Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks

Context Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with m any, but not all, studies showing a positive influence of estrogen on verba l memory in postmenopausal women. Objective To investigate the effects of estrogen on brain activation patter ns in postmenopausal women as they performed verbal and nonverbal working m emory tasks. Design Randomized, double-blind, placebo-controlled, crossover trial from 1 996 through 1998. Setting Community volunteers tested in a hospital setting. Patients Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). intervention Twenty-one-day treatment with conjugated e quine estrogens, 1.25 mg/d, randomly crossed over with identical placebo an d a 14-day washout between treatments. Main Outcome Measures Brain activation patterns measured using functional m agnetic resonance imaging during tasks involving verbal and nonverbal worki ng memory. Results Treatment with estrogen increased activation in the inferior pariet al lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen al so increased activation in the right superior frontal gyrus during retrieva l tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retr ieval asymmetry (HERA) effect. Estrogen did not affect actual performance o f the verbal and nonverbal memory tasks. Conclusions Estrogen in a therapeutic dosage alters brain activation patter ns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.