{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T08:16:25Z","timestamp":1778919385055,"version":"3.51.4"},"reference-count":39,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"am","delay-in-days":378,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007188","name":"Uniformed Services University of the Health Sciences","doi-asserted-by":"publisher","award":["OBG-85-8868"],"award-info":[{"award-number":["OBG-85-8868"]}],"id":[{"id":"10.13039\/100007188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["fertstertscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["F&S Science"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1016\/j.xfss.2022.01.004","type":"journal-article","created":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T11:08:59Z","timestamp":1642244939000},"page":"299-308","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Relugolix and elagolix directly inhibit leiomyoma extracellular matrix production in 2-dimesnional and 3-dimensional cell cultures"],"prefix":"10.1016","volume":"3","author":[{"given":"Danielle","family":"Wright","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-5972","authenticated-orcid":false,"given":"Joy","family":"Britten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minnie","family":"Malik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H.","family":"Catherino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.xfss.2022.01.004_bib1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/AOG.0b013e318183fbab","article-title":"ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas","volume":"112","year":"2008","journal-title":"Obstet Gynecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib2","article-title":"Progestogens or progestogen-releasing intrauterine systems for uterine fibroids","volume":"2","author":"Sangkomkamhang","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.xfss.2022.01.004_bib3","article-title":"Combined hormonal contraceptives for heavy menstrual bleeding","volume":"2","author":"Lethaby","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1016\/j.xfss.2022.01.004_bib4","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1097\/AOG.0b013e3181f20177","article-title":"Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial","volume":"116","author":"Lukes","year":"2010","journal-title":"Obstet Gynecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1479-828X.2001.tb01231.x","article-title":"Ten-year review of hysterectomy morbidity and mortality: can we change direction?","volume":"41","author":"Varol","year":"2001","journal-title":"Aust N Z J Obstet Gynaecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib6","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1016\/j.fertnstert.2020.08.260","article-title":"Relugolix combination therapy significantly reduced menstrual blood loss with first treatment cycle in women with heavy menstrual bleeding associated with uterine fibroids: results for the liberty phase 3 program","volume":"114","author":"Venturella","year":"2020","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib7","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1097\/AOG.0000000000003869","article-title":"Elagolix treatment for up to 12 months in women with heavy menstrual bleeding and uterine leiomyomas","volume":"135","author":"Simon","year":"2020","journal-title":"Obstet Gynecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/GRF.0000000000000171","article-title":"An evidence-based approach to the medical management of fibroids: a systematic review","volume":"59","author":"Bartels","year":"2016","journal-title":"Clin Obstet Gynecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib10","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1056\/NEJMoa2008283","article-title":"Treatment of uterine fibroid symptoms with relugolix combination therapy","volume":"384","author":"Al-Hendy","year":"2021","journal-title":"N Engl J Med"},{"key":"10.1016\/j.xfss.2022.01.004_bib12","doi-asserted-by":"crossref","first-page":"72.e1","DOI":"10.1016\/j.ajog.2020.07.032","article-title":"Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids","volume":"224","author":"Al-Hendy","year":"2021","journal-title":"Am J Obstet Gynecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib13","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.fertnstert.2012.07.1123","article-title":"Gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate and GnRH antagonist cetrorelix acetate directly inhibit leiomyoma extracellular matrix production","volume":"98","author":"Britten","year":"2012","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib14","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1210\/jc.2015-2770","article-title":"Medical castration using the investigational oral GnRH antagonist TAK-385 (relugolix): phase 1 study in healthy males","volume":"100","author":"MacLean","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.xfss.2022.01.004_bib15","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.fertnstert.2006.08.111","article-title":"Novel method to characterize primary cultures of leiomyoma and myometrium with the use of confirmatory biomarker gene arrays","volume":"87","author":"Malik","year":"2007","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib16","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1365-2265.2008.03207.x","article-title":"Retinoic acid treatment of human leiomyoma cells transformed the cell phenotype to one strongly resembling myometrial cells","volume":"69","author":"Malik","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"key":"10.1016\/j.xfss.2022.01.004_bib17","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.fertnstert.2018.07.024","article-title":"Simvastatin, at clinically relevant concentrations, affects human uterine leiomyoma growth and extracellular matrix production","volume":"110","author":"Malik","year":"2018","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib18","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.fertnstert.2012.02.037","article-title":"Development and validation of a three-dimensional in\u00a0vitro model for uterine leiomyoma and patient-matched myometrium","volume":"97","author":"Malik","year":"2012","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib19","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1177\/1933719114545240","article-title":"Leiomyoma cells in 3-dimensional cultures demonstrate an attenuated response to fasudil, a Rho-kinase inhibitor, when compared to 2-dimensional cultures","volume":"21","author":"Malik","year":"2014","journal-title":"Reprod Sci"},{"key":"10.1016\/j.xfss.2022.01.004_bib20","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.fertnstert.2014.03.042","article-title":"Liarozole inhibits transforming growth factor-\u03b23--mediated extracellular matrix formation in human three-dimensional leiomyoma cultures","volume":"102","author":"Levy","year":"2014","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib21","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.fertnstert.2015.12.021","article-title":"Mifepristone inhibits extracellular matrix formation in uterine leiomyoma","volume":"105","author":"Patel","year":"2016","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib22","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.fertnstert.2015.09.006","article-title":"Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones","volume":"105","author":"Malik","year":"2016","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib23","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1177\/1933719118816836","article-title":"Ulipristal acetate mediates decreased proteoglycan expression through regulation of nuclear factor of activated T-cells (NFAT5)","volume":"26","author":"Britten","year":"2019","journal-title":"Reprod Sci"},{"key":"10.1016\/j.xfss.2022.01.004_bib24","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/783289","article-title":"The extracellular matrix contributes to mechanotransduction in uterine fibroids","volume":"2014","author":"Leppert","year":"2014","journal-title":"Obstet Gynecol Int"},{"key":"10.1016\/j.xfss.2022.01.004_bib25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.fertnstert.2006.11.098","article-title":"Human myometrium and leiomyomas express gonadotropin-releasing hormone 2 and gonadotropin-releasing hormone 2 receptor","volume":"88","author":"Parker","year":"2007","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib26","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1210\/en.2004-1384","article-title":"Leiomyoma and myometrial gene expression profiles and their responses to gonadotropin-releasing hormone analog therapy","volume":"146","author":"Luo","year":"2005","journal-title":"Endocrinology"},{"key":"10.1016\/j.xfss.2022.01.004_bib27","first-page":"3215","article-title":"Gonadotropin-releasing hormone (GnRH) and GnRH receptor gene expression in human myometrium and leiomyomata and the direct action of GnRH analogs on myometrial smooth muscle cells and interaction with ovarian steroids in\u00a0vitro","volume":"81","author":"Chegini","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.xfss.2022.01.004_bib28","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/S0006-291X(88)80430-3","article-title":"Gonadotropin-releasing hormone specific binding sites in uterine leiomyomata","volume":"152","author":"Wiznitzer","year":"1988","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.xfss.2022.01.004_bib29","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.fertnstert.2005.06.022","article-title":"Effect of cetrorelix acetate on apoptosis and apoptosis regulatory factors in cultured uterine leiomyoma cells","volume":"84","author":"Kwon","year":"2005","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol Mol Biol Rev"},{"key":"10.1016\/j.xfss.2022.01.004_bib31","doi-asserted-by":"crossref","first-page":"5549","DOI":"10.1210\/jc.2004-0161","volume":"89","author":"Ding","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.xfss.2022.01.004_bib32","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.fertnstert.2017.05.006","article-title":"Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study","volume":"108","author":"Archer","year":"2017","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib33","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1056\/NEJMoa1904351","article-title":"Elagolix for heavy menstrual bleeding in women with uterine fibroids","volume":"382","author":"Schlaff","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1016\/j.xfss.2022.01.004_bib34","doi-asserted-by":"crossref","first-page":"86S","DOI":"10.1097\/01.AOG.0000514919.44544.95","article-title":"Phase 2 study of relugolix vs placebo in heavy menstrual bleeding associated with uterine fibroids [17H]","volume":"129","author":"Hoshiai","year":"2017","journal-title":"Obstet Gynecol"},{"key":"10.1016\/j.xfss.2022.01.004_bib35","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.fertnstert.2019.07.013","article-title":"Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women","volume":"112","author":"Osuga","year":"2019","journal-title":"Fertil Steril"},{"key":"10.1016\/j.xfss.2022.01.004_bib36","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/j.1442-2042.2012.02997.x","article-title":"Gonadotropin-releasing hormone: an update review of the antagonists versus agonists","volume":"19","author":"Van Poppel","year":"2012","journal-title":"Int J Urol"},{"key":"10.1016\/j.xfss.2022.01.004_bib37","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jsps.2016.07.002","article-title":"An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice","volume":"25","author":"Salahudeen","year":"2017","journal-title":"Saudi Pharm J"},{"key":"10.1016\/j.xfss.2022.01.004_bib38","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1177\/1933719116678686","article-title":"Estrogen receptors and signaling in fibroids: role in pathobiology and therapeutic implications","volume":"24","author":"Borahay","year":"2017","journal-title":"Reprod Sci"},{"key":"10.1016\/j.xfss.2022.01.004_bib39","doi-asserted-by":"crossref","first-page":"264","DOI":"10.2119\/2007-00101.YU","article-title":"Differential expression of receptor tyrosine kinases (RTKs) and IGF-I pathway activation in human uterine leiomyomas","volume":"14","author":"Yu","year":"2008","journal-title":"Mol Med"},{"key":"10.1016\/j.xfss.2022.01.004_bib40","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2119\/molmed.2014.00053","article-title":"Signaling pathways in leiomyoma: understanding pathobiology and implications for therapy","volume":"21","author":"Borahay","year":"2015","journal-title":"Mol Med"},{"key":"10.1016\/j.xfss.2022.01.004_bib41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12967-018-1430-x","article-title":"The role of atorvastatin in suppressing tumor growth of uterine fibroids","volume":"16","author":"Shen","year":"2018","journal-title":"J Transl Med"}],"container-title":["F&S Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666335X22000040?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666335X22000040?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T08:05:55Z","timestamp":1778918755000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666335X22000040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["S2666335X22000040"],"URL":"https:\/\/doi.org\/10.1016\/j.xfss.2022.01.004","relation":{},"ISSN":["2666-335X"],"issn-type":[{"value":"2666-335X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Relugolix and elagolix directly inhibit leiomyoma extracellular matrix production in 2-dimesnional and 3-dimensional cell cultures","name":"articletitle","label":"Article Title"},{"value":"F&S Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xfss.2022.01.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc. on behalf of American Society for Reproductive Medicine.","name":"copyright","label":"Copyright"}]}}