Differences in Verbal Memory Performance in Postmenopausal Women Receiving Hormone Therapy: 17β-Estradiol Versus Conjugated Equine Estrogens

Objective: Much controversy exists and many questions remain unanswered about the effects of hormone therapy (HT) on cognition in postmenopausal women. There is growing evidence suggesting that HT compounds containing conjugated equine estrogen (CEE) have negative effects on cognition whereas 17 beta-estradiol (17 beta-E) either has positive or neutral effects. The present study sought to further examine this issue in a sample of postmenopausal women with risk factors for Alzheimer's disease (AD). Design: Cross-sectional neuropsychological evaluation. Setting: Academic research clinic. Participants: 68 healthy postmenopausal women (aged 49-68) receiving either 17 beta-E or CEE for at least one year with increased risk for AD. Measurements: Neuropsychological test battery of the cognitive domains of attention/working memory/processing speed, verbal memory, visual memory, and executive functioning. Results: Multivariate analyses of variance (MANOVA) showed significantly better verbal memory performance in women receiving 17 beta-E compared to women receiving CEE regardless of age, IQ, years of education, risk factors for AD (including APOE-epsilon 4 carriership), duration of endogenous and exogenous estrogen exposure, concurrent progesterone use, or natural versus surgical menopause status. Conclusions: Verbal memory performance was better in postmenopausal women receiving 17 beta-E compared to CEE in a sample population of women with risk factors for AD. Genetic risk for AD as well as other confounds did not affect this finding. The results suggest a differential effect of HT type on verbal memory, with 17 beta-E being a preferential compound. Further evaluation of HT types, regimens and duration of use on cognitive performance in postmenopausal women in a controlled longitudinal design is warranted. (Am J Geriatr Psychiatry 2011; 19:792-802)