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


Silverman, Daniel H. S., Geist, Cheri L., Kenna, Heather A., Williams, Katherine, Wroolie, Tonita, Powers, Bevin, Brooks, John, Rasgon, Natalie L.


Psychoneuroendocrinology, Volume: 36, No.: 4, Pages.: 502-513

Year of Publication



Differential 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 was to 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 three 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.; Copyright © 2010 Elsevier Ltd. All rights reserved.

Bibtex Citation

@article{Silverman_2011, doi = {10.1016/j.psyneuen.2010.08.002}, url = {}, year = 2011, month = {may}, publisher = {Elsevier {BV}}, volume = {36}, number = {4}, pages = {502--513}, author = {Daniel H.S. Silverman and Cheri L. Geist and Heather A. Kenna and Katherine Williams and Tonita Wroolie and Bevin Powers and John Brooks and Natalie L. Rasgon}, title = {Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for {AD}}, journal = {Psychoneuroendocrinology} }


administration & dosage, aged, alzheimer disease, brain, brain chemistry, chemistry pharmaceutical, diagnostic use, drug effects, estradiol, estrogen replacement therapy, estrogens conjugated usp, etiology, female, fluorodeoxyglucose f18, humans, menopausal, metabolism, methods, middle aged, neuropsychological tests, organ specificity, pharmacology, physiology, post, postmenopause, prevention & control, progesterone, psychology, radionuclide imaging, risk factors, women

Countries of Study


Types of Dementia

Alzheimer’s Disease

Type of Outcomes

Prevention and/or management of co-morbidities

Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population

Diagnostic Targets

Neuroimaging (e.g. MRI, PET, CAT etc.)