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HomeNeurologyMore brain changes for post-menopausal than for pre-menopausal women – Bonn study

More brain changes for post-menopausal than for pre-menopausal women – Bonn study

Women who have gone through menopause may have more of a brain biomarker called white matter hyperintensities than premenopausal women or men of the same age, according to a recent German study.

White matter hyperintensities are tiny lesions visible on brain scans that become more common with age or with uncontrolled high blood pressure. These brain biomarkers have been linked in some studies to an increased risk of stroke, Alzheimer's disease and cognitive decline.

“White matter hyperintensities increase as the brain ages, and while having them does not mean that a person will develop dementia or have a stroke, larger amounts may increase a person's risk," said study author Dr Monique Breteler, of the German Centre of Neurodegenerative Diseases (DZNE), in Bonn, Germany, and a member of the American Academy of Neurology.

“Our study examined what role menopause may have on amounts of these brain biomarkers. Our results imply that white matter hyperintensities evolve differently for men and women, where menopause or factors that determine when menopause starts, such as variations in the ageing process, are defining factors.’

The study involved 3,410 people with an average age of 54. Of those, 58% were women, and of the women, 59% were post-menopausal. Also, 35% of all participants had high blood pressure and of those, half had uncontrolled high blood pressure.

All participants had MRI brain scans. Researchers looked at the scans and calculated the amount of white matter hyperintensities for each participant. Average total volume for these brain biomarkers was 0.5 milliliters (ml). Average total brain volume was 1,180ml for men and 1,053ml for women. Average total white matter volume, the area of the brain where white matter hyperintensities can be found, was 490ml for men and 430ml for women.

After adjusting for age and vascular risk factors such as high blood pressure and diabetes, researchers found that post-menopausal women had more of these brain biomarkers when compared to men of similar age. In people 45 and older, post-menopausal women had an average total white matter hyperintensities volume of 0.94ml compared with 0.72ml for men. Researchers also found that the increase in brain biomarkers accelerated with age and at a faster rate in women than in men.

Pre-menopausal women and men of a similar age did not have a difference in the average amount of white matter hyperintensities.

Researchers also found that post-menopausal women had more white matter hyperintensities than pre-menopausal women of similar age. In a group of participants ages 45 to 59, post-menopausal women had an average total volume of white matter hyperintensities of 0.51ml compared to 0.33ml for pre-menopausal women.

There was no difference between post-menopausal and pre-menopausal women using hormone therapy. Breteler said this finding suggested that hormone therapy after menopause may not have a protective effect on the brain.

Unrelated to menopausal status, women with uncontrolled high blood pressure had higher amounts of this brain biomarker than men.

“It has been known that high blood pressure, which affects the small blood vessels in the brain, can lead to an increase in white matter hyperintensities,” said Breteler. “The results of our study not only show more research is needed to investigate how menopause may be related to the vascular health of the brain. They also demonstrate the necessity to account for different health trajectories for men and women, and menopausal status. Our research underscores the importance of sex-specific medicine and more attentive therapy for older women, especially those with vascular risk factors.”

A limitation of the study was that researchers did not know the exact age of menopause onset or whether some participants were peri-menopausal.

The study was published in the online issue of Neurology, the medical journal of the American Academy of Neurology.

Study details
The Relation Between Sex, Menopause, and White Matter Hyperintensities: The Rhineland Study

Valerie Lohner, Gökhan Pehlivan, Gerard Sanroma, Anne Miloschewski, Markus D. Schirmer, Tony Stöcker, Martin Reuter, Monique M. B. Breteler.

Published in Neurology on 22 June 2022


Background and objective
Mounting evidence implies that there are sex differences in white matter hyperintensity (WMH) burden in the elderly. Questions remain regarding possible differences in WMH burden between men and women of younger age, sex-specific age trajectories and effects of (un)controlled hypertension, and the effect of menopause on WMH. Therefore, our aim is to investigate these sex differences and age-dependencies in WMH load across the adult life span, and to examine the effect of menopause.

This cross-sectional analysis was based on participants of the population-based Rhineland Study (30 – 95 years) who underwent brain MRI. We automatically quantified WMH using T1-weighted, T2-weighted and FLAIR images. Menopausal status was self-reported. We examined associations of sex and menopause with WMH load (logit-transformed and z-standardised) using linear regression models, while adjusting for age, age-squared, and vascular risk factors. We checked for an age*sex and (un)controlled hypertension*sex interaction and stratified for menopausal status comparing men with premenopausal women (persons aged ≤ 59 years), men with postmenopausal women (persons aged ≥ 45 years), and pre- with postmenopausal women (age range 45 – 59 years).

Of 3410 participants with a mean age of 54.3 years (SD = 13.7), 1973 (57.9%) were women, of which 1167 (59.1%) were postmenopausal. We found that the increase in WMH load accelerates with age and in a sex-dependent way. Premenopausal women and men of similar age did not differ in WMH burden. WMH burden was higher and accelerated faster in postmenopausal women compared to men of similar age. Additionally, we observed changes related to menopause, in that postmenopausal women had more WMH than premenopausal women of similar age.. Women with uncontrolled hypertension had a higher WMH burden compared to men, which was unrelated to menopausal status.

After menopause, women displayed a higher burden of WMH than contemporary premenopausal women and men, and an accelerated increase in WMH. Sex-specific effects of uncontrolled hypertension on WMH were not related to menopause. Further studies are warranted to investigate menopause-related physiological changes, that may inform on causal mechanisms involved in cerebral small vessel disease progression.


Neurology article – The Relation Between Sex, Menopause, and White Matter Hyperintensities: The Rhineland Study (Open access)


See more from MedicalBrief archives:


HRT should be given earlier as menopause ‘reshapes the brainʼ – Nature Scientific Reports


Early menopause may raise dementia risk later – UK study of 150,000 women


HRT not linked to increased risk of dementia — Largest study yet




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