title: Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD.
abstract: 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.
authors.affiliation: UCLA David Geffen School of Medicine, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Clinic, CHS AR-144, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095-6942, USA. dsilver@ucla.edu
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
authors.forename: Cheri L
authors.initials: CL
authors.lastname: Geist
authors.forename: Heather A
authors.initials: HA
authors.lastname: Kenna
authors.forename: Katherine
authors.initials: K
authors.lastname: Williams
authors.forename: Tonita
authors.initials: T
authors.lastname: Wroolie
authors.forename: Bevin
authors.initials: B
authors.lastname: Powers
authors.forename: John
authors.initials: J
authors.lastname: Brooks
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Rasgon
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism / Q000523:psychology; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology; D012307:Risk Factors
chemical_list: D004966:Estrogens, Conjugated (USP); D019788:Fluorodeoxyglucose F18; D011374:Progesterone; D004958:Estradiol
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