title: Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia.
abstract: The objective of this study was to examine the effects of estrogen-based hormone therapy (HT) on regional cerebral metabolism in postmenopausal women (mean age = 58, SD = 5) at risk for development of dementia. The prospective clinical trial design included pre- and post-intervention neuroimaging of women randomized to continue (HT+) or discontinue (HT-) therapy following an average of 10 years of use. The primary outcome measure was change in brain metabolism during the subsequent two years, as assessed with fluorodeoxyglucose-18 positron emission tomography (FDG-PET). Longitudinal FDG-PET data were available for 45 study completers. Results showed that women randomized to continue HT experienced relative preservation of frontal and parietal cortical metabolism, compared with women randomized to discontinue HT. Women who discontinued 17-β estradiol (17βE)-based HT, as well as women who continued conjugated equine estrogen (CEE)-based HT, exhibited significant decline in metabolism of the precuneus/posterior cingulate cortical (PCC) area. Significant decline in PCC metabolism was additionally seen in women taking concurrent progestins (with either 17βE or CEE). Together, these findings suggest that among postmenopausal subjects at risk for developing dementia, regional cerebral cortical metabolism is relatively preserved for at least two years in women randomized to continue HT, compared with women randomized to discontinue HT. In addition, continuing unopposed 17βE therapy is associated specifically with preservation of metabolism in PCC, known to undergo the most significant decline in the earliest stages of Alzheimer's disease.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00097058.
authors.affiliation: Stanford Center for Neuroscience in Women's Health, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Rasgon
authors.affiliation: UCLA David Geffen School of Medicine, Department of Molecular and Medical Pharmacology, Ahmanson Translational Imaging Division, University of California Los Angeles School of Medicine, Los Angeles, California, United States of America.
authors.forename: Cheri L
authors.initials: CL
authors.lastname: Geist
authors.affiliation: Stanford Center for Neuroscience in Women's Health, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Kenna
authors.affiliation: Stanford Center for Neuroscience in Women's Health, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Tonita E
authors.initials: TE
authors.lastname: Wroolie
authors.affiliation: Stanford Center for Neuroscience in Women's Health, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Williams
authors.affiliation: UCLA David Geffen School of Medicine, Department of Molecular and Medical Pharmacology, Ahmanson Translational Imaging Division, University of California Los Angeles School of Medicine, Los Angeles, California, United States of America.
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Silverman
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D003704:Dementia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015914:Estrogen Replacement Therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011372:Progestins / Q000494:pharmacology; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors
chemical_list: D011372:Progestins; D019788:Fluorodeoxyglucose F18