Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women During Working Memory Tasks

Abstract

One of the effects of a decline in circulating estrogen, in animal studies, is to diminish cognitive function. This trial used functional magnetic resonance imaging to learn whether estrogen replacement therapy influences brain activation patterns. The study group, 46 women with natural or surgical menopause ranging in age from 33 to 61 years, participated in a randomized, double-blind, placebo-controlled, crossover trial. They received either 1.25 mg daily of conjugated equine estrogens or a placebo for 3 weeks and, after a 2-week washout interval, were changed over to the other regimen. Verbal memory tasks were presented during magnetic resonance imaging; the stimuli included both pronounceable nonsense words (for verbal memory) and Tamil letters (for nonverbal memory). During verbal storage, estrogen therapy increased activation in the superior frontal gyrus and the inferior parietal lobule, findings confirmed by region-of-interest analyses. Estrogen also sharpened the asymmetry effect on hemispheric encoding and retrieval. An example is a major increase in activation accompanying retrieval tasks in the right superior frontal gyrus, for both verbal and nonverbal stimuli. The left hemisphere was activated more than the right during encoding, and the right hemisphere was activated more than the left during retrieval. Asymmetry was much more evident during estrogen therapy. Information was retrieved with comparable accuracy in the estrogen and placebo conditions, regardless of stimulus type. This study indicates that functional magnetic resonance imaging should be a useful approach to exploring the effects of estrogen on cognitive function in postmenopausal women. It seems that estrogen influences how the brain is organized for memory in this setting. J Am Med Assoc 1999;281:1197–1202