title: Effects of hormone therapy on brain structure: A randomized controlled trial.
abstract: OBJECTIVE
  To investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women.
  
  
  METHODS
  Participants (aged 42-56 years, within 5-36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured.
  
  
  RESULTS
  Higher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = -0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups.
  
  
  CONCLUSIONS
  Ventricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation.
  
  
  METHODS
  This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo.
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison. kantarci.kejal@mayo.edu.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Nirubol
authors.initials: N
authors.lastname: Tosakulwong
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Zuk
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Carey E
authors.initials: CE
authors.lastname: Gleason
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Whitney
authors.initials: W
authors.lastname: Wharton
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: N Maritza
authors.initials: NM
authors.lastname: Dowling
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Lynne T
authors.initials: LT
authors.lastname: Shuster
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Rocca
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Asthana
authors.affiliation: From the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004333:Drug Administration Routes; D004967:Estrogens / Q000008:administration & dosage* / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D009483:Neuropsychological Tests; D012189:Retrospective Studies
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP)