Combined Oral Contraceptives and the Risk of Thrombosis.

Jamilya Khizroeva, Victoria Bitsadze, Gennady Sukhikh, Maria Tretyakova, Jean-Christophe Gris, Ismail Elalamy, Grigoris Gerotziafas, Daredzhan Kapanadze, Margaret Kvaratskheliia, Alena Tatarintseva, Azaliia Khisamieva, Ivan Hovancev, Fidan Yakubova, Alexander Makatsariya

Journal: International journal of molecular sciences 2025;26(22):

PMID: 41303494

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Abstract

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's individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications.

Address: 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.; FSBI «National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I.Kulakov», Ministry of Health of the Russian Federation, 4, Oparina Street, 117997 Moscow, Russia.; 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.; Faculty of Pharmaceutical and Biological Sciences, Montpellier University, 34093 Montpellier, France.; Department of Hematology, CHU Nîmes, Montpellier University, 30029 Nîmes, France.; 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.; Hematology Department, Faculté Privee de Médecine de Marrakech (FPMM), Route Amizmiz, Marrakech 42312, Morocco.; Hopital Americain de Paris, 55 rue du Châtea, 92200 Neuilly-Sur-Seine, France.; 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.; Sorbonne University, INSERM UMRS-938, Team "Cancer Vessels, Biology and Therapeutics", Group "Cancer-Hemostasis-Angiogenesis", Institut Universitaire de Cancérologie, Consultation Thrombosis in Oncology (COTHON), Tenon-Saint Antoine Hospital, AP-HP, 75020 Paris, France.; Thrombosis Center, Tenon-Saint Antoine University Hospital, Hôpitaux Universitaires Est Parisien, Assitance Publique Hôpitaix de Paris (AP-HP), 4 Rue de la Chine, 75020 Paris, France.; Center of Pathology of Pregnancy and Hemostasis «Medlabi», 340112 Tbilisi, Georgia.

DOI: 10.3390/ijms262211010

MeSH Terms: Humans, Contraceptives, Oral, Combined, Thrombosis, Female, Risk Factors, Fibrinolysis, Biomarkers