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We excluded women with a history or current condition of abnormal uterine bleeding and who were unable to attend a 1\u2010year follow up. Women who expelled the device, removed it for reasons unrelated to vaginal bleeding, or were lost to follow up were discontinued. We collected endometrial biopsies immediately before IUD placement and assessed 20 selected genes using reverse transcription quantitative polymerase chain reaction. Users maintained a uterine bleeding diary for 12\u2009months following IUD insertion. For statistical analysis, participants were categorized into groups with or without vaginal bleeding at 3 and 12\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Women with elevated <jats:italic>CXCL9<\/jats:italic> expression had an 8.15\u2010fold higher likelihood of experiencing vaginal bleeding at 3\u2009months (odds ratio [OR] 8.15, 95% confidence interval [CI] 2.24\u201329.61, <jats:italic>P<\/jats:italic>\u2009=\u20090.001). At 12\u2009months of follow up, women with increased <jats:italic>TIMP1<\/jats:italic> expression had a 2.74\u2010fold higher chance of experiencing vaginal bleeding (OR 2.74, 95% CI 1.08\u20136.95, <jats:italic>P<\/jats:italic>\u2009=\u20090.033). <jats:italic>CXCL9<\/jats:italic>\u2009\u2265\u20091.5 and <jats:italic>IL17<\/jats:italic>A\u2009\u2265\u20090.68 were associated with a higher probability of vaginal bleeding at 3\u2009months, while <jats:italic>TIMP1<\/jats:italic> levels \u22650.943 were linked to an increased risk of bleeding at 12\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Users of the 52\u2010mg hormonal IUD with elevated relative <jats:italic>CXCL9<\/jats:italic> expression face an increased risk of vaginal bleeding at 3\u2010month follow up, whereas those with heightened <jats:italic>TIMP1<\/jats:italic> expression are more likely to experience vaginal bleeding at 12\u2009months.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ijgo.15357","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T13:59:10Z","timestamp":1706795950000},"page":"1199-1209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gene expression associated with vaginal bleeding in women using the 52\u2010mg levonorgestrel hormonal intrauterine device: A prospective study"],"prefix":"10.1002","volume":"165","author":[{"given":"Fl\u00e1via R.","family":"Torelli","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel M.","family":"Rodrigues\u2010Peres","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iscia","family":"Lopes\u2010Cendes","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Bahamondes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medical Sciences University of Campinas (UNICAMP)  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-1195","authenticated-orcid":false,"given":"C\u00e1ssia R. 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