A double-blind, placebo-controlled trial of donepezil for the treatment of menopause-related cognitive loss

Background: Perimenopausal and menopausal women are more likely to complain of memory loss than are premenopausal women, although the association between menopause and cognitive loss remains controversial. Recently published studies on the risks of hormone therapy have left many women and their physicians seeking effective nonhormonal treatments for menopausal symptoms, including cognitive loss. Objective: This study investigated the efficacy of the cholinesterase agent donepezil in the treatment of menopause-related cognitive loss. Methods: Community-dwelling women in natural menopause were recruited for a randomized, double-blind, placebo-controlled study of donepezil. To qualify for enrollment, the Brief Cognitive Rating Scale was used to determine cognitive symptoms, and women with depression were excluded. Subjects were randomized to receive either donepezil, commencing at 5 mg/d, or placebo. At week 6 of randomization, the dosage of donepezil was increased to 10 mg/d. Treatment continued throughout the 26-week study. The primary outcome measure was the overall change in neurocognitive test results over time. Outcome variables. of test scores were analyzed before and after receipt of donepezil or placebo. Results: A total of 28 women aged 46 to 60 years were enrolled. Fourteen women were randomized to receive active drug, 14 to placebo. Two women dropped out of the placebo group. There were no statistically significant differences between treatment groups in post-/pre-dose mean score ratios. No interactions were statistically significant. The P values for tests of equal variances did not reveal a difference in the means. Subjective measures did show some trends toward improvement in memory and cognition. Conclusion: Donepezil was no more effective than placebo in treating the symptoms of menopauserelated memory and cognitive loss. (Gend Med. 2007;4:352-358) Copyright (c) 2007 Excerpta Medica, Inc.