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

Abstract

Context: Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory. Objective: The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women. Design: This study was a randomized, double-blind, placebo-controlled clinical trial. Setting: Participants were women from 14 of 40 clinical centers of the Women’s Health Initiative (WHI). Participants: Postmenopausal women (1416) 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, were studied. Intervention: Intervention was conjugated equine estrogen (CEE; 0.625 mg) 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, were measured. 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.