Earlier Menopause, Reduced Cardiac Function Potentially Linked With Negative Impacts on Brain Health

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Earlier menopause and reduced cardiac function may negatively impact brain health, researchers wrote in a study presented at The Menopause Society 2025 Annual Meeting.

These findings, according to the investigators, demonstrate a crucial need for integrating sex-specific factors, such as menopause, into dementia risk research to inform both targeted prevention and therapeutic strategies more accurately.¹

Reduced cardiac function can affect brain health by limiting the supply of oxygen and nutrients, according to a news release from The Menopause Society. These reductions in blood flow can damage brain tissue, contribute to silent strokes, and increase the risk of dementia, emphasizing a critical connection between heart and brain health. Further, earlier age at menopause has been shown to affect brain health negatively, with accumulating data suggesting that earlier menopause is associated with a higher risk of cognitive decline and dementia related to Alzheimer disease later in life.²

Compared with men, women face a higher risk of developing both cardiovascular disease (CVD) and Alzheimer disease dementia. Additionally, CVD is linked to an increased likelihood of Alzheimer disease dementia, particularly among younger women. Menopause, a significant endocrine transition, is characterized by the depletion of ovarian hormones, including estradiol and progesterone. During this transition—especially when it occurs earlier than average—there are increased risks of both CVD and Alzheimer disease dementia. For their study, the authors evaluated whether earlier age at menopause influences the associations between cardiac function and gray matter volume (GMV), white matter hyperintensity (WMH) burden, and cognitive performance.^1,2

The authors analyzed data from postmenopausal female participants enrolled in both the Canadian Alliance for Healthy Hearts and Minds Study and the Ontario Health Study. Cardiac function was assessed using resting left ventricular ejection fraction (LVEF) measured on cardiac MRI. Brain MRI was used to quantify GMV and WMH burden. Patient cognition was assessed with the Montreal Cognitive Assessment (MoCA) and the Digit Symbol Substitution Test (DSST). Linear regression models assessed the interactive associations of age at menopause and LVEF on brain and cognitive outcomes, with adjustments for age, ethnicity, years of education, menopausal hormone therapy, cause of menopause (eg, surgical, spontaneous), visceral adipose tissue, systolic blood pressure, cardiac index, and intracranial volume (for brain outcomes) made if necessary.¹

“We still don’t fully understand how menopause, and especially earlier menopause, affects brain aging. By examining the intersection of heart and brain health, we were keen to shed light on this important but often overlooked area of research,” lead author Tallinn Splinter, from the University of Toronto and Sunnybrook Research Institute, said in a news release.²

In total, 701 participants with a median age of menopause of 51 ± 5.5 years (range: 25–61 years) and a mean LVEF of about 65 ± 6.3% (range: 45%–80%) were enrolled in the study. The investigators observed that age at menopause moderated the associations between LVEF and brain outcomes, with earlier age at menopause strengthening the association between lower LVEF and reduced GMV (β = –86.45; p = .0142) and increased WMH burden (β = .0012, p = .013). Of note, the observed associations between age at menopause and LVEF on cognitive outcomes were not considered significant (MoCA: β = .0024, p = .251; DSST: β = –0.0046, p = .697).¹

These data suggest that earlier menopause and reduced cardiac function may have a compounding negative effect on brain health.¹ Pharmacists play an important role in this area by helping identify and manage cardiovascular and cognitive health risks in postmenopausal women, counseling on preventive therapies and lifestyle modifications, and supporting coordinated care that integrates sex-specific factors into overall health management.

“These findings underscore the importance of integrating sex-specific factors, such as age at menopause, into research on dementia risk and informing targeted prevention and intervention strategies,” Stephanie Faubion, MD, MBA, FACP, medical director for The Menopause Society, said in the news release.²

REFERENCES

1. Splinter T, Alexander MW, Kirkham A, Einstein G, Rabin JS. The Combined Influence of Earlier Menopause and Cardiac Function on Brain Health. Presented at: The Menopause Society Annual Meeting; Orlando, Florida. October 21–25, 2025.

2. The Menopause Society. Earlier Menopause and Reduced Cardiac Function Can Take a Toll on Brain Health. News release. October 17, 2025. Accessed October 24, 2025. https://menopause.org/press-releases/earlier-menopause-and-reduced-cardiac-function-can-take-a-toll-on-brain-health