{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:41:16Z","timestamp":1787013676564,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100024087","name":"Theramex","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024087","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2025,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n Among women with uterine fibroids (UFs), we assess the extent to which the linzagolix effect on pain alleviation is explained by its effect on reducing heavy menstrual bleeding (HMB) and fibroid volume (FV).<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Post hoc analysis on the pooled data from two randomised double\u2010blind placebo\u2010controlled phase 3 trials.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n 94 sites in the US (PRIMROSE 1 trial) and 95 sites in Europe\/US (PRIMROSE 2 trial).<\/jats:p>\n <\/jats:sec>\n \n Population<\/jats:title>\n \n Women aged \u2265\u200918\u2009years with ultrasound\u2010confirmed UFs and HMB (\n n<\/jats:italic>\n \u2009=\u20091012).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Participants were randomised to linzagolix (100\u2009mg and 200\u2009mg, with and without hormonal add\u2010back therapy) versus placebo. A post hoc mediation analysis was conducted on the pooled PRIMROSE 1 and PRIMROSE 2 data. The effect of linzagolix versus placebo on pain reduction was divided into three components (effect explained by HMB reduction associated with linzagolix, FV reduction associated with linzagolix, and remaining [not yet explained] treatment effect), with proportions of each component reported.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measures<\/jats:title>\n The mediation analysis outcome was clinically significant pain reduction, defined as a change of \u2265\u20092 pain categories from baseline to Week 24 using the Numeric Rating Scale (pain categories: no pain (0), and mild (1\u20133), moderate (4\u20136), severe pain (7\u201310)).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the mediation analysis, 28%\u201351% (depending on treatment arm) of linzagolix effect on pain reduction was explained by its effect on HMB reduction, while 2%\u20138% was explained by its effect on FV reduction. The residual proportion ranged between 44% and 67%, depending on treatment arm, and was statistically significant only in the linzagolix 200\u2009mg without add\u2010back therapy arm (\n p<\/jats:italic>\n \u2009=\u20090.002).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This analysis showed that reductions in pain were significantly mediated by reductions in HMB (all doses) and FV (200\u2009mg alone) in linzagolix\u2010treated women with UFs. Further research is needed to identify additional mediating factors.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov<\/jats:ext-link>\n : NCT03070899 and NCT03070951\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1471-0528.18190","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T03:53:51Z","timestamp":1746503631000},"page":"1297-1306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pain Reduction in Linzagolix\u2010Treated Patients With Uterine Fibroids: A Secondary Mediation Analysis of the\n PRIMROSE<\/scp>\n 1 and 2 Phase 3 Trials"],"prefix":"10.1111","volume":"132","author":[{"given":"Sven","family":"Becker","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics University Hospital Frankfurt Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Madeleine","family":"Dolmans","sequence":"additional","affiliation":[{"name":"Gynecology Research Laboratory, Institut de Recherche Exp\u00e9rimentale et Clinique, Department of Gynecology Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Carmona","family":"Herrera","sequence":"additional","affiliation":[{"name":"Gynaecology Department, Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Petraglia","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit, Department of Clinical Experimental and Biomedical Sciences University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan P.","family":"Renner","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg Erlangen Germany"},{"name":"Department of Gynecology and Obstetrics Boeblingen Clinic, Hospital Sindelfingen\u2010B\u00f6blingen B\u00f6blingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca","family":"Ionescu\u2010Ittu","sequence":"additional","affiliation":[{"name":"STATLOG Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"St\u2010Pierre","sequence":"additional","affiliation":[{"name":"STATLOG Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra","family":"Boolell","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs Theramex HQ Ltd London 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