Common Menopausal Symptoms Tied to Impaired Brain Health

Pauline Anderson

October 27, 2022

Hot flashes and night sweats in middle-aged women are associated with greater white matter hyperintensity volume (WMHV), a marker of small vessel disease in the brain, in new findings that call into question the idea that these symptoms are benign.

These new findings challenge the long-held belief that the most common menopausal vasomotor symptoms (VMS) are benign and of limited clinical significance and "underscore the importance of these vasomotor symptoms for women's brain health," study investigator Rebecca C. Thurston, PhD, Pittsburgh Foundation chair in women's health and dementia and professor, Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, told Medscape Medical News.

The findings were published online October 12 in Neurology.

An Important Transition

More than 70% of women experience VMS, which are frequent and/or severe in about one-third of sufferers. Previous research shows such symptoms are associated with worsening of women's cardiovascular health.

However, said Thurston, menopause is also increasingly recognized as an important transition for women's brain health. Specifically, she noted, some studies have linked menopause to an increased risk of stroke, Alzheimer's disease (AD), and cognitive decline.

To examine the potential impact of VMS on women's brain health, the researchers examined the potential link between these symptoms and WMHV in 226 postmenopausal women. Participants had a mean age of 59 years and were not using hormone therapy. On average, most participants were overweight (median body mass index [BMI], 26.74) and normotensive.

All participants underwent 3 days of monitoring. On the first day, they wore a VMS monitor that collected physiological data. For the entire monitoring period, they kept an electronic VMS diary and wore a wrist actigraphy unit and kept a sleep diary.

For both physiological and self-reported VMS, researchers looked at total rates for a 24-hour period, and separately during wake and sleep.

On average study participants had five physiologically detected VMS over a 24-hour period. These included three hot flashes while awake and two night sweats during sleep. Night sweats, said Thurston, are physiologically the same as hot flashes but just occur nocturnally.

Investigators also assessed glucose, insulin, and lipids. Participants underwent magnetic resonance imaging to measure whole brain WMHV and in six brain regions including periventricular, deep, frontal, temporal, parietal and occipital lobes.

"WMHs are heterogeneous in origin, and it has been postulated that their location may be relevant to their etiology and clinical implications," the investigators note.

Researchers adjusted for age, race, education, BMI, smoking, systolic blood pressure, antihypertension medication, homeostatic model assessment, high density lipoprotein cholesterol, and triglycerides.

Adjusted analysis revealed more frequent physiologic VMS were associated with greater whole brain WMHV. Associations were most pronounced for sleep VMS (sleep VMS: B, 0.173 [P = .004]; 24-hour VMS: B, 0.095, [P = .032]; wake VMS: B, 0.078 [P = .089]).

Robust, Replicable

"This really was robust and highly replicable, you could adjust for anything you wanted in the model, and you could still see this association," said Thurston.

It's not clear why associations were stronger for sleep VMS and less so for wake VMS, she said.

The researchers also found that physiologically detected VMS, particularly sleep VMS, were associated with both greater deep WMHV and greater periventricular WMHV. When considering specific brain regions, VMS were most consistently associated with frontal lobe WMHV. The frontal lobe is responsible for voluntary movement, expressive language, and the ability to plan and organize.

"The reason this is important is we think the frontal lobe is particularly sensitive to cardiovascular disease risk factors," said Thurston. "It coalesces around the idea there's this vascular component to these vasomotor symptoms."

The study did not show associations for self-reported VMS. "I think the issue with physiological versus self-report is a measurement issue," said Thurston. "Keep in mind it's very hard to accurately self-report how many hot flashes you're having during sleep because you're sleeping."

The study is the most definitive to date linking VMS to WMHV, with a large sample size, state-of-the-art assessments of VMS, and rigorous assessment of covariates and potential mechanisms, the investigators note.

To manage hot flashes patients "should do the normal things" like quit smoking and treat high blood pressure and diabetes, said Thurston.

In addition, if hot flashes have a causal relationship with WMHV then treating them would be important. Some research suggests treating hot flashes improves memory, "but we don't know if that's true for WMHV," said Thurston.

There are currently two US Food and Drug Administration (FDA) treatments for VMS — hormone therapy and paroxetine. A new class of agents — neurokinin 3 (NK3) receptor antagonists — is currently being evaluated, said Thurston.

However, numerous other therapies are being marketed to women with little or no science behind them. "The menopause space is the Wild West when it comes to potential nonefficacious treatments that are being marketed to women," said Thurston. "So, it's incredibly important for women to be buyer beware."

"A Great First Step"

Commenting on this new research, Elaine Jones, MD, a teleneurologist based in Sarasota, Florida, and a fellow of the American Academy of Neurology, told Medscape Medical News she found the study interesting and noteworthy.

That vasomotor symptoms appear to have an impact not only on cardiovascular health but also on cerebrovascular health "makes sense; where the heart goes, the brain follows," said Jones.

"We pay so much attention to cardiovascular issues in women and I think we're way behind in terms of cerebrovascular aspects."

But Jones is concerned about confounding and that "a true correlation" between VMS and WMHV "hasn't yet been proven."

"With these studies, there are a lot of variables that are not necessarily controlled for, and I think it just needs to be teased out more," she said. But this new study "is a great first step."

The study was funded by the National Institutes of Health; National Institute on Aging; National Heart, Lung, and Blood Institute; and the University of Pittsburgh. Thurston is a consultant for Astellas, Bayer, Happify Health, Hello Therapeutics, and Vira Health. Jones has disclosed no relevant financial relationships.

Neurology. Published online October 12, 2022. Abstract

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