{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:25:00Z","timestamp":1792686300520,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ObsEva","award":["5\/4\/150\/5"],"award-info":[{"award-number":["5\/4\/150\/5"]}]},{"DOI":"10.13039\/501100024087","name":"Theramex","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016288","name":"Kissei","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gedeon Richter and Theramex"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Does linzagolix administered orally once daily for up to 3\u2009months at a dose of 75\u2009mg alone or 200\u2009mg in combination with add-back therapy (ABT) (1.0\u2009mg estradiol; 0.5\u2009mg norethindrone acetate, also known as norethisterone acetate [NETA]) demonstrate better efficacy than placebo in the management of endometriosis-related dysmenorrhea and non-menstrual pelvic pain?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Combining 200\u2009mg linzagolix with ABT was found to significantly reduce dysmenorrhea and non-menstrual pelvic pain at 3\u2009months of therapy, while a daily dose of 75\u2009mg linzagolix yielded a significant decrease only in dysmenorrhea at 3\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY?<\/jats:title>\n                    <jats:p>A previously published Phase 2, dose-finding study reported that at a dose of 200\u2009mg daily, linzagolix promotes full suppression of estradiol secretion to serum levels below 20\u2009pg\/ml and noted that the addition of ABT may be needed to manage hypoestrogenic side effects. At lower doses (75\u2009mg and 100\u2009mg\/day), linzagolix maintains estradiol values within the target range of 20\u201360\u2009pg\/ml, which could be ideal to alleviate symptoms linked to endometriosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>EDELWEISS 3 was a multicenter, prospective, randomized, placebo-controlled, double-blind, double-dummy Phase 3 study to evaluate the safety and efficacy of linzagolix for the treatment of moderate-to-severe endometriosis-associated pain. Treatment was administered orally once daily for up to 6\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>In the EDELWEISS 3 trial, 486 subjects with moderate-to-severe endometriosis-associated pain were randomized at a 1:1:1 ratio to one of the three study groups: placebo, 75\u2009mg linzagolix alone or 200\u2009mg linzagolix in association with ABT. Pain was measured daily on a verbal rating scale and recorded in an electronic diary.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>At 3\u2009months, the daily 200\u2009mg linzagolix dose with ABT met the primary efficacy objective, showing clinically meaningful and statistically significant reductions in dysmenorrhea and non-menstrual pelvic pain, with stable or decreased use of analgesics. The proportion of responders for dysmenorrhea in the 200\u2009mg linzagolix with ABT group was 72.9% compared with 23.5% in the placebo group (P\u2009&amp;lt;\u20090.001), while the rates of responders for non-menstrual pelvic pain were 47.3% and 30.9% (P\u2009=\u20090.007), respectively. The 75\u2009mg linzagolix daily dose demonstrated a clinically meaningful and statistically significant reduction in dysmenorrhea versus placebo at 3\u2009months. The proportion of responders for dysmenorrhea in the 75\u2009mg linzagolix group was 44.0% compared with 23.5% in the placebo group (P\u2009&amp;lt;\u20090.001). Although the 75\u2009mg dose showed a trend toward reduction in non-menstrual pelvic pain at 3\u2009months relative to the placebo, it was not statistically significant (P\u2009=\u20090.279). Significant improvements in dyschezia and overall pelvic pain were observed in both linzagolix groups when compared to placebo. Small improvements in dyspareunia scores were observed in both linzagolix groups but they were not significant. In both groups, hypoestrogenic effects were mild, with low rates of hot flushes and bone density loss of &amp;lt;1%. A daily dose of 200\u2009mg linzagolix with ABT or 75\u2009mg linzagolix alone was found to significantly reduce dysmenorrhea and non-menstrual pelvic pain also at 6\u2009months of therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>Efficacy was compared between linzagolix groups and placebo; however, it would be useful to have results from comparative studies with estro-progestogens or progestogens. It will be important to ascertain whether gonadotropin-releasing hormone antagonists have significant benefits over traditional first-line medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Linzagolix administered orally once daily at a dose of 200\u2009mg in combination with add-back therapy (ABT) demonstrated better efficacy and safety than placebo in the management of moderate-to-severe endometriosis-associated pain. The quality of life was improved and the risks of bone loss and vasomotor symptoms were minimized due to the ABT. The 75\u2009mg dose alone could be suitable for chronic treatment of endometriosis-associated pain without the need for concomitant hormonal ABT, but further research is needed to confirm this. If confirmed, it would offer a viable option for women who do not want to wish to have ABT or for whom it is contraindicated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>Funding for the EDELWEISS 3 study was provided by ObsEva (Geneva, Switzerland). Analysis of data and manuscript writing were partially supported by ObsEva (Geneva, Switzerland), Theramex (London, UK) and Kissei (Japan) and grant 5\/4\/150\/5 was awarded to M.-M.D. by FNRS. J.D. was a member of the scientific advisory board of ObsEva until August 2022, a member of the scientific advisory board of PregLem, and received personal fees from Gedeon Richter, ObsEva and Theramex. J.D. received consulting fees, speakers\u2019 fees, and travel support from Gedeon Richter, Obseva and Theramex, which was paid to their institution. C.B. has received fees from Theramex, Gedeon Richter, and Myovant, and travel support from Gedeon Richter\u2014all funds went to the University of Oxford. He was a member of the data monitoring board supervising the current study, and served at an advisory board for endometriosis studies of Myovant. H.T. has received grants from Abbvie and was past president of ASRM. F.C.H. has received fees from Gedeon Richter and Theramex. O.D. received fees for lectures from Gedeon Richter and ObsEva and research grants for clinical studies from Preglem and ObsEva independent from the current study. A.H. has received grants from NIHR, UKRI, CSO, Wellbeing of Women, and Roche Diagnostics; he has received fees from Theramex. A.H.\u2019s institution has received honoraria for consultancy from Roche Diagnostics, Gesynta, and Joii. M.P. has nothing to declare. F.P. has received fees from Theramex. S.P.R. has been a member of the scientific advisory board of Gedeon Richter and received fees from Gedeon Richter. A.P. and M.B. are employees of Theramex. E.B. was an employee of ObsEva, sponsor chair of the data monitoring board supervising the current study, and has been working as a consultant for Theramex since December 2022; she owns stock options in ObsEva. M.-M.D. has received fees and travel support from Gedeon Richter and Theramex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>NCT 03992846.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION DATE<\/jats:title>\n                    <jats:p>20 June 2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATE OF FIRST PATIENT\u2019S ENROLLMENT<\/jats:title>\n                    <jats:p>13 June 2019.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deae076","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T12:42:17Z","timestamp":1712148137000},"page":"1208-1221","source":"Crossref","is-referenced-by-count":52,"title":["Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3)"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2528-206X","authenticated-orcid":false,"given":"Jacques","family":"Donnez","sequence":"first","affiliation":[{"name":"Department of Gynecology, Universit\u00e9 Catholique de Louvain , Brussels, Belgium"},{"name":"Department of Gynecology, Soci\u00e9t\u00e9 de Recherche pour l\u2019Infertilit\u00e9 (SRI) , Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9870-9581","authenticated-orcid":false,"given":"Christian","family":"Becker","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s & Reproductive Health, Endometriosis CaRe Centre, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1720-8310","authenticated-orcid":false,"given":"Hugh","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive sciences, Yale School of Medicine , New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Carmona Herrera","sequence":"additional","affiliation":[{"name":"Gynaecology Department, Clinic Institute of Gynaecology, Obstetrics and Neonatology (ICGON), Hospital Clinic of Barcelona, Universitat de Barcelona , Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Donnez","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Gyn\u00e9cologie, Centre de l\u2019Endom\u00e9triose Complexe, Chirurgie endoscopique pelvienne, Polyclinique Urbain V (ELSAN Group) , Avignon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9656-493X","authenticated-orcid":false,"given":"Andrew","family":"Horne","sequence":"additional","affiliation":[{"name":"Department of Gynecology, EXPPECT and MRC Centre for Reproductive Health, University of Edinburgh , Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Paszkowski","sequence":"additional","affiliation":[{"name":"Third Chair and Department of Gynecology, Medical University of Lublin , Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-625X","authenticated-orcid":false,"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, Hospital B\u00f6blingen, Klinikverbund-Suedwest , Sindelfingen 71065, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amisha","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Theramex UK Ltd , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra","family":"Boolell","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Theramex UK Ltd , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Bestel","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Theramex UK Ltd , London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6331-3026","authenticated-orcid":false,"given":"Marie-Madeleine","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"},{"name":"Gynecology Department, Cliniques Universitaires St-Luc , Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"2024060305590077500_deae076-B1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1055\/s-0036-1597123","article-title":"Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction","volume":"35","author":"Aredo","year":"2017","journal-title":"Semin Reprod Med"},{"key":"2024060305590077500_deae076-B2","doi-asserted-by":"crossref","first-page":"729601","DOI":"10.3389\/fgwh.2021.729601","article-title":"Medical treatment for endometriosis: tolerability, quality of life and adherence","volume":"2","author":"Barbara","year":"2021","journal-title":"Front Glob Womens Health"},{"key":"2024060305590077500_deae076-B3","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/0002-9378(92)91706-G","article-title":"Hormone treatment of endometriosis: the estrogen threshold hypothesis","volume":"166","author":"Barbieri","year":"1992","journal-title":"Am J Obstet Gynecol"},{"key":"2024060305590077500_deae076-B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hropen\/hoac009","article-title":"ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis","volume":"2022","author":"Becker","year":"2022","journal-title":". Hum Reprod Open"},{"key":"2024060305590077500_deae076-B5","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0002-9378(81)90478-6","article-title":"Dosage aspects of danazol therapy in endometriosis: short-term and long-term effectiveness","volume":"139","author":"Biberoglu","year":"1981","journal-title":"Am J Obstet Gynecol"},{"key":"2024060305590077500_deae076-B6","doi-asserted-by":"crossref","first-page":"1020827","DOI":"10.3389\/fendo.2022.1020827","article-title":"Endometriosis-associated infertility: from pathophysiology to tailored treatment","volume":"13","author":"Bonavina","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2024060305590077500_deae076-B7","doi-asserted-by":"crossref","first-page":"693","DOI":"10.2217\/whe.15.56","article-title":"Recurrence of endometriosis: risk factors, mechanisms and bio-markers","volume":"11","author":"Bozdag","year":"2015","journal-title":"Womens Health (Lond)"},{"key":"2024060305590077500_deae076-B8","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.fertnstert.2023.03.006","article-title":"Endometriosis and adenomyosis: shared pathophysiology","volume":"119","author":"Bulun","year":"2023","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B9","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1210\/er.2018-00242","article-title":"Endometriosis","volume":"40","author":"Bulun","year":"2019","journal-title":"Endocr Rev"},{"key":"2024060305590077500_deae076-B10","doi-asserted-by":"crossref","first-page":"7138","DOI":"10.3390\/ijms22137138","article-title":"Can endometriosis-related oxidative stress pave the way for new treatment targets?","volume":"22","author":"Cacciottola","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2024060305590077500_deae076-B11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.rbmo.2020.09.018","article-title":"Long-term hormonal treatment reduces repetitive surgery for endometriosis recurrence","volume":"42","author":"Capezzuoli","year":"2021","journal-title":"Reprod Biomed Online"},{"key":"2024060305590077500_deae076-B12","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.fertnstert.2017.01.003","article-title":"Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills","volume":"107","author":"Casper","year":"2017","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B13","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1093\/humrep\/deab151","article-title":"The heterogeneity of endometriotic lesions could be explained by their progesterone resistance","volume":"36","author":"Donnez","year":"2021","journal-title":"Hum Reprod"},{"key":"2024060305590077500_deae076-B14","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.3390\/ijms23031518","article-title":"Endometriosis: an inflammatory disease that requires new therapeutic options","volume":"23","author":"Donnez","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2024060305590077500_deae076-B15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/humupd\/8.1.89","article-title":"The efficacy of medical and surgical treatment of endometriosis-associated infertility: arguments in favour of a medico-surgical approach","volume":"8","author":"Donnez","year":"2002","journal-title":"Hum Reprod Update"},{"key":"2024060305590077500_deae076-B16","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3390\/jcm10051085","article-title":"Endometriosis and medical therapy: from progestogens to progesterone resistance to GnRH antagonists: a review","volume":"10","author":"Donnez","year":"2021","journal-title":"J Clin Med"},{"key":"2024060305590077500_deae076-B17","doi-asserted-by":"crossref","first-page":"11342","DOI":"10.3390\/ijms222111342","article-title":"GnRH antagonists with or without add-back therapy: a new alternative in the management of endometriosis?","volume":"22","author":"Donnez","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2024060305590077500_deae076-B18","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2147\/DDDT.S269976","article-title":"Profile of linzagolix in the management of endometriosis, including design, development and potential place in therapy: a narrative review","volume":"17","author":"Donnez","year":"2023","journal-title":"Drug Des Devel Ther"},{"key":"2024060305590077500_deae076-B19","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(22)01475-1","article-title":"Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials","volume":"400","author":"Donnez","year":"2022","journal-title":"Lancet"},{"key":"2024060305590077500_deae076-B20","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.fertnstert.2017.01.013","article-title":"Partial suppression of estradiol: a new strategy in endometriosis management?","volume":"107","author":"Donnez","year":"2017","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B21","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.fertnstert.2020.02.114","article-title":"Treatment of endometriosis-associated pain with linzagolix, an oral gonadotropin-releasing hormone-antagonist: a randomized clinical trial","volume":"114","author":"Donnez","year":"2020","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B22","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/humrep\/det457","article-title":"ESHRE guideline: management of women with endometriosis","volume":"29","author":"Dunselman","year":"2014","journal-title":"Hum Reprod"},{"key":"2024060305590077500_deae076-B23","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.1210\/jc.2018-01227","article-title":"Progesterone receptor status predicts response to progestin therapy in endometriosis","volume":"103","author":"Flores","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2024060305590077500_deae076-B24","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.fertnstert.2006.06.015","article-title":"Economic burden of endometriosis","volume":"86","author":"Gao","year":"2006","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B25","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1016\/S0140-6736(22)00622-5","article-title":"Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2)","volume":"399","author":"Giudice","year":"2022","journal-title":"Lancet"},{"key":"2024060305590077500_deae076-B26","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","article-title":"Endometriosis","volume":"364","author":"Giudice","year":"2004","journal-title":"Lancet"},{"key":"2024060305590077500_deae076-B27","doi-asserted-by":"crossref","first-page":"e070750","DOI":"10.1136\/bmj-2022-070750","article-title":"Pathophysiology, diagnosis, and management of endometriosis","volume":"379","author":"Horne","year":"2022","journal-title":"BMJ"},{"key":"2024060305590077500_deae076-B28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2741\/e358","article-title":"Peritoneal endometriosis is an inflammatory disease","volume":"E4","author":"Lousse","year":"2012","journal-title":"Front Biosci"},{"key":"2024060305590077500_deae076-B29","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1210\/jc.2016-3845","article-title":"Dose-dependent suppression of gonadotrophins and ovarian hormones by elagolix in healthy premenopausal women","volume":"102","author":"Ng","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2024060305590077500_deae076-B30","author":"NICE guideline [NG73]","year":"2017"},{"key":"2024060305590077500_deae076-B31","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0015-0282(97)00191-X","article-title":"Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities","volume":"68","author":"Nisolle","year":"1997","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B32","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMct0803719","article-title":"Gonadotropin-releasing hormone agonists for endometriosis","volume":"359","author":"Olive","year":"2008","journal-title":"N Engl J Med"},{"key":"2024060305590077500_deae076-B33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1177\/2284026520933141","article-title":"The frequency of endometriosis in the general and selected populations: a systematic review","volume":"12","author":"Parazzini","year":"2020","journal-title":"J Endometri Pelvic Pain Disord"},{"key":"2024060305590077500_deae076-B34","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bpobgyn.2018.01.006","article-title":"Pathogenesis of endometriosis: interaction between endocrine and in\ufb02ammatory pathways","volume":"50","author":"Patel","year":"2018","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2024060305590077500_deae076-B35","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/humupd\/dmw031","article-title":"Sexual function in endometriosis patients and their partners: effect of the disease and consequences of treatment","volume":"22","author":"Pluchino","year":"2016","journal-title":"Hum Reprod Update"},{"key":"2024060305590077500_deae076-B36","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1111\/bcp.15171","article-title":"A model-based analysis to guide gonadotropin-releasing hormone receptor antagonist use for management of endometriosis","volume":"88","author":"Pohl","year":"2022","journal-title":"Br J Clin Pharmacol"},{"key":"2024060305590077500_deae076-B37","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1007\/s43032-020-00172-z","article-title":"Effects of combined GnRH receptor antagonist linzagolix and hormonal add-back therapy on vaginal bleeding-delayed add-back onset does not improve bleeding pattern","volume":"27","author":"Pohl","year":"2020","journal-title":"Reprod Sci"},{"key":"2024060305590077500_deae076-B38","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.fertnstert.2014.02.012","article-title":"Treatment of pelvic pain associated with endometriosis: a committee opinion","volume":"101","author":"Practice Committee of the American Society for Reproductive Medicine","year":"2014","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B39","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/humupd\/dmaa009","article-title":"Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure","volume":"26","author":"Reis","year":"2020","journal-title":"Hum Reprod Update"},{"key":"2024060305590077500_deae076-B40","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/humrep\/des073","article-title":"The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres","volume":"27","author":"Simoens","year":"2012","journal-title":"Hum Reprod"},{"key":"2024060305590077500_deae076-B41","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s12325-018-0667-3","article-title":"Real-world evaluation of direct and indirect economic burden among endometriosis patients in the United States","volume":"35","author":"Soliman","year":"2018","journal-title":"Adv Ther"},{"key":"2024060305590077500_deae076-B42","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.fertnstert.2017.03.020","article-title":"Incremental direct and indirect cost burden attributed to endometriosis surgeries in the United States","volume":"107","author":"Soliman","year":"2017","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B43","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/humrep\/dev335","article-title":"The direct and indirect costs associated with endometriosis: a systematic literature review","volume":"31","author":"Soliman","year":"2016","journal-title":"Hum Reprod"},{"key":"2024060305590077500_deae076-B44","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/AOG.0000000000002675","article-title":"Long-term outcomes of elagolix in women with endometriosis: results from two extension studies","volume":"132","author":"Surrey","year":"2018","journal-title":"Obstet Gynecol"},{"key":"2024060305590077500_deae076-B45","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1056\/NEJMoa1700089","article-title":"Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist","volume":"377","author":"Taylor","year":"2017","journal-title":"N Engl J Med"},{"key":"2024060305590077500_deae076-B46","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis is a chronic systemic disease: clinical challenges and novel innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet"},{"key":"2024060305590077500_deae076-B47","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/1440-1681.13688","article-title":"Pharmacological characterization of linzagolix, a novel, orally active, non-peptide antagonist of gonadotropin-releasing hormone receptors","volume":"49","author":"Tezuka","year":"2022","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2024060305590077500_deae076-B48","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11154-021-09666-w","article-title":"Hormonal treatments for endometriosis: the endocrine background","volume":"23","author":"Vannuccini","year":"2022","journal-title":"Rev Endocr Metab Disord"},{"key":"2024060305590077500_deae076-B49","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.fertnstert.2016.10.022","article-title":"Estrogen-progestins and progestins for the management of endometriosis","volume":"106","author":"Vercellini","year":"2016","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B50","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bpobgyn.2018.01.015","article-title":"Medical treatment of endometriosis-related pain","volume":"51","author":"Vercellini","year":"2018","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2024060305590077500_deae076-B51","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.fertnstert.2018.01.037","article-title":"A stepped-care approach to symptomatic endometriosis management: a participatory research initiative","volume":"109","author":"Vercellini","year":"2018","journal-title":"Fertil Steril"},{"key":"2024060305590077500_deae076-B52","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/humrep\/dey368","article-title":"Elagolix for endometriosis: all that glitters is not gold","volume":"34","author":"Vercellini","year":"2019","journal-title":"Hum Reprod"},{"key":"2024060305590077500_deae076-B53","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/humupd\/dmz005","article-title":"Endometriosis and nuclear receptors","volume":"25","author":"Yilmaz","year":"2019","journal-title":"Hum Reprod Update"},{"key":"2024060305590077500_deae076-B54","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N Engl J Med"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/39\/6\/1208\/58039905\/deae076.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/39\/6\/1208\/58039905\/deae076.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T10:49:51Z","timestamp":1717411791000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/39\/6\/1208\/7656387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,4,22]]},"published-print":{"date-parts":[[2024,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deae076","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,6,1]]},"published":{"date-parts":[[2024,4,22]]}}}