Evidence map›Paper›PMID 27473135›Full record

Trial reportNeurology2016

Effects of hormone therapy on brain structure: A randomized controlled trial.

Kejal Kantarci, Nirubol Tosakulwong, Timothy G Lesnick, Samantha M Zuk, Jeffrey L Gunter, Carey E Gleason, Whitney Wharton, N Maritza Dowling, Prashanthi Vemuri, Matthew L Senjem and 6 more

Open access · hybridAbstract readMulticenter StudyRandomized 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. Cited by 38 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 4 pooled it
4.5field-weighted citation impact, top 5% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 4 syntheses or guidelines pooled it, 74 citations in OpenAlex.

  1. Brazilian Guideline on Menopausal Cardiovascular Health - 2024.Arquivos brasileiros de cardiologia · 2024
    Guideline
  2. Pooled it
  3. Pooled it
  4. Long-term hormone therapy for perimenopausal and postmenopausal women.The Cochrane database of systematic reviews · 2017
    Pooled it
  5. Trial
  6. Trial
  7. Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback.American journal of physiology. Regulatory, integrative and comparative physiology · 2019
    Trial
  8. Trial
  9. Trial
  10. Review
  11. Hormone replacement therapy and its association with LATE-NC in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Brazilian Guideline on Menopausal Cardiovascular Health - 2024.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2024
    Article
  19. Article
  20. Article
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

16 authors at 3 institutions in 1 country.

Kejal KantarciFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison. kantarci.kejal@mayo.edu.
Nirubol TosakulwongFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Timothy G LesnickFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Samantha M ZukFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Jeffrey L GunterFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Carey E GleasonFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Whitney WhartonFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
N Maritza DowlingFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Prashanthi VemuriFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Matthew L SenjemFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Lynne T ShusterFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Kent R BaileyFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Walter A RoccaFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Clifford R JackFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Sanjay AsthanaFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Virginia M MillerFrom the Departments of Radiology (K.K., S.M.Z., J.L.G., P.V., M.L.S., C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Internal Medicine (L.T.S.), Neurology (W.A.R.), and Surgery and Physiology and Biomedical Engineering (V.M.M.), Mayo Clinic, Rochester, MN; Department of Medicine (C.E.G., S.A.), School of Medicine and Public Health, University of Wisconsin and Geriatric Research, Education and Clinical Center, William S. Middleton Memorial, Veterans' Hospital, Madison, WI; Department of Neurology (W.W.), Emory University, Atlanta, GA; and Department of Biostatistics and Medical Informatics (N.M.D.), University of Wisconsin, Madison.
Geriatric Research Education and Clinical Center · USEmory University · USWilliam S. Middleton Memorial Veterans Hospital · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Wisconsin Alzheimer's Disease Research CenterP50AG033514 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI SAGER, MARK · 2009 to 2018
$16.2M
PREDICTING ALZHEIMERS DISEASE WITH MAGNETIC RESONANCER01AG011378 · NIA · MAYO CLINIC ROCHESTER · PI JACK, CLIFFORD R. · 1993 to 2017
$12.1M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5U01HL096917 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI MOSLEY, THOMAS H · 2010 to 2018
$11.9M
Sex-specific Risk for Vascular Dysfunction and Cognitive DeclineP50AG044170 · NIA · MAYO CLINIC ROCHESTER · PI MILLER, VIRGINIA M · 2012 to 2017
$6.1M
Imaging CoreU01AG032438 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2008 to 2009
$6.1M
KEEPS Cognitive and Affective StudyR01AG029624 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ASTHANA, SANJAY · 2007 to 2013
$3.4M
Stroke and Cognitive Impairment in Aging Chronic Kidney Disease PatientsR01AG037551 · NIA · HENNEPIN HEALTHCARE RESEARCH INSTITUTE · PI MURRAY, ANNE M · 2011 to 2015
$2.7M
Pathological basis of MRS and DTI changes in neurodegenerative dementiaR01AG040042 · NIA · MAYO CLINIC ROCHESTER · PI KANTARCI, KEJAL · 2011 to 2015
$1.6M
Effects of estrogen on brain morphology and neuronal integrity in early menopauseR21NS066147 · NINDS · MAYO CLINIC ROCHESTER · PI KANTARCI, KEJAL · 2010 to 2011
$405k
NHLBI NIH HHS U01 HL096917NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG044170NIA NIH HHS R01 AG011378NIA NIH HHS R01 AG029624NIA NIH HHS R01 AG037551NIA NIH HHS R01 AG040042NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032438NINDS NIH HHS R21 NS066147
6 · The paper itself

Abstract

objectiveTo investigate the effects of hormone therapy on brain structure in a randomized, double-blinded, placebo-controlled trial in recently postmenopausal women.

methodsParticipants (aged 42-56 years, within 5-36 months past menopause) in the Kronos Early Estrogen Prevention Study were randomized to (1) 0.45 mg/d oral conjugated equine estrogens (CEE), (2) 50 μg/d transdermal 17β-estradiol, or (3) placebo pills and patch for 48 months. Oral progesterone (200 mg/d) was given to active treatment groups for 12 days each month. MRI and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization (n = 95). Changes in whole brain, ventricular, and white matter hyperintensity volumes, and in global cognitive function, were measured.

resultsHigher rates of ventricular expansion were observed in both the CEE and the 17β-estradiol groups compared to placebo; however, the difference was significant only in the CEE group (p = 0.01). Rates of ventricular expansion correlated with rates of decrease in brain volume (r = -0.58; p ≤ 0.001) and with rates of increase in white matter hyperintensity volume (r = 0.27; p = 0.01) after adjusting for age. The changes were not different between the CEE and 17β-estradiol groups for any of the MRI measures. The change in global cognitive function was not different across the groups.

conclusionsVentricular volumes increased to a greater extent in recently menopausal women who received CEE compared to placebo but without changes in cognitive performance. Because the sample size was small and the follow-up limited to 4 years, the findings should be interpreted with caution and need confirmation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that brain ventricular volume increased to a greater extent in recently menopausal women who received oral CEE compared to placebo.

Indexed as

AdultBrainCerebral VentriclesCognitionDouble-Blind MethodDrug Administration RoutesEstrogensEstrogens, Conjugated (USP)FemaleHumansImaging, Three-DimensionalLongitudinal StudiesMagnetic Resonance ImagingMenopauseMiddle AgedNeuropsychological TestsEstrogensEstrogens, Conjugated (USP)

Identifiers

PMID27473135
PMCPMC5035155
OpenAlexW2480704615

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.