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.