Women with multiple sclerosis (MS) show accelerated loss of gray matter, hippocampal, and anterior cingulate volume after menopause, according to study results presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress 2025, held in Barcelona, Spain from September 24 to 26, 2025.
Reproductive aging may influence the risk for cognitive impairment and age-related atrophy. Prior research in MS has connected the postmenopausal transition to neurodegeneration and whole-brain gray matter loss, but longitudinal, substructure-specific changes have been less well characterized.
In a prospective longitudinal study, researchers evaluated 1282 annual brain MRI scans from 179 cisgender women with MS collected before and after menopause. They segmented MS lesions and brain regions associated with neurodegeneration in MS, including global gray matter, corpus callosum, and thalamus, as well as regions linked to cognition and menopause, including the hippocampus, dorsolateral prefrontal cortex, amygdala, and anterior cingulate.
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This study underscores the menopausal transition as a meaningful window to assess hormonally related changes to brain structures and their relationship to cognition post-menopause.
Outcomes were log-transformed and modeled with linear mixed effects, adjusting for age, MS duration, therapy use, body mass index, smoking, and systemic hormone replacement therapy. The analysis focused on changes in slope at menopause.
The median age at spontaneous menopause was 51 (IQR, 5) years, and 23% of participants used hormone replacement therapy.
After menopause, the rate of volume loss accelerated for global gray matter (95% CI, 0.0001–0.004; P =.022), the left hippocampus (95% CI, 0.0001–0.0005; P =.016), and the left anterior cingulate in both caudal (95% CI, 0.003–0.022; P =.007) and rostral (95% CI, 0.001–0.008; P =.01) divisions.
Conversely, a decelerating rate of change was observed in the mid-posterior corpus callosum (95% CI, −0.016 to −0.003; P =.006). No other evaluated structures showed statistically significant slope changes.
“This may reflect increased vulnerability to hormonal changes in these structures, given the non-significant or opposing associations in structures typically affected by MS, such as the thalamus and corpus callosum,” noted the authors. “This study underscores the menopausal transition as a meaningful window to assess hormonally related changes to brain structures and their relationship to cognition post-menopause.”
This article originally appeared on Neurology Advisor
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