Trial reportNeurology2018
Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial.
Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 3 pooled it
5.9field-weighted citation impact, top 3% of its field
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.
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.
Who cites it
55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Reproductive life stages and cognitive outcomes: a systematic review in Latin American and Caribbean women.Frontiers in aging neuroscience · 2026Pooled it
- The historical progression of positron emission tomography research in neuroendocrinology.Frontiers in neuroendocrinology · 2023Pooled it
- Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.Frontiers in aging neuroscience · 2023Pooled it
- Long-term cognitive effects of menopausal hormone therapy: Findings from the KEEPS Continuation Study.PLoS medicine · 2024Trial
- Menopausal hormone therapy, blood thrombogenicity, and development of white matter hyperintensities in women of the Kronos Early Estrogen Prevention Study.Menopause (New York, N.Y.) · 2020Trial
- Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Trial
- Safety and feasibility of estrogen receptor-β targeted phytoSERM formulation for menopausal symptoms: phase 1b/2a randomized clinical trial.Menopause (New York, N.Y.) · 2019Trial
- Greater temporo-occipital gray matter volume and frontoparietal cortical thickness in post-menopausal women: a UK Biobank study.Brain structure & function · 2026Article
- Menopause and neurological disorders: a roadmap for research.Nature reviews. Neurology · 2026Review
- Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Reproductive lifespan and hormonal therapy in relation to later-life neurovascular health: A population-based study of women in the Gothenburg H70-1944 Birth Cohort.medRxiv : the preprint server for health sciences · 2026Article
- Sex-dependent grey matter atrophy in Alzheimer's disease progression.Brain communications · 2026Article
- Menopausal hormone therapy and risk of neuropsychiatric disease: a drug target Mendelian randomisation study.npj women's health · 2026Article
- Chronological age is differentially associated with cognitive performance according to climacteric stage: evidence from a Bayesian multivariate analysis in Chilean women.Frontiers in psychology · 2026Article
- CSF estrogens' relationships to neuroinflammatory markers and brain networks in middle-aged and older black and white women.Journal of neuroinflammation · 2025Article
- Article
- Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome.bioRxiv : the preprint server for biology · 2025Article
- Association Between Menopause Age and Estradiol-Based Hormone Therapy With Cognitive Performance in Cognitively Normal Women in the CLSA.Neurology · 2025Observational
- Cognitive strategy in verbal fluency: sex differences, menstrual cycle, and menopause effects.Cognitive processing · 2025Article
- Hypertension in Pregnancy Linked to Cerebral Small Vessel Disease 15 Years Later.Hypertension (Dallas, Tex. : 1979) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Kejal KantarciFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC. kantarci.kejal@mayo.edu.
Nirubol TosakulwongFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Timothy G LesnickFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Samantha M ZukFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Val J LoweFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Julie A FieldsFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Jeffrey L GunterFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Matthew L SenjemFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Megan L SettellFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Carey E GleasonFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Lynne T ShusterFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Kent R BaileyFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
N Maritza DowlingFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Sanjay AsthanaFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Clifford R JackFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Walter A RoccaFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
Virginia M MillerFrom the Departments of Radiology (K.K., S.M.Z., V.J.L., J.L.G., M.L. Senjem, M.L. Settell, C.R.J.), Health Sciences Research (N.T., T.G.L., K.R.B., W.A.R.), Psychology and Psychiatry (J.A.F.), 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; and Department of Biostatistics (N.M.D.), George Washington University, Washington, DC.
William S. Middleton Memorial Veterans Hospital · USGeriatric Research Education and Clinical Center · US
Funding
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9MPrevention of Alzheimer's disease in women: risks and benefits of hormone therapyRF1AG057547 · NIA · MAYO CLINIC ROCHESTER · PI GLEASON, CAREY E, KANTARCI, KEJAL · 2017 to 2020
$11.1MSex-Specific Effects of Endocrine Disruption on Aging and Alzheimer's DiseaseU54AG044170 · NIA · MAYO CLINIC ROCHESTER · PI KAPOOR, EKTA · 2018 to 2022
$7.7MSex-specific Risk for Vascular Dysfunction and Cognitive DeclineP50AG044170 · NIA · MAYO CLINIC ROCHESTER · PI MILLER, VIRGINIA M · 2012 to 2017
$6.1MNRSA Training CoreTL1TR002380 · NCATS · MAYO CLINIC ROCHESTER · PI Felicity T. B. Enders, ANTHONY John WINDEBANK · 2017 to 2026
$6.0MKEEPS Cognitive and Affective StudyR01AG029624 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ASTHANA, SANJAY · 2007 to 2013
$3.4MEffects of estrogen on brain morphology and neuronal integrity in early menopauseR21NS066147 · NINDS · MAYO CLINIC ROCHESTER · PI KANTARCI, KEJAL · 2010 to 2011
$405kNCATS NIH HHS TL1 TR002380NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG044170NIA NIH HHS R01 AG029624NIA NIH HHS RF1 AG057547NIA NIH HHS U54 AG044170NINDS NIH HHS R21 NS066147
Abstract
objectiveThe effects of 2 frequently used formulations of menopausal hormone therapy (mHT) on brain structure and cognition were investigated 3 years after the end of a randomized, placebo-controlled trial in recently menopausal women with good cardiovascular health.
methodsParticipants (aged 42-56 years; 5-36 months past menopause) were randomized to one of the following: 0.45 mg/d oral conjugated equine estrogen (oCEE); 50 μg/d transdermal 17β-estradiol (tE2); or placebo pills and patch for 4 years. Oral progesterone (200 mg/d) was given to mHT groups for 12 days each month. MRIs were performed at baseline, at the end of 4 years of mHT, and 3 years after the end of mHT (n = 75). A subset of participants also underwent Pittsburgh compound B-PET (n = 68).
resultsVentricular volumes increased more in the oCEE group compared to placebo during the 4 years of mHT, but the increase in ventricular volumes was not different from placebo 3 years after the discontinuation of mHT. Increase in white matter hyperintensity volume was similar in the oCEE and tE2 groups, but it was statistically significantly greater than placebo only in the oCEE group. The longitudinal decline in dorsolateral prefrontal cortex volumes was less in the tE2 group compared to placebo, which correlated with lower cortical Pittsburgh compound B uptake. Rates of global cognitive change in mHT groups were not different from placebo.
conclusionsThe effects of oCEE on global brain structure during mHT subside after oCEE discontinuation but white matter hyperintensities continue to increase. The relative preservation of dorsolateral prefrontal cortical volume in the tE2 group over 7 years indicates that mHT may have long-term effects on the brain. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the rates of change in global brain volumes and cognitive function in recently menopausal women receiving mHT (tE2 or oCEE) were not significantly different from women receiving placebo, as measured 3 years after exposure to mHT.
Indexed as
BrainCognitionEstrogensHormone Replacement TherapyPostmenopauseAdultAniline CompoundsDouble-Blind MethodHumansLongitudinal StudiesMagnetic Resonance ImagingMiddle AgedNeuropsychological TestsPositron-Emission TomographyThiazoles2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazoleAniline CompoundsEstrogensThiazoles
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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 Socratic graph.