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

Abstract

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 17β-estradiol (17β-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, as part of a larger longitudinal study. Setting-Academic research clinic.Participants-68 healthy postmenopausal women (aged 49-68) receiving either 17β-E or CEE for at least one year and at increased risk for Alzheimer's disease (AD).Measurements-Neuropsychological test battery of the cognitive domains of attention/working memory/processing speed, verbal memory, visual memory, and executive functioning.Results-Women receiving 17β-E showed significantly better verbal memory performance compared to women receiving CEE, regardless of age, IQ, years of education, risk factors for AD (including APOE-ε4 carriership), duration of endogenous and exogenous estrogen exposure, concurrent progesterone use, or natural or surgical menopause status.Conclusions-Verbal memory performance was better in menopausal women receiving 17β-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 that differential effect of the type of HT on verbal memory, with 17β-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.

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

“…Keenan et al (320), for example, found that measures of executive function, but not memory more generally, were improved in a small sample of women taking HT (composition unfortunately not reported). Furthermore type of HT plays a role as verbal memory performance is better in postmenopausal women receiving 17β-estradiol compared to CEE in a sample of women with risk factors for AD (674). Additionally, among postmenopausal women at risk for AD, 17β-estradiol use was associated with a three standard deviation advantage in verbal memory relative to women taking CEE (572).…”

“…HT composition likely impacts cognitive outcome among women with Alzheimer's disease, too. For example, among women with risk factors for Alzheimer's disease, verbal memory performance is better in women taking 17-β estradiol compared to CEE (572,674).…”

Cognitive effects of diphenyl diselenide and estradiol treatments in ovariectomized mice

“…Some studies have reported that 17b-estradiol (E 2 ) administration can attenuate impaired cognitive performance associated with menopause (Sherwin, 2000) and also enhance verbal (Wroolie et al, 2011) and nonverbal (Smith, Giordani, Lajiness-O'Neill, & Zubieta, 2001) memory performance in menopausal women. However, there are several risks associated with the use of current estrogen therapies in humans, mainly the increased incidence of breast and endometrial cancer, heart disease, and stroke (Chen, 2009;Lacey et al, 2002;Miller, Chan, & Nelson, 2002;Stefanick et al, 2006;Wassertheil-Smoller et al, 2003).…”

Update on the effect of estradiol in postmenopause women with Alzheimer’s disease: a systematic review

“…We found that the positive studies administered E2 either intramuscularly or transdermally [11], whereas the RCTs that failed to find a beneficial effect of estrogen on cognition administered CEE orally [1,5,12,13]. This observation raises the possible pharmacologic issue that the efficacy of E2 might be superior to that of CEE [14]. Furthermore, there is reason to believe that E2 easily diffuses into the brain, whereas the ability of estrone sulfate (the major metabolite of CEE) to do so is negligible [15].…”