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This version published online on March 7, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2097
A more recent version of this article appeared on May 1, 2006
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*Compound via MeSH
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*ESTROGENIC SUBSTANCES, CONJUGATED

Submitted on September 20, 2005
Accepted on February 24, 2006

Effects of Combination Estrogen Plus Progestin Hormone Treatment on Cognition and Affect

Susan M. Resnick PhD*, Pauline M. Maki PhD, Stephen R. Rapp PhD, Mark A. Espeland PhD, Robert Brunner PhD, Laura H. Coker PhD, Iris A. Granek MD, Patricia Hogan MS, Judith K. Ockene PhD, Sally A. Shumaker PhD, and for the WHISCA Investigators

National Institute on Aging, Baltimore, MD; Wake Forest University Health Sciences, Winston-Salem, NC; University of Nevada School of Medicine, Reno, NV; State University of New York, Stony Brook, NY; University of Massachusetts Medical School, Worcester, MA

* To whom correspondence should be addressed. E-mail: Susan.Resnick{at}nih.gov.

Context: Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory.

Objective: To determine whether hormone therapy influences changes in specific cognitive functions and affect in older women.

Design: A randomized, double blind, placebo-controlled clinical trial.

Setting: Women from 14 of 40 clinical centers comprising the Women's Health Initiative (WHI)

Participants: 1416 postmenopausal women aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr.

Intervention: 0.625 mg of conjugated equine estrogen (CEE) with 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet (CEE+MPA) or placebo.

Main Outcome Measures: Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization.

Results: CEE+MPA had a negative impact on verbal memory (P ≤ 0.01) and a trend to a positive impact on figural memory (P = 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long-term therapy. CEE+MPA did not significantly influence positive affect, negative affect, or depressive symptoms.

Conclusions: The effect of CEE+MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research.
Key words: Estrogen • Hormone Therapy • Cognition • Memory • Mood • Affect




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