Gray matter differences associated with menopausal hormone therapy in menopausal women: a DARTEL-based VBM study

Menopausal hormone therapy (MHT) in women can reduce troublesome menopause symptoms and prevent cognitive decline. This cross-sectional study investigated the MHT-related effect on brain morphology and its association with sex hormones in menopausal women by using an optimized diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL)-based voxel-based morphometry (VBM) method. Twenty-one menopausal women without MHT (noMHT) and 20 menopausal women with MHT were included in this study. Magnetic resonance imaging data were processed using SPM 12 with DARTEL-based VBM whole brain analysis approach. A 2-sample t-test and analysis of covariance (ANCOVA) adjusting for age and total intracranial volume were used to compare GM volume between noMHT and MHT women. The association between MHT (treatment period, hormones levels) and brain volume variations were analyzed by Spearman correlation. MHT women showed significantly larger volumes of the superior/middle/inferior frontal gyri, hypothalamus, inferior temporal gyrus, parahippocampal gyrus, hippocampus, cerebellar cortex, postcentral gyrus, precuneus, angular gyrus, supplementary motor area, superior occipital gyrus, and precentral gyrus compared to the noMHT women. The volumes of the angular gyrus and hypothalamus in MHT women positively correlated with treatment period. On the other hand, the hypothalamic volume negatively correlated with FSH and LH levels, and the volumes of the inferior frontal gyrus, and angular gyrus negatively correlated with progesterone levels, respectively. MHT-treated women showed larger GM volume than noMHT women. The anatomical structures that showed greater volume in association with MHT included the deep brain areas, frontal, temporal, parietal, and occipital gyri.