White matter hyperintensity tied to menopause
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Postmenopausal women had a greater burden of white matter hyperintensity — or WMH — compared with men and premenopausal women, as well as a faster increase in WMH, according to a cross-sectional analysis of the Rhineland Study.
“Our results imply that WMH,” which is associated with neurological conditions such as stroke and cognitive dysfunction, “evolves differently for men and women, where menopause is a defining factor,” Valerie Lohner, MSc, who was a PhD student at the German Center for Neurodegenerative Diseases in Bonn, Germany, at the time of the study, and colleagues wrote.
Lohner and colleagues evaluated WMH in 3,410 participants (mean age, 54.3 years) of the population-based Rhineland Study who underwent brain MRIs. The researchers assessed whether WMH load differs based on sex across the adult life span, and what effect menopause, age and hypertension have on those differences. They compared the findings of premenopausal women and men aged 59 years or younger; postmenopausal women and men aged 45 years or older; and pre- and postmenopausal women aged 45 to 59 years.
More than half (n = 1,973; 57.9%) of the participants were women, 1,167 (59.1%) of whom were postmenopausal. Hypertension was prevalent in 1,208 (35.4%) participants and was uncontrolled in 660 participants.
WMH volume, load
Overall, the median WMH volume was 0.5 mL (interquartile range [IQR], 0.2 mL-1.2 mL), and the median load was 0.1% (IQR, 0.1%-0.3%).
Compared with men aged 59 years or younger, premenopausal women did not have significant differences in WMH load, with a linear load increase with age.
Stratified analyses revealed that postmenopausal women had a higher WMH load compared with men aged 45 years or older, and that the burden accelerated more quickly with age in these women.
Additionally, postmenopausal women aged 45 to 59 years had a higher WMH burden compared with premenopausal women within the same age range. However, both groups experienced a linear increase in WMH burden with age.
Hypertension, WMH
Having hypertension was associated more WMH vs. having no hypertension, and was greater in women compared with men, according to the study. Specifically, uncontrolled hypertension was associated with more WMH in women compared with men and was not related to menopause.
The researchers also found that hormone therapy had no impact on WMH load in postmenopausal women, “suggesting that [hormone therapy] after menopause does not continue this protective effect on the brain.”
“Our results demonstrate the necessity to account for different trajectories for men and women, and menopausal status,” Lohner and colleagues wrote. “This further underscores the importance of sex-specific medicine, and the requirement for a more attentive therapy for older/postmenopausal women, especially with advanced vascular risk factors.”
Perspective
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In this article from the German Center of Neurodegenerative Diseases, Lohner and colleagues reported that white matter intensities — which are brain abnormalities associated with strokes and cognitive impairments — were more common in postmenopausal women than in age-matched men. They also noted that progression of these abnormalities accelerated faster in the postmenopausal women than in men.
The role of estrogen in cognitive decline has been discussed and has been controversial for many years. Indeed, several studies have been undertaken to evaluate whether the administration of estrogen can help prevent some of these changes, with very mixed results in the literature. One controversial explanation that has been proffered is that the higher burden of dementia in women is because men have ongoing estrogen production (in the form of aromatization of androgens to estrogens), whereas postmenopausal women have minimal levels.
As we are approaching the 20th anniversary of the preliminary release of the Women’s Health Initiative data this month, we still need more investigation on these neurological issues and their correlation with vascular changes in older women and the relevance of the timing hypothesis on estrogenic effects in menopause.
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