title: Change in brain and lesion volumes after CEE therapies: the WHIMS-MRI studies.
abstract: OBJECTIVE
  To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2.
  
  
  METHODS
  A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures.
  
  
  RESULTS
  Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88).
  
  
  CONCLUSIONS
  Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.
authors.affiliation: From the Division of Public Health Sciences (L.H.C., M.A.E., P.E.H., S.A.S.), and Departments of Internal Medicine and Geriatrics (J.D.W.) and Neurology (C.D.B.), Wake Forest School of Medicine, Winston-Salem, NC; Intramural Research Program (S.M.R.), National Institute on Aging, NIH, Baltimore, MD; Department of Radiology (R.N.B., C.D.), University of Pennsylvania, Philadelphia; Department of Internal Medicine and Epidemiology (J.G.R.), University of Iowa, Iowa City; Department of Psychiatry and Behavioral Medicine (J.S.G.), Medical College of Wisconsin, Milwaukee; and Department of Epidemiology (L.H.K.), University of Pittsburgh, PA.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Coker
authors.forename: Mark A
authors.initials: MA
authors.lastname: Espeland
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Hogan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: R Nick
authors.initials: RN
authors.lastname: Bryan
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Bushnell
authors.forename: Sally A
authors.initials: SA
authors.lastname: Shumaker
mesh_terms: D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods / Q000639:trends*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000639:trends*; D008875:Middle Aged; D009929:Organ Size; D016387:Women's Health / Q000639:trends*
chemical_list: D004966:Estrogens, Conjugated (USP)