title: Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study.
abstract: BACKGROUND
  Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women.
  
  
  OBJECTIVE
  To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD.
  
  
  METHODS
  The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999.
  
  
  METHODS
  Thirty-two study sites in the United States.
  
  
  METHODS
  A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy.
  
  
  METHODS
  Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial.
  
  
  METHODS
  The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up.
  
  
  RESULTS
  The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01).
  
  
  CONCLUSIONS
  Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.
authors.affiliation: Institute for Brain Aging and Dementia, University of California, Irvine 92697-4540, USA. ramulnar@uci.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Mulnard
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
authors.forename: C
authors.initials: C
authors.lastname: Kawas
authors.forename: C H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.forename: R
authors.initials: R
authors.lastname: Doody
authors.forename: E
authors.initials: E
authors.lastname: Koss
authors.forename: E
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: S
authors.initials: S
authors.lastname: Jin
authors.forename: A
authors.initials: A
authors.lastname: Gamst
authors.forename: M
authors.initials: M
authors.lastname: Grundman
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: L J
authors.initials: LJ
authors.lastname: Thal
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D016014:Linear Models; D008609:Mental Status Schedule; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D004966:Estrogens, Conjugated (USP)