Abstract / Summary
Abstract Menopause is a critical transitional stage in women’s lives, yet evidence on its impact on brain structure remains inconsistent, and large-sample neuroimaging studies are limited. Here, we applied whole-brain morphometry techniques to evaluate differences between pre- and post-menopausal women in terms of gray matter volume, cortical thickness and cortical gyrification. We processed and analyzed T1-weighted brain scans of 4098 women (1033 pre-menopausal; 3065 post-menopausal) from the UK Biobank. Post-menopausal women exhibited greater gray matter volume than pre-menopausal women primarily in the right temporal lobe, encompassing the amygdala and the hippocampus, and extending to the left temporal lobe and occipital regions. Post-menopausal women also exhibited greater cortical thickness in the frontal lobe and the supramarginal gyrus, whereas no differences in cortical gyrification were observed. These findings were consistent across multiple sensitivity analyses addressing age differences, peri-menopausal status, and other potential confounds. The spatial pattern of differences between post-menopausal and pre-menopausal women considerably overlaps with regions affected early in Alzheimer’s disease, such as the medial temporal lobe and the supramarginal gyrus. Our findings of larger gray matter volume and greater cortical thickness in post-menopausal women may reflect compensatory mechanisms. Speculatively, these findings align with the biphasic model of brain structural changes in Alzheimer’s disease. Further research with longitudinal designs is required to elucidate the exact mechanisms underlying the brain structural differences associated with menopause.