Clinical study
Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study

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Abstract

Purpose

To determine if hormone therapy results in better cognitive function in older postmenopausal women.

Subjects and methods

The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized, placebo-controlled trial involving 2763 women with coronary disease. Women were assigned randomly to conjugated estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) in one tablet daily or identical placebo; they were followed for a mean (± SD) of 4.2 ± 0.4 years. Participants at 10 of the 20 HERS centers were invited to enroll in the cognitive function substudy. At the end of the trial, we measured cognitive function in 517 women in the hormone group and 546 in the placebo group using six standard tests: the modified Mini-Mental Status Examination, Verbal Fluency, Boston Naming, Word List Memory, Word List Recall, and Trails B. Cognitive function was not measured at baseline.

Results

The mean age of participants at the time of cognitive function testing was 71 ± 6 years. There were no differences in age-adjusted cognitive function test scores between the two treatment groups, except that women assigned to hormones scored worse on the Verbal Fluency test than women assigned to placebo (15.9 ± 4.8 vs. 16.6 ± 4.8, P = 0.02). Adjustment for other potential confounders and restriction of the analyses to women who had been adherent to study medication did not change the results.

Conclusion

Among older postmenopausal women with coronary disease, 4 years of treatment with postmenopausal hormone therapy did not result in better cognitive function as measured on six standardized tests. Whether these results also apply to elderly women without coronary disease cannot be determined from this study.

Section snippets

Subjects and methods

The design, methods, baseline findings, and main outcomes of the trial have been published 9, 10. Briefly, participants were postmenopausal women younger than 80 years old with established coronary disease and an intact uterus. Participants were assigned randomly to daily oral conjugated estrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) in one tablet (Prempro, Wyeth-Ayerst, Radnor, Pennsylvania) or identical placebo. Randomization was stratified by clinical center. Participants,

Results

Between January 1993 and September 1994, the 10 HERS centers that participated in this ancillary study enrolled 1328 women; 662 were assigned randomly to estrogen plus progestin therapy and 666 to placebo. All participants were fluent in English. By the end of the trial, 61 women in the hormone group and 58 women in the placebo group had died. Twenty-eight women in the hormone group and 22 in the placebo group were willing but unable to complete cognitive testing because of physical problems

Discussion

Compared with placebo, 4 years of treatment with oral estrogen plus progestin did not result in better cognitive function in elderly women. Rather, the age-adjusted mean score on one of the six cognitive tests was statistically significantly worse among women assigned to hormones compared with those assigned to placebo. However, the absolute difference in scores between the groups was small and not likely to be clinically important. Similar proportions of the hormone and placebo groups were

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    This research was funded by Wyeth-Ayerst Research, Radnor, Pennsylvania. Dr. Yaffe is supported by grant K23-AG00888 from the National Institute on Aging and a Paul Beeson Faculty Scholars Award.

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