title: Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes.
abstract: OBJECTIVE
  To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial.
  
  
  METHODS
  The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes.
  
  
  RESULTS
  Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p=0.002). This interaction was evident for total gray matter (p<0.001) and hippocampal (p=0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications.
  
  
  CONCLUSIONS
  For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women.
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD. mespelan@wakehealth.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Espeland
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Roberta Diaz
authors.initials: RD
authors.lastname: Brinton
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Christina
authors.initials: C
authors.lastname: Hugenschmidt
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Leslie
authors.initials: L
authors.lastname: Vaughan
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craft
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Beatrice J
authors.initials: BJ
authors.lastname: Edwards
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Ramon
authors.initials: R
authors.lastname: Casanova
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Kamal
authors.initials: K
authors.lastname: Masaki
authors.affiliation: From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D017698:Postmenopause / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic
chemical_list: D004966:Estrogens, Conjugated (USP)