{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:17:58Z","timestamp":1790115478722,"version":"4.0.1"},"reference-count":63,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018142","name":"Fuji Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Appl Thromb Hemost"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Venous thromboembolism is a serious safety concern in women using combined oral contraceptives; ethinyl estradiol (EE) is widely used as an estrogen. Estetrol (E4) is a native estrogen with selective tissue activity and exclusively produced by the fetal liver. This study used a multicenter, randomized, open-label, active-controlled, parallel-group design to evaluate the effects of E4 combined with drospirenone (DRSP) on coagulation and fibrinolysis in Japanese patients with endometriosis. Participants were randomized to receive either E4 15\u2005mg\/DRSP 3\u2005mg or EE 20\u2005\u00b5g\/DRSP 3\u2005mg for 12 weeks. E4\/DRSP and EE\/DRSP were administered orally once a day in a cyclic regimen, ie, 24-day active use followed by a 4-day hormone-free period, and a flexible extended regimen, respectively, and blood coagulation and fibrinolysis markers were measured. The effect on coagulation and fibrinolysis was considerably less in the E4\/DRSP group than in the EE\/DRSP group. Major anticoagulant proteins, protein S (free, total) and tissue factor pathway inhibitor (free), were reduced following EE\/DRSP treatment. Consequently, thrombin generation determined by the activated protein C sensitivity ratio was increased by approximately 4-fold in the EE\/DRSP group than in the E4\/DRSP group. Eventually, the fibrinolysis cascade was triggered to compensate for disturbed coagulation, and D-dimer levels were 4.7-fold higher in the EE\/DRSP group than in the E4\/DRSP group. This study demonstrated that the effect of E4\/DRSP on the blood coagulation and fibrinolysis cascades was significantly less than that of EE\/DRSP in participants with endometriosis, a disease of women of advanced and reproductive age (jRCT2080225090, https:\/\/jrct.niph.go.jp\/en-latest-detail\/jRCT2080225090 ).<\/jats:p>","DOI":"10.1177\/10760296241286514","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T04:31:02Z","timestamp":1727411462000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["Impact of Estetrol Combined with Drospirenone on Blood Coagulation and Fibrinolysis in Patients with Endometriosis: A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel-Group Study"],"prefix":"10.1177","volume":"30","author":[{"given":"Takao","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hamamatsu Medical Center, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6217-167X","authenticated-orcid":false,"given":"Masashi","family":"Hirayama","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Fuji Pharma Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Nogami","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Fuji Pharma Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanna","family":"Meguro","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Fuji Pharma Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Iiduka","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Fuji Pharma Co., Ltd, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Foidart","sequence":"additional","affiliation":[{"name":"Estetra SRL, Mithra Pharmaceuticals, Li\u00e8ge, Belgium"},{"name":"Department of Obstetrics and Gynecology, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Douxfils","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pharmacy, Namur Research Institute for Life Sciences (NARILIS), Clinical Pharmacology Research Group, University of Namur, Namur, Belgium"},{"name":"Research Department, Qualiblood sa, Namur, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasuku","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, 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