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Am Fam Physician. 2004;70(8):1575-1576

Estrogen has been shown to have unequivocal positive neuronal effects and to enhance neurotransmitters. However, recent critical reviews have not supported estrogen supplementation for improvement of cognitive performance. Buckwalter and colleagues conducted a study to compare cognitive performance in a population of aging women who were receiving hormone therapy compared with those who were not.

Women were recruited from the Women’s Memory Study. Women who were receiving hormone therapy were randomly selected and matched with women who were not receiving hormone therapy in three age categories (75 to 79 years, 80 to 84 years, and 85 to 89 years). A total of 210 patients were assessed with a battery of tests that focused mainly on memory, which is reported to be most sensitive to estrogen exposure.

Fifty-eight of those receiving hormone therapy and 47 of those not receiving hormone therapy agreed to participate in the study. There were no significant differences between the two groups on any aspects of the California Verbal Learning Test or the Logical Memory subtest, and no differences on any of the neuropsychologic tests. Separate analyses did not change these results. There were no differences when nonusers of hormone therapy were subdivided into past users and never-users of hormone therapy. Nor did it make any differences if users were taking estrogen alone or estrogen plus progestin.

In spite of previous studies that have found a positive effect of estrogen on cognition, this study suggests that hormone therapy does not improve cognitive performance. A possible explanation for the lack of benefit in this study compared with several studies showing positive findings may relate to the aging brain, which may be less responsive to estrogen. The current study’s findings are consistent with a previous randomized trial that showed no benefit of hormone therapy on cognition in very old women.

editor’s note: Recent studies of the cognitive benefits of hormone therapy are not encouraging, although the results of larger, definitive trials are not due until 2010. One Cochrane review of the immediate effects of hormone therapy on cognition in post-menopausal women with dementia showed no benefit.1 Another study showed benefit if hormone therapy had been used for 10 years or longer, but not within 10 years before the onset of Alzheimer’s disease.2 It seems almost certain that short-term hormone therapy use near the onset of dementia or in the treatment of dementia is not effective. Even if long-term preventive benefits are found, they may not be clinically compelling.—c.w.

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