{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:24:01Z","timestamp":1792873441306,"version":"4.5.0"},"reference-count":114,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Combined oral contraceptives (COCs) remain one of the most popular reversible contraceptive methods worldwide. Still, regardless of the drug composition and duration of therapy, almost all COCs are associated with the risk of venous thrombosis. This review highlights the main pathogenetic mechanisms of thrombosis development during oral contraceptive use. Increase the production of certain clotting factors; a decrease in antithrombin and protein S levels; acquired resistance to activated protein C; a reduction in tissue factor pathway inhibitor (TFPI); indirect endothelial activation; inhibition of endogenous fibrinolysis; regulation of tissue factor by estradiol-sensitive microRNA; homocysteine imbalance caused by decreased intestinal reabsorption of folates and vitamin B-12; reduced bioavailability of nitric oxide (NO) due to high homocysteine levels; higher blood pressure, water retention, insulin resistance, increased levels of pro-inflammatory C-reactive protein (CRP) and uric acid, and antifibrinolytic (plasminogen activator inhibitor 1 type, PAI-1) biomarkers as consequences of NO deficiency; increased platelet adhesiveness and ADP-induced aggregation, which promote fibrinogen binding; and increased expression of pro-inflammatory cytokines are the main thrombotic effects of COCs use. Clinicians should carefully evaluate each patient\u2019s individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications.<\/jats:p>","DOI":"10.3390\/ijms262211010","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T09:06:36Z","timestamp":1763111196000},"page":"11010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Combined Oral Contraceptives and the Risk of Thrombosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0725-9686","authenticated-orcid":false,"given":"Jamilya","family":"Khizroeva","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Bitsadze","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Sukhikh","sequence":"additional","affiliation":[{"name":"FSBI \u00abNational Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov\u00bb, Ministry of Health of the Russian Federation, 4, Oparina Street, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tretyakova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-9910","authenticated-orcid":false,"given":"Jean-Christophe","family":"Gris","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia"},{"name":"Faculty of Pharmaceutical and Biological Sciences, Montpellier University, 34093 Montpellier, France"},{"name":"Department of Hematology, CHU N\u00eemes, Montpellier University, 30029 N\u00eemes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Elalamy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia"},{"name":"Hematology Department, Facult\u00e9 Privee de M\u00e9decine de Marrakech (FPMM), Route Amizmiz, Marrakech 42312, Morocco"},{"name":"Hopital Americain de Paris, 55 rue du Ch\u00e2tea, 92200 Neuilly-Sur-Seine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2316-6348","authenticated-orcid":false,"given":"Grigoris","family":"Gerotziafas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia"},{"name":"Sorbonne University, INSERM UMRS-938, Team \u201cCancer Vessels, Biology and Therapeutics\u201d, Group \u201cCancer-Hemostasis-Angiogenesis\u201d, Institut Universitaire de Canc\u00e9rologie, Consultation Thrombosis in Oncology (COTHON), Tenon-Saint Antoine Hospital, AP-HP, 75020 Paris, France"},{"name":"Thrombosis Center, Tenon\u2014Saint Antoine University Hospital, H\u00f4pitaux Universitaires Est Parisien, Assitance Publique H\u00f4pitaix de Paris (AP-HP), 4 Rue de la Chine, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daredzhan","family":"Kapanadze","sequence":"additional","affiliation":[{"name":"Center of Pathology of Pregnancy and Hemostasis \u00abMedlabi\u00bb, 340112 Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Kvaratskheliia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Perinatal Medicine, The I.M. 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