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Hot flashes and night sweats in middle-aged women are associated with greater volume of white matter hyperintensity (WMHV), a marker of small vessel disease in the brain, in new findings that challenge 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,” the said study researcher Rebecca C. Thurston, PhD, Pittsburgh Foundation Chair in Women’s Health and Dementia and professor in the Department of Psychiatry at the University of Pittsburgh, Pittsburgh, Pennsylvania. Medscape Medical News.
The findings were published online on October 12 neurology
An important transition
Previous research shows that these symptoms are associated with worsening cardiovascular health in women.
More than 70% of women suffer from VMS, which are frequent and/or severe in approximately one third of patients.
However, Thurston said, menopause is also increasingly recognized as an important transition for women’s brain health. Specifically, he noted, some studies have linked menopause to an increased risk of stroke, Alzheimer’s disease (AD) and cognitive impairment.
To examine the potential impact of VMS on women’s brain health, 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 (average body mass index [BMI]26.74) and normotensive.
All participants underwent 3 days of follow-up. On the first day they wore a VMS monitor that collected physiological data. Throughout the follow-up period, they maintained an electronic VMS diary and wore a wrist actigraphy unit and kept a sleep diary.
For both physiological and self-reported VMS, the researchers analyzed total rates over a 24-hour period and separately during wakefulness and sleep.
On average, study participants had five physiologically detected VMS during a 24-hour period. These included three hot flashes while awake and two night sweats during sleep. Night sweats, Thurston said, are physiologically the same as hot flashes, but they only occur at night.
The researchers also assessed glucose, insulin and lipids. Participants underwent magnetic resonance imaging to measure WMHV in the whole brain and in six brain regions, including the periventricular, deep, frontal, temporal, parietal, and occipital lobes.
“WMHs are of heterogeneous origin and it has been postulated that their location may be relevant to their etiology and clinical implications,” the researchers note.
The researchers adjusted for age, race, education, BMI, smoking, systolic blood pressure, antihypertensive medications, homeostatic model assessment, high-density lipoprotein cholesterol, and triglycerides.
Adjusted analysis revealed that more frequent physiological VMS were associated with greater whole-brain WMHV.
Robust, replicable
“This was really robust and highly replicable, you could adjust anything you wanted in the model and you could still see that association,” Thurston said.
It’s not clear why the associations were stronger for sleep VMS and less so for waking VMS
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, VMSs 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 that we think the frontal lobe is particularly sensitive to cardiovascular disease risk factors,” Thurston said. “It coalesces around the idea that there is this vascular component to these vasomotor symptoms.”
The study showed no associations for self-reported VMS. “I think the problem with physiological versus self-report is a measurement problem,” Thurston said. “Keep in mind that it’s very difficult to accurately self-report how many gasps you have during sleep because you’re asleep.”
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 researchers note.
To manage hot flashes, patients “have to do the normal things,” such as quitting smoking and treating high blood pressure and diabetes, Thurston said.
Also, if hot flashes are causally related to WMHV, it would be important to treat them. Some research suggests that treating hot flashes improves memory, “but we don’t know if that’s true for WMHV,” Thurston said.
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, Thurston said.
However, many 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 potentially ineffective treatments being marketed to women,” Thurston said. “So it’s incredibly important for women to shopper beware.”
A great first step
Commenting on this new research, Elaine Jones, MD, a teleneurologist based in Sarasota, Florida, and a member of the American Academy of Neurology, said Medscape Medical News found the study interesting and noteworthy.
That vasomotor symptoms seem to have an impact not only on cardiovascular health but also on cerebrovascular health “makes sense; where the heart goes, the brain follows,” Jones said.
“We pay a lot of attention to cardiovascular issues in women, and I think we’re very behind on the cerebrovascular aspects.”
But Jones is concerned about the confusion and that “a real correlation has yet to be shown” between VMS and WMHV.
“With these studies, there are a lot of variables that aren’t necessarily controlled for, and I think that just needs to be figured out more,” he said. But this new study “is a great first step.”
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