Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD

Abstract

SummaryDifferential cerebral metabolic effects of various hormone therapy formulations, and their associations with cognitive status, remain to be established. The principal aim of the current study wasto assess relationships between regional cerebral metabolism and estrogen-based hormone therapies. Postmenopausal women (n=53) at elevated risk for Alzheimer's disease (AD) were on estrogen-containing hormone therapy for at least one year prior to enrollment in a prospective, randomized clinical trial. Subjects underwent an FDG-PET scan, along with neuropsychological, medical, and demographic assessments at time of enrollment, to be repeated one year following randomization to hormone therapy continuation versus discontinuation, and results from analyses of the baseline assessments are reported here. Across all subjects, years of endogenous estrogen exposure correlated most closely with metabolism in right superior frontal gyrus (p<0.0005). Women taking 17β-estradiol (E) performed 3 standard deviations higher in verbal memory than women taking conjugated equine estrogen (CEE), and their verbal memory performance positively correlated with metabolism in Wernicke's (p=0.003) and auditory association (p=0.002) areas. Women taking progesterone-plus-estrogen had lower metabolism than women taking unopposed estrogen within the mesial and inferior lateral temporal regions (p<0.0005) and the inferior frontal cortex, contralateral to Broca's area (p<0.0005). In conclusion, particular areas of relatively preserved metabolism were seen in women with more years of endogenous estrogen exposure, as well as in women taking estradiol-based formulations or estrogen therapies unopposed by progesterone, together suggesting regionally specific neuroprotective estrogenic effects.

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

“…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). Thus, prefrontal cortex-mediated behaviors, inducing verbal memory are positively affected by HT dependent on type of HT, time since menopause and brain health status at the time of HT use.…”

“…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).…”

Distinct cognitive effects of estrogen and progesterone in menopausal women

“…While cognitive outcomes have been variable across studies of postmenopausal hormone use, in general there have been more positive cognitive effects associated with unopposed estrogen than with combined estrogen/progestin regimens, with progestin appearing to mitigate estrogenic effects in some cases(Rice et al, 2000; Sherwin and Grigorova, 2011; Silverman et al, 2011). This is particularly true for the verbal cognitive domain, which appears to be more influenced by hormone treatment than visual cognition(Carlson and Sherwin, 1999; Jacobs et al, 1998; Krug et al, 2003; Maki, 2005; Resnick et al, 2006; Shaywitz et al, 2003; Sherwin, 2012).…”

New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection

“…Silverman et al [142] RCT E2 Higher metabolism in language processing and auditory association areas compared to other HRT regimens (CEE or CEE + MPA)…”