Effects of Conjugated Equine Estrogens on Cognition and Affect in Postmenopausal Women with Prior Hysterectomy

Context: Different menopausal hormone therapies may have varied effects on specific cognitive functions. We previously reported that conjugated equine estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women. Objective: The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy. Design: This was a randomized, double blind, placebo-controlled clinical trial. Setting: The study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers. Participants: Participants were 886 postmenopausal women with prior hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr. Intervention: Intervention was 0.625 mg of CEE daily or placebo. Main Outcome Measures: Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured. Results: Compared with placebo, unopposed CEE was associated with lower spatial rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr of continued treatment. CEE did not significantly influence change in other cognitive functions and affect. Conclusions: CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy. CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment. Overall, CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women. (J Clin Endocrinol Metab 94: 4152-4161, 2009)