta-amyloid clearance out of the brain, and, most importantly for us, enhances glucose metabolism and oxidative phosphorylation,” Brinton said.
Researchers are currently testing PhytoSERM in two phase 2 clinical trials with post- and perimenopausal women aged 45 to 60 years.
“We want to really ask, can PhytoSERMs promote glucose metabolism in the brain and prevent generation of beta-amyloid plaques in the brain?” Brinton said.
The second trial will focus on reduction of bothersome hot flashes.
“Midlife endocrinological aging — menopause — is a neurological transition that can unmask vulnerability to age-associated neurogenerative diseases,” Brinton said. “This transition involves both the metabolic and the immune systems of the brain, and for menopausal HT, the stage of menopause matters. Estrogens sustain and promote healthy brain again. It does not reverse disease.”
Reference:
ClinicalTrials.org. PhytoSERM to prevent menopause associated decline in brain metabolism and cognition. https://classic.clinicaltrials.gov/ct2/show/NCT05664477. Accessed June 3, 2024.
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Brinton RD. Endocrine aging in midlife: Lessons from the menopausal transition. Presented at: ENDO annual meeting; June 1-4, 2024; Boston.
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