Effects of estrogen therapy on age-related differences in gray matter concentration

Objective Previous studies suggest that estrogen therapy (ET) either improves or has a neutral effect on the structural integrity of neural tissue in postmenopausal women. The inconsistency in the findings of previous studies is likely to be due to a variety of methodological factors. In this study, we attempted to overcome many of these factors. Method We used magnetic resonance imaging and voxel-based morphometry to study the long-term effects of ET commenced immediately postmenopause on age-related differences in (1) normalized lobar brain volumes and (2) regional gray and white matter concentrations. We included 61 healthy women: 23 young, 19 postmenopausal long-term ET users (who had started ET around the time of menopause) and 19 postmenopausal ET never-users. Results We report that ET users did not differ significantly from never-users in age, duration of menopause, general intelligence, mnemonic function or apolipoprotein E allele frequency. Compared to young women, both ET users and never-users had significantly smaller normalized volumes of whole brain and left and right frontal lobes, but ET users did not differ significantly from never-users in bulk brain volumes. Compared to young women and ET users, never-users had significantly lower gray matter concentration bilaterally in orbitofrontal cortices and cerebellum, right inferior frontal and precentral cortices, and left paracentral cortex. Conclusion These findings suggest that initiation of ET around the time of menopause may modulate age-related differences in regional gray matter concentration. The functional significance of our findings remains unknown.