{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:46:37Z","timestamp":1767797197278,"version":"3.49.0"},"reference-count":30,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"unspecified","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1195709"],"award-info":[{"award-number":["APP1195709"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,11,29]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation technique that has been shown to improve cognition and mood when applied to certain brain structures and regions. Despite research demonstrating that iTBS may have clinical utility in treating cognitive and mood changes, no study has yet been conducted to explore the potential to modulate the neurophysiological changes that can underpin cognitive and mood changes during the menopause transition. Cognitive and psychological symptoms are commonly reported by females experiencing the menopause transition, and it is thought that these symptoms arise due to various neurophysiological, metabolic and endocrinological changes. Despite being common, there is a lack of treatments available for managing these symptoms and a scarcity of data regarding the mechanisms by which they occur.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      The aim of this 5-week randomised, sham-controlled, double-blinded pilot clinical trial (n=72) is to assess the underlying mechanisms of action of iTBS in females in the late menopause transition and the relationship with cognition and mood. Data will be analysed using Stata\n                      <jats:sup>TM<\/jats:sup>\n                      . Normality checks will guide the choice between parametric and non-parametric tests. Generalised linear models will assess within-subject and between-subject effects across timepoints, with additional regression analyses exploring associations between biomarkers, cognition and mood. Effect sizes, CIs and relevant test statistics will be reported, with significance set at p&lt;0.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study protocol has been reviewed and ethically approved by the Western Sydney University Human Research Ethics Committee (H16200; 8 November 2024). All participants will provide written informed consent prior to enrolment. Results from this trial will be disseminated via peer-reviewed publications and conference presentations, with findings shared in accordance with open science and data transparency principles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ANZCTR registration number<\/jats:title>\n                    <jats:p>ACTRN12625000030471, Australian New Zealand Clinical Trials Registry<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-106745","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T11:50:26Z","timestamp":1766145026000},"page":"e106745","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["The MenoStim Trial: Study Protocol for a Randomised, Sham-Controlled, Double-Blinded, Pilot Clinical Trial Exploring the Neurophysiological, Cognitive, Mood and Biochemical Effects Associated with Non-Invasive Brain Stimulation During the Menopause Transition"],"prefix":"10.1136","volume":"15","author":[{"given":"Najwa-Joelle","family":"Metri","sequence":"first","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia"},{"name":"Brain Stimulation and Rehabilitation (BrainStAR Lab), School of Health Sciences, Western Sydney University, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9499-1703","authenticated-orcid":false,"given":"Rocco","family":"Cavaleri","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia"},{"name":"Brain Stimulation and Rehabilitation (BrainStAR Lab), School of Health Sciences, Western Sydney University, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghufran","family":"Alhassani","sequence":"additional","affiliation":[{"name":"Brain Stimulation and Rehabilitation (BrainStAR Lab), School of Health Sciences, Western Sydney University, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Ee","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia"},{"name":"Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chai K","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Jena University Hospital, Jena, Germany"},{"name":"German Centre for Mental Health (DZPG), Partner Site Jena, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather M.","family":"Francis","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences, Macquarie University, Macquarie Park, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Hochstrasser","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rose Mery","family":"Bou Merhy","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia"},{"name":"Brain Stimulation and Rehabilitation (BrainStAR Lab), School of Health Sciences, Western Sydney University, Sydney, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-6104","authenticated-orcid":false,"given":"Genevieve Z","family":"Steiner-Lim","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia"},{"name":"German Centre for Mental Health (DZPG), Partner Site Jena, Jena, Germany"},{"name":"Translational Health Research Institute (THRI), Western Sydney University, Penrith, NSW, Australia"},{"name":"Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"2026010703492289000_15.12.e106745.1","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2021.1892627"},{"key":"2026010703492289000_15.12.e106745.2","first-page":"e1404","article-title":"Brain structure and cognition 3 years after the end of an early menopausal hormone therapy trial","volume":"90","author":"Kantarci","year":"2018","journal-title":"Neurology (ECronicon)"},{"key":"2026010703492289000_15.12.e106745.3","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s40266-013-0100-1","article-title":"Depression in Peri- and Postmenopausal Women: Prevalence, Pathophysiology and Pharmacological Management","volume":"30","author":"Soares","year":"2013","journal-title":"Drugs Aging"},{"key":"2026010703492289000_15.12.e106745.4","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-90084-y","article-title":"Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition","volume":"11","author":"Mosconi","year":"2021","journal-title":"Sci Rep"},{"key":"2026010703492289000_15.12.e106745.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0185926","article-title":"Perimenopause and emergence of an Alzheimer\u2019s bioenergetic phenotype in brain and periphery","volume":"12","author":"Mosconi","year":"2017","journal-title":"PLoS One"},{"key":"2026010703492289000_15.12.e106745.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.03.013"},{"key":"2026010703492289000_15.12.e106745.7","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.5665\/sleep.1398","article-title":"Evaluation of the association of menopausal status with delta and beta EEG activity during sleep","volume":"34","author":"Campbell","year":"2011","journal-title":"Sleep"},{"key":"2026010703492289000_15.12.e106745.8","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2024.1350318","article-title":"Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition","volume":"15","author":"Andy","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026010703492289000_15.12.e106745.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.08.020"},{"key":"2026010703492289000_15.12.e106745.10","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2022.984708","article-title":"Effects of rTMS treatment on global cognitive function in Alzheimer\u2019s disease: A systematic review and meta-analysis","volume":"14","author":"Zhang","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"2026010703492289000_15.12.e106745.11","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291713000512"},{"key":"2026010703492289000_15.12.e106745.12","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-020-01055-2","article-title":"Recovering from depression with repetitive transcranial magnetic stimulation (rTMS): a systematic review and meta-analysis of preclinical studies","volume":"10","author":"De Risio","year":"2020","journal-title":"Transl Psychiatry"},{"key":"2026010703492289000_15.12.e106745.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-11-04079.1988"},{"key":"2026010703492289000_15.12.e106745.14","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1080\/02699052.2024.2344087","article-title":"The effect of intermittent theta burst stimulation for cognitive dysfunction: a meta-analysis","volume":"38","author":"Zheng","year":"2024","journal-title":"Brain Inj"},{"key":"2026010703492289000_15.12.e106745.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02630-5"},{"key":"2026010703492289000_15.12.e106745.16","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1210\/jc.2011-3362","article-title":"Executive Summary of the Stages of Reproductive Aging Workshop + 10: Addressing the Unfinished Agenda of Staging Reproductive Aging","volume":"97","author":"Harlow","year":"2012","journal-title":"The Journal of Clinical Endocrinology & Metabolism"},{"key":"2026010703492289000_15.12.e106745.17","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1212\/WNL.0b013e3181a71193","article-title":"Effects of the menopause transition and hormone use on cognitive performance in midlife women","volume":"72","author":"Greendale","year":"2009","journal-title":"Neurology (ECronicon)"},{"key":"2026010703492289000_15.12.e106745.18","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.psyneuen.2008.03.006","article-title":"Effect of age, gender, menopausal status, and ovarian hormonal level on rTMS in treatment-resistant depression","volume":"33","author":"Huang","year":"2008","journal-title":"Psychoneuroendocrinology"},{"key":"2026010703492289000_15.12.e106745.19","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.brs.2012.10.009","article-title":"Effect of two weeks of rTMS on brain activity in healthy subjects during an n-back task: a randomized double blind study","volume":"6","author":"Gaudeau-Bosma","year":"2013","journal-title":"Brain Stimul"},{"key":"2026010703492289000_15.12.e106745.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2010.06.012"},{"key":"2026010703492289000_15.12.e106745.21","unstructured":"Mann SK , Malhi NK . Repetitive transcranial magnetic stimulation. 2021."},{"key":"2026010703492289000_15.12.e106745.22","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(94)90029-9"},{"key":"2026010703492289000_15.12.e106745.23","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.jpain.2022.11.013","article-title":"The Effect of Theta Burst Stimulation Over the Primary Motor Cortex on Experimental Hamstring Pain: A Randomized, Controlled Study","volume":"24","author":"Moukhaiber","year":"2023","journal-title":"J Pain"},{"key":"2026010703492289000_15.12.e106745.24","article-title":"A randomized, double\u2010blind, placebo\u2010controlled, parallel\u2010group 12\u2010week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment","volume":"9","author":"Steiner\u2010Lim","year":"2023","journal-title":"Alzheimer\u2019s & Dementia: Translational Research & Clinical Interventions"},{"key":"2026010703492289000_15.12.e106745.25","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-2457(99)00296-5"},{"key":"2026010703492289000_15.12.e106745.26","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1093\/cercor\/bhy171","article-title":"Interrogating the Relationship Between Schizotypy, the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism, and Neuronal Oscillatory Activity","volume":"29","author":"Steiner","year":"2019","journal-title":"Cereb Cortex"},{"key":"2026010703492289000_15.12.e106745.27","doi-asserted-by":"crossref","first-page":"149399","DOI":"10.1016\/j.brainres.2024.149399","article-title":"Eyes-open and eyes-closed EEG of older adults with subjective cognitive impairment versus healthy controls: A frequency principal components analysis study","volume":"1850","author":"Cave","year":"2025","journal-title":"Brain Res"},{"key":"2026010703492289000_15.12.e106745.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00744-x"},{"key":"2026010703492289000_15.12.e106745.29","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.brs.2019.11.009","article-title":"TMS for staging and predicting functional decline in frontotemporal dementia","volume":"13","author":"Benussi","year":"2020","journal-title":"Brain Stimul"},{"key":"2026010703492289000_15.12.e106745.30","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnint.2014.00014","article-title":"The mechanism of dishabituation","volume":"8","author":"Steiner","year":"2014","journal-title":"Front Integr Neurosci"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-106745","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T11:53:51Z","timestamp":1767786831000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-106745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":30,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,19]]},"published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1136\/bmjopen-2025-106745"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-106745","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]}}}