title: Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study.
abstract: Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18-38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( -0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. -4.4%, p<0.001), activated protein C resistance - normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( -53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( -3.1 vs. -8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this.
authors.affiliation: Université Paris Descartes, Paris, France. pascale.gaussem@egp.aphp.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: Martine
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Thomas
authors.forename: Christilla
authors.initials: C
authors.lastname: Bachelot-Loza
authors.forename: Veronique
authors.initials: V
authors.lastname: Remones
authors.forename: Fouad Dali
authors.initials: FD
authors.lastname: Ali
authors.forename: Martine
authors.initials: M
authors.lastname: Aiach
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
mesh_terms: D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000627:therapeutic use; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage*; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005342:Fibrinolysis; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage*; D008535:Megestrol / Q000008:administration & dosage*; D009649:Norpregnadienes / Q000008:administration & dosage*; D010919:Placebos; D013927:Thrombosis; D016896:Treatment Outcome
chemical_list: D003277:Contraceptives, Oral, Combined; D009649:Norpregnadienes; D010919:Placebos; D004997:Ethinyl Estradiol; D004958:Estradiol; D016912:Levonorgestrel; C038501:nomegestrol acetate; D008535:Megestrol