Hormone replacement therapy in postmenopausal women with Alzheimer's disease: A randomized, prospective study

Objective: To compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimer's disease. Design: Six-month, randomized, open-label study. Setting: University hospital. Patient(s): Fifty-five women with mild to moderate Alzheimer's disease were randomly assigned to tacrine (n = 26) or HRT (n = 29). Intervention(s): In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26). Main Outcome Measure(s): Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL). Result(s): Thirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in ε4-negative patients. Conclusion(s): Overall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In ε4-negative patients, tacrine is preferable for cognition and mood.