Evidence map›Paper›PMID 27421538›Full record

Trial reportNeurology2016

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

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

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00114517 (Biologic Response of Menopausal Women to 17B-Estradiol), which is not on this map. Cited by 109 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 8 pooled it
17.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00114517 phase2completednot on this map

Biologic Response of Menopausal Women to 17B-Estradiol

TypeinterventionalSponsorUniversity of Southern CaliforniaRan2004 to 2013Enrolled643ConditionsAtherosclerosisArms17B-estradiol, Placebo
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 8 syntheses or guidelines pooled it, 219 citations in OpenAlex.

  1. Pooled it
  2. Brazilian Guideline on Menopausal Cardiovascular Health - 2024.Arquivos brasileiros de cardiologia · 2024
    Guideline
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  8. Long-term hormone therapy for perimenopausal and postmenopausal women.The Cochrane database of systematic reviews · 2017
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49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Victor W HendersonFrom 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.
Jan A St JohnFrom 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.
Howard N HodisFrom 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.
Carol A McClearyFrom 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.
Frank Z StanczykFrom 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.
Donna ShoupeFrom 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.
Naoko KonoFrom 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.
Laurie DustinFrom 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.
Hooman AllayeeFrom 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.
Wendy J MackFrom 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.
Stanford University · US

Funding

Timing of Menopausal Hormone Therapy across Perimenopause to Menopause Transition: Neuroimmune System in BrainP01AG026572 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERTA EILEEN BRINTON · 2006 to 2026
$53.7M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI GREICIUS, MICHAEL D · 2015 to 2019
$7.9M
NIA NIH HHS P01 AG026572NIA NIH HHS P50 AG047366
6 · The paper itself

Abstract

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

methodsIn 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.

resultsA 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.

conclusionsEstradiol 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.

Indexed as

Memory, EpisodicAgedCognitionDouble-Blind MethodEstradiolEstrogen Replacement TherapyEstrogensExecutive FunctionFollow-Up StudiesHumansMenopauseMiddle AgedPostmenopauseProgesteroneProgestinsVaginal Creams, Foams, and JelliesEstradiolEstrogensProgesteroneProgestinsVaginal Creams, Foams, and Jellies

Identifiers

PMID27421538
PMCPMC4999165
OpenAlexW2465155672

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.