Abstract
Background: The aging process and declining estradiol levels are two important factors that cause structural brain alterations. Many prior studies have investigated these two elements and revealed controversial results in menopausal women. Here, a cross-sectional study was designed to individually evaluate estradiol-related structural changes in the brain.Methods: A total of 45 early menopausal women and 54 age-matched premenopausal controls were enrolled and subjected to magnetic resonance imaging (MRI) scans, blood biochemistry tests, and neuropsychological tests. MRI structural images were analyzed using FreeSurfer to detect changes in subcortical and cortical volumes as well as cortical thickness. Finally, structural brain data as well as clinical and neuropsychological data were used for Pearson’s correlation analyses to individually determine estradiol-related structural and functional changes in the brains of early menopausal women.Results: Compared with the premenopausal controls, the early menopausal women showed significant subcortical volumetric loss in the left amygdala and right amygdala, higher serum follicle-stimulating hormone (FSH) levels, more recognizable climacteric and depressive symptoms, decreased quality of sleep, and decreased working memory and executive functions. Simultaneously, FSH levels were related to lower working memory accuracy and longer working memory reaction time. Decreased subcortical volume in the bilateral amygdala was also related to lower working memory accuracy and longer executive reaction time in early menopausal women.Conclusion: The data suggest that estradiol deficiency in early menopausal women can lead to subcortical volume and functional brain changes, which may contribute to further understanding the neurobiological role of declined estradiol levels in early menopausal women.
Highlights
With the aging process and a progressive reduction in naturally circulating levels of sex hormones, menopausal women experience a range of menopausal symptoms, including declined cognition and structural alterations in the brain (EnglerChiurazzi et al, 2016; Koothirezhi and Ranganathan, 2021; Peacock and Ketvertis, 2021)
Some studies found that postmenopausal women who received hormone therapy (HT) displayed larger hippocampal volumes and better cognition than those who used placebo (Boccardi et al, 2006; Genazzani et al, 2007; Erickson et al, 2010a)
Other studies demonstrated no differences in hippocampal volume and cognition before and after HT (Eberling et al, 2004; Raz et al, 2004)
Summary
With the aging process and a progressive reduction in naturally circulating levels of sex hormones, menopausal women experience a range of menopausal symptoms, including declined cognition and structural alterations in the brain (EnglerChiurazzi et al, 2016; Koothirezhi and Ranganathan, 2021; Peacock and Ketvertis, 2021). It should be noted that these studies combined the two factors of sex hormone deficiency and age, which worked together to cause the neurotoxicity effects (Jose et al, 2013; Grimm and Eckert, 2017). There have been very few neuroimaging studies that individually evaluated hormonerelated changes in the brain among perimenopausal women. The aging process and declining estradiol levels are two important factors that cause structural brain alterations. A cross-sectional study was designed to individually evaluate estradiol-related structural changes in the brain
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