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Randomized Controlled Trial
. 2016 Aug 16;87(7):699-708.
doi: 10.1212/WNL.0000000000002980. Epub 2016 Jul 15.

Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis

Victor W Henderson  1 , Jan A St John  2 , Howard N Hodis  2 , Carol A McCleary  2 , Frank Z Stanczyk  2 , Donna Shoupe  2 , Naoko Kono  2 , Laurie Dustin  2 , Hooman Allayee  2 , Wendy J Mack  2
Affiliations
Randomized Controlled Trial

Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis

Victor W Henderson et al. Neurology. .

Abstract

Objective: To test the hypothesis that effects of estrogen-containing hormone therapy on cognitive abilities differ between postmenopausal women near to, and further from, menopause.

Methods: In this randomized, double-blind, placebo-controlled trial, healthy women within 6 years of menopause or 10+ years after menopause were randomly assigned to oral 17β-estradiol 1 mg/d or placebo. Women with a uterus received cyclic micronized progesterone vaginal gel or placebo. The primary outcome assessed at 2.5 and 5 years, compared between treatment groups, was change in a standardized composite of neuropsychological test scores assessing verbal episodic memory. Secondary outcomes assessed executive functions and global cognition.

Results: A total of 567 women were included in modified intention-to-treat analyses after a mean treatment duration of 57 months. For verbal memory, the mean estradiol minus placebo standardized difference in composite scores (-0.06, 95% confidence interval -0.22 to 0.09) was not significant (2-tailed p = 0.33). Differences were similar in early and late postmenopause groups (2-tailed interaction p = 0.88). Interactions between postmenopause groups and differences between treatment groups were not significant for executive functions or global cognition.

Conclusions: Estradiol initiated within 6 years of menopause does not affect verbal memory, executive functions, or global cognition differently than therapy begun 10+ years after menopause. Estradiol neither benefits nor harms these cognitive abilities regardless of time since menopause.

Classification of evidence: This study provides Class I evidence that estradiol initiated within 6 years of menopause does not affect cognition at 2.5 years differently than estradiol initiated 10+ years after menopause.

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Figures

Figure
Figure. Flowchart of study enrollment and follow-up
Suspected study-related adverse events and other reasons for participant discontinuation are given in the e-Results.
See this image and copyright information in PMC

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