Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease - A randomized controlled trial

Context Several reports from small clinical trials have suggested that estr ogen replacement therapy may be useful for the treatment of Alzheimer disea se (AD) in women. Objective To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. Design The Alzheimer's Disease Cooperative Study, a randomized, double-blin d, placebo-controlled clinical trial conducted between October 1995 and Jan uary 1999. Setting Thirty-two study sites in the United States. Participants A total of 120 women with mild to moderate AD and a Mini-Menta l State Examination score between 12 and 28 who had had a hysterectomy. Interventions 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 su bjects completed the trial. Main Outcome Measures The primary outcome measure was change on the Clinica l Global Impression of Change (CGIC) 7-point scale, analyzed by intent to t reat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and langua ge), motor function, and activities of daily living; compared by the combin ed estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follo w-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 wor sened (P = .48). Secondary outcome measures also showed no significant diff erences, with the exception of the Clinical Dementia Rating Scale, which su ggested 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 pr ogression nor did it improve global, cognitive, or functional outcomes in w omen with mild to moderate AD. The study does not support the role of estro gen for the treatment of this disease. The potential role of estrogen in th e prevention of AD, however, requires further research.