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

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.