title: Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition.
abstract: It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer's disease (AD).
  
  
  
  To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women.
  
  
  
  Participants within 5-36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated.
  
  
  
  Women (age = 52-65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11-0.83)]. In the APOEɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004-0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006-0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOEɛ4 non-carriers.
  
  
  
  In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOEɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample.
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Nirubol
authors.initials: N
authors.lastname: Tosakulwong
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Fields
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lynne T
authors.initials: LT
authors.lastname: Shuster
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Zuk
authors.affiliation: Department of Information Technology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.|Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Department of Medicine, School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center (GRECC) William S. Middleton Memorial, Veterans' Hospital, Madison, WI, USA.
authors.forename: Carey
authors.initials: C
authors.lastname: Gleason
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.|Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Rocca
authors.affiliation: Departments of Surgery, Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology*; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism*; D012189:Retrospective Studies; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D001057:Apolipoproteins E; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D013844:Thiazoles; D004958:Estradiol
keywords: Alzheimer’s disease; PET; amyloid-β; cognitive function; estrogen; hormone therapy; menopause; prevention