{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:14:25Z","timestamp":1788444865265,"version":"build-2803163510"},"reference-count":27,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,5,21]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Genitourinary syndrome of menopause (GSM) is a chronic, oestrogen-deficient condition that is frequently underdiagnosed and undertreated. Although low-dose vaginal estriol improves epithelial trophism and microbial balance, a substantial proportion of women report persistent symptoms. High-quality randomised evidence evaluating combined therapeutic strategies remains scarce. Energy-based modalities, including the erbium:YAG (Er:YAG) laser (\u03bb=2940\u2009nm), have been proposed as adjunctive treatments. This trial aims to assess the efficacy of Er:YAG laser therapy combined with vaginal estriol compared with estriol alone in postmenopausal women with GSM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This is a single-centre, randomised, double-blind, controlled clinical trial. Postmenopausal women aged 45\u201370 years with vaginal pH \u22655.0\u2009and at least one moderate GSM symptom (Visual Analogue Scale \u22654) will be eligible. Exclusion criteria include current systemic or local hormone therapy, previous vaginal energy-based treatment, abnormal cervical cytology and body mass index \u226535\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . All participants will receive vaginal estriol cream (0.5\u2009mg per dose) daily for 14 days, followed by twice-weekly administration for 16 weeks. Participants will be randomised (1:1) to receive either estriol plus sham Er:YAG laser or estriol plus active Er:YAG laser. Three laser sessions will be delivered at approximately 4-week intervals. Assessments will occur at baseline, monthly during treatment and 4\u2009months after the final session. The primary outcome is the Vulvovaginal Health Index, with the primary endpoint defined as the change from baseline to 4\u2009months post-treatment, reflecting sustained effect. Secondary outcomes include GSM symptom severity, vaginal microbiome composition (16S rRNA sequencing), quality of life (Menopause Rating Scale) and sexual function (Female Sexual Function Index). Data will be analysed using repeated-measures analysis of variance or appropriate non-parametric tests, 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>Ethical approval has been obtained from the Human Research Ethics Committee of UNINOVE. Written informed consent will be obtained. Findings will be disseminated via peer-reviewed journals and scientific meetings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06873971\">NCT06873971<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-117269","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T18:00:27Z","timestamp":1781200827000},"page":"e117269","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Erbium:YAG laser combined with vaginal estriol therapy in postmenopausal women with Genitourinary Syndrome of Menopause: protocol for a randomised, double-blind, controlled trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06873971","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06873971","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2033-5919","authenticated-orcid":false,"given":"M\u00f4nica Cristina da Costa Drago","family":"Souza","sequence":"first","affiliation":[{"name":"Postgraduation Program in Medicine Biophotonics, UNINOVE, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-3023","authenticated-orcid":false,"given":"Zsuzsanna I K","family":"de J\u00e1rmy-Di Bella","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4326-7488","authenticated-orcid":false,"given":"Ana Maria H M","family":"Bianchi-Ferraro","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Escola Paulista de Medicina (EPM), Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0518-8391","authenticated-orcid":false,"given":"Sophia Drago Lima","family":"Souza","sequence":"additional","affiliation":[{"name":"Undergraduate Program in Medicine, Pontif\u00edcia Universidade Cat\u00f3lica de S\u00e3o Paulo, Sorocaba, Sorocaba, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-6725","authenticated-orcid":false,"given":"Mandetta","family":"Amanda Rafaelly Hon\u00f3rio","sequence":"additional","affiliation":[{"name":"Postgraduation Program in Medicine Biophotonics, UNINOVE, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6846-6574","authenticated-orcid":false,"given":"Ana Paula Taboada","family":"Sobral","sequence":"additional","affiliation":[{"name":"Postgraduation Program in Health and Environment, Universidade Metropolitana de Santos, Santos, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-9333","authenticated-orcid":false,"given":"Caroline Diniz Pagani Vieira","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Postgraduation Program in Medicine Biophotonics, UNINOVE, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-1138","authenticated-orcid":false,"given":"Sandra Kalil","family":"Bussadori","sequence":"additional","affiliation":[{"name":"Postgraduation Program in Medicine Biophotonics, 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