Effect of sex and estrogen therapy on the aging brain: a voxel-based morphometry study

Objective: It is still a matter of debate whether estrogen can have a protective effect on brain integrity and against age- and Alzheimer-related assaults. Evidence points toward selective sparing of gray matter (GM) in postmenopausal women using hormone therapy. In the current study, the effect of sex and estrogen therapy (ET) exposure on GM density using voxel-based morphometry was assessed. Methods: High-resolution structural magnetic resonance imaging scans of 46 healthy participants were analyzed using voxel-based morphometry. A total of 15 men and 31 healthy postmenopausal women were included: 15 ET-naive women (never users) and 16 current ET users with an average duration of use of 11 years. Results: Sex differences were found in fronto-temporo-parietal areas, with postmenopausal women having greater GM concentration in the medial prefrontal cortex, temporal cortices, angular gyrus, and precuneus, whereas the men had greater GM density in the superior frontal, inferior temporal gyri, and inferior parietal lobules. ET users compared with never users had greater GM density in the superior frontal gyrus and less GM density in the posterior part of the hippocampus and parahippocampal gyrus, posterior cingulate, and angular gyri. In the group of ET users, a negative association was found between duration of ET use and posterior hippocampus and parahippocampal GM density, whereas a positive association was found in the hypothalamus, striatum, precunei, and inferior parietal lobules. Conclusions: These results point toward a potential regional-and duration-dependent estrogen exposure effect on cerebral areas known to be involved in age-related cognitive functions and Alzheimer and Parkinson diseases.