Effects of hormone therapy on brain morphology of healthy postmenopausal women

In Brief Objective: Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume in vivo. Design: Forty healthy postmenopausal women underwent three-dimensional high-resolution magnetic resonance imaging: 17 were never treated, 16 were currently receiving ET, and 7 had had ET in the past. Voxel-based morphometry (VBM) with SPM2 was used, according to an optimized protocol, to compare women under past and current ET to those never treated. Significance threshold was set at P = 0.01, corrected by false discovery rate. Results: Voxel-based morphometry indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum (cluster size, Z coordinates: 5,527; 5.15; −14 −54 −10), the amygdaloid-hippocampal complex (left: 19; 3.55; −22 −4 −18; right: 45; 3.61; 16 −6 −16), and extended to the frontal, temporal, parietal, and occipital neocortex. The comparison current ET versus past ET use showed that women who underwent treatment in the past had greater volumes of gray matter compared to women under current treatment. Conclusions: ET might slow down age-related gray matter loss in postmenopausal women. The structures that exhibited greater volume in association with ET included the cerebellar and cerebral cortices and, typically involved in Alzheimer's disease, the medial temporal structures and the temporoparietal junction. Voxel-based comparison of the gray matter of 40 magnetic resonance images from women treated and not treated with estrogen therapy (ET) showed that treated women have larger brain volumes in the cerebellum, cerebral cortex, and middle temporal structures, and women treated in the past displayed larger volumes than those currently on ET. These findings add to the few and controversial neuroimaging studies on the effects of ET on the brain and suggest a possible protective role of ET in dementia.