Distinctive Roles of Estrone and Estradiol in Shaping Verbal Memory Circuitry in Postmenopausal Women

This study examines the association of estradiol, estrone, and follicle stimulating hormone (FSH) with brain activation and hippocampal functional connectivity during a functional magnetic resonance imaging (fMRI) task of verbal learning and memory. These analyses were performed in postmenopausal women in order to identify different roles of hormones in brain regions that support verbal memory ability. We hypothesized that women with increased levels of estradiol and estrone, and lower levels of FSH, would display a pattern of activation and functional connectivity with more hemispheric asymmetry. Specifically, verbal memory encoding would be associated with increased activation and connectivity with regions in the left hemisphere, while verbal memory recognition would be associated with increased activation and functional connectivity with regions in the right hemisphere. Data are from the MsBrain study, a cohort study of midlife women (n=98, mean age 59.2 +/- 4.19 years). The study sample included 97 postmenopausal women (one late perimenopausal), 77 of whom are white, 17 Black, two Asian or Pacific Islander, and two mixed race. Participants completed neuropsychological testing, measures of mental and physical health, and an fMRI task of verbal memory encoding and recognition. Task activation was not significantly related to levels of estradiol, estrone, or FSH. Hippocampal functional connectivity was increased with regions associated with brain networks engaged in attentional and executive processes in those with increased levels of estradiol and estrone, but not with FSH. Findings suggest that estrone and estradiol may have some overlapping and some distinct effects on hippocampal functional connectivity in postmenopausal women.