Verbal memory performance of postmenopausal women on estradiol therapy is positively correlated with regional brain metabolism in receptive language and auditory association areas

Objectives Hormone therapy (HT) users have higher verbal memory performance compared to non-users, while relative effects of conjugated equine estrogen (CEE) vs. 17beta-estradiol (E) remain controversial. This study examined the relationship between verbal memory and regional brain metabolism in women taking CEE vs. E.

Methods Data from the first 53 subjects studied are reported here. All were taking E (35) or CEE (18) at time of recruitment into a prospective randomized study of HT effects on brain. Groups were similar in years of education (17±2, 16±2; av±SD), age at menarche (13±2, 13±2), age at menopause (48±5, 45±8), age at recruitment (57±5, 58±5) and years of HT (9±6, 11±6). All subjects underwent comprehensive neuropsychologic testing including scored assessment of their verbal memory cognitive domain, and brain FDG-PET. Regional cerebral activity was analyzed by statistical parametric mapping methods.

Results Verbal memory performance of E-users was 3 SD higher than that of CEE-users, and correlated most significantly with metabolism in Wernicke’s area (p=0.003) and auditory association cortex (p=0.002). Moreover, metabolism in these two areas was significantly greater (t=4.41, t=4.67; p<0.0005) in E-than CEE-users.

Conclusions Verbal memory was better in women taking E than CEE, and cognitive differences were associated with metabolic differences in receptive language and auditory association areas, consistent with regionally specific neuroprotection by E.