Preliminary evidence that long-term estrogen use reduces white matter loss in aging

Abstract

Despite numerous studies showing neurotrophic and neuroprotective effects of estrogen in animal models, the long-term effects of estrogen use on brain morphology in older women are not known. Thus, we compared ventricular, cerebrospinal fluid, white matter, and grey matter volumes estimated from magnetic resonance images of postmenopausal women with more than 20 years exposure to unopposed estrogen, women who were not on estrogen, and young healthy women. Estrogen users had significantly smaller ventricles and greater white matter volumes than non-users, but hormone exposure did not affect grey matter volumes. Young healthy women had significantly smaller ventricles, less cerebrospinal fluid and more grey matter than both groups of older women. However, they had comparable white matter volumes to older women on estrogen. These findings suggest that long-term estrogen protects against white matter loss in aging. This adds to findings from other studies suggesting estrogen is neuroprotective of the hippocampus and other regions in older women.

Figure 1

Central figure is a representative MRI slice to illustrate ROIs. Ventricles (yellow border), CSF (red border; defined as the strip along the perimeter of the brain from cortical gray matter to the skull as well as sulcal islands of CSF within the parenchyma), white matter (green border, delineated outward from the ventricles until it outlined the contrast border between gray and white matter); and gray matter (calculated as: ICV − CSF + WM + ventricles) volumes were normalized by dividing by intracranial volume (ICV). ICV from each slice included everything inside the innermost edge of the skull (white band). Intra-rater reliability was high (repeated measures p’s> .15 for all regions) as were correlations among repeated measurements for each of the ROI’s (all r’s>.93). Graphs are comparisons of regions of interest among women using estrogen (EW), those not using estrogen (NONE), and young women (YW) (ANOVA). On the graphs, an asterisk denotes significant differences among groups (p<.05). Error bars are standard error of mean. NONE have larger ventricles than both EW and YW. EW have smaller ventricles than NONE but larger ventricles than YW. YW have less CSF than EW and NONE women who do not differ from each other. EW and YW have more white matter than NONE, but did not differ from each other. YW have more gray matter than EW and NONE, who did not differ from each other.