{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:07:07Z","timestamp":1790262427312,"version":"4.1.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Relugolix, an oral GnRH receptor antagonist, is effective in treating uterine myomas and endometriosis. However, concerns persist regarding the venous thromboembolism (VTE) risk associated with its combination with oral estradiol (E2) and norethisterone acetate (NETA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This expert opinion evaluates the thrombotic risk of relugolix combined therapy (relugolix-CT) based on pharmacological data, clinical trials, and regulatory assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A review of pivotal trials (LIBERTY 1, LIBERTY 2, SPIRIT 1, SPIRIT 2), regulatory reports (European Medicines Agency, Food and Drug Administration), and real-world safety data was conducted, focusing on hemostatic effects and VTE risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Relugolix monotherapy reduces estrogen levels, leading to minor decreases in coagulation factors. While E2 and NETA mitigate hypoestrogenic effects, concerns about their prothrombotic potential remain. However, clinical trials and postmarketing surveillance have not shown a significant increase in VTE risk. A meta-analysis suggests that E2-based regimens have a lower thrombotic risk than ethinylestradiol-based therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The VTE risk of relugolix-CT appears lower than that of traditional combined oral contraceptives. Nonetheless, patient selection is essential, particularly for those with thrombotic risk factors. Continued real-world surveillance is crucial to refining its safety profile in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvaf190","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T13:22:57Z","timestamp":1763731377000},"source":"Crossref","is-referenced-by-count":5,"title":["Venous Thromboembolism Risk Associated With Relugolix-estradiol-norethisterone Acetate Combination Therapy"],"prefix":"10.1210","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-5298","authenticated-orcid":false,"given":"Jonathan","family":"Douxfils","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences, Faculty of Medicine, University of Namur , 5000 Namur ,","place":["Belgium"]},{"name":"QUALIblood sa , 4000 Li\u00e8ge ,","place":["Belgium"]},{"name":"Department of Biological Hematology, CHU Clermont-Ferrand, H\u00f4pital Estaing , 63000 Clermont-Ferrand ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Didembourg","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Toxicology Research Unit, Namur Research Institute for Life Sciences, Faculty of Medicine, University of Namur , 5000 Namur ,","place":["Belgium"]},{"name":"QUALIblood sa , 4000 Li\u00e8ge ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Maitrot-Mantelet","sequence":"additional","affiliation":[{"name":"Department of Gynecology Obstetrics II and Reproductive Medicine, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Universitaire Paris Centre, Centre Hospitalier Universitaire Cochin , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Chapron","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Paris , 75014 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,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-4154","authenticated-orcid":false,"given":"Nathalie","family":"Chabbert-Buffet","sequence":"additional","affiliation":[{"name":"Service de Gyn\u00e9cologie, Obst\u00e9trique et M\u00e9decine de la Reproduction, H\u00f4pital Tenon, Sorbonne-Universit\u00e9 , 75970 Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"issue":"7","key":"2026012903163499500_bvaf190-B1","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 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