Format

Send to

Choose Destination
Neurology. 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.

Author information

1
From the Departments of Health Research & Policy (Epidemiology) and Neurology & Neurological Sciences (V.W.H.), Stanford University; Atherosclerosis Research Unit (J.A.S., H.N.H., N.K., L.D., H.A., W.J.M.) and Departments of Preventive Medicine (J.A.S., H.N.H., F.Z.S., N.K., L.D., H.A., W.J.M.), Medicine (H.N.H.), Neurology (C.A.M.), and Obstetrics and Gynecology (F.Z.S., D.S.), Keck School of Medicine, and Department of Molecular Pharmacology and Toxicology, School of Pharmacy (H.N.H.), University of Southern California, Los Angeles. vhenderson@stanford.edu.
2
From the Departments of Health Research & Policy (Epidemiology) and Neurology & Neurological Sciences (V.W.H.), Stanford University; Atherosclerosis Research Unit (J.A.S., H.N.H., N.K., L.D., H.A., W.J.M.) and Departments of Preventive Medicine (J.A.S., H.N.H., F.Z.S., N.K., L.D., H.A., W.J.M.), Medicine (H.N.H.), Neurology (C.A.M.), and Obstetrics and Gynecology (F.Z.S., D.S.), Keck School of Medicine, and Department of Molecular Pharmacology and Toxicology, School of Pharmacy (H.N.H.), University of Southern California, Los Angeles.

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.

PMID:
27421538
PMCID:
PMC4999165
DOI:
10.1212/WNL.0000000000002980
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center