It is well known that approximately two-thirds of all people living with Alzheimer’s disease in the U.S. are women. The prevailing thought is that women live on average, four and a half years longer than men. However, research shows that a strong contributing factor is that the disease can start earlier in women during the menopausal transition.

The link between menopause and Alzheimer’s disease

“Hot flashes are actually a sign of something occurring in the brain,” explains Roberta Diaz Brinton, Ph.D., Director, Center for Innovation in Brain Science and Regents Professor of Pharmacology and Neurology at the University of Arizona – College of Medicine – Tucson. “The loss of estrogen during menopause is enough to shift the brain’s glucose metabolism by 20-25% which activates a starvation response in the brain, causing it to look for supplementary fuel. The brain can use its own white matter as fuel, leading to abnormalities and the potential development of Alzheimer’s disease.”

It’s important for women to treat menopausal symptoms, such as hot flashes, cognitive issues or depression, while they are happening not only to avoid discomfort but also to prevent the starvation response in the brain. Hormone replacement therapy is one of the treatment options currently available.

“When menopausal women are given the right dose with the right formulation at the right time, the results for hormone replacement therapy are positive,” says Dr. Brinton. “While controversies with this treatment approach have been widely publicized, most of the findings are based on hormone therapies used many years ago before lower doses and multiple routes of administration, like transdermal, were developed. The link to breast cancer was likely caused by formulations used at the time.”

Testing a new approach to treating menopause symptoms

Up to 80% of women are electing not to receive menopausal hormone therapy because of the perceived risk of breast cancer. Instead, they often suffer through menopausal symptoms or turn to untested over-the-counter products.

After decades of research spanning discovery to translational to clinical trials, Dr. Brinton is leading two phase 2 clinical trials to determine the effect of PhytoSERM on menopausal symptoms, which is a scientifically designed combination of natural plant-based estrogens.

“PhytoSERM selectively targets a type of estrogen receptor, termed estrogen receptor beta, which in the brain promotes the beneficial effects of estrogen effect while simultaneously inhibiting estrogen action in the breast,” explains Dr. Brinton. “This is the perfect combination of promoting brain health while also sustaining breast health.”

The first of the current clinical trials, slated to be completed in the fall of 2025, is designed to determine whether PhytoSERM reduces hot flashes because women often seek products to reduce the frequency and severity of them. The second trial, which will be completed in 2026, aims to determine whether PhytoSERM sustains glucose metabolism in brain to reduce the risk of Alzheimer’s disease. Once completed, Dr. Brinton and her team will publish the results, paving the way to make PhytoSERM available as an over-the-counter option.

What’s next for PhytoSERM

“PhytoSERM, which is a nutraceutical, is being developed with the same rigor and quality as a pharmaceutical because our goal is to provide women with an over-the-counter product that is both safe and effective,” says Dr. Brinton. “At the end of these two current trials, we’ll have more safety data than any other over-the-counter product available. We’ll also have efficacy data, as well as specific dosing information.”

If PhytoSERM continues to show positive results, it could be available within the next few years, giving women a new option to sustain their brain health while protecting breast health during menopause.

“We’re planning to work through the commercialization strategy over the next year, so once we have the clinical outcomes, and if they are positive, we can advance quickly to provide a safe and effective alternative for menopausal symptoms,” shares Dr. Brinton. “Because our ultimate goal is to prevent Alzheimer’s disease in those at greatest risk, women, we are committed to making PhytoSERM readily available to women across the economic spectrum.”