title: Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral contraceptives.
abstract: BACKGROUND
  Oral contraceptives (OC) increase the risk of venous thromboembolism that depends on the OC formulation and could at least partially be explained by impaired function of the protein C-system (APC resistance) and the tissue factor pathway inhibitor (TFPI)-system. There is limited information available on the effects of OC, containing a newer progestogen- drospirenone (DRSP-OC) on these two major anticoagulant pathways, thrombin generation, reflecting the overall state of coagulation, and other coagulation parameters.
  
  
  METHODS
  In a study population consisting of 14 healthy women (age 21-33 years) we investigated the effect of the menstrual cycle and subsequent use of DRSP-OC on APC resistance, the function of the TFPI-system, thrombin generation and on their major determinants, i.e. prothrombin, antithrombin, FV, FX, FVIII, protein C, protein S(total and free) and TFPI(full-length and free).
  
  
  RESULTS
  All studied parameters remained unchanged during the menstrual cycle. During DRSP-OC use we observed a significant increase in APC resistance (~2.4-fold), thrombin generation measured at low (~2.2-fold) and high tissue factor concentrations (~1.4-fold), plasma concentrations of prothrombin (19%), FX (31%), FVIII (17%) and protein C (43%). DRSP-OC use impaired the function of the TFPI-system and decreased plasma levels of antithrombin (-6%), FV (-22%), protein Stotal (-21%), protein Sfree (-20%), TFPIfull-length (-36%) and TFPIfree (-46%).
  
  
  CONCLUSIONS
  DRSP-OC caused procoagulant changes in all studied haemostatic parameters. The impairment of the protein C- and TFPI-systems was more pronounced than the impairment of the coagulation pathways and can at least partially account for the increased risk of venous thromboembolism in users of DRSP-OC.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; University Women´s Hospital, Otto-von-Guericke University, Magdeburg, Germany. Electronic address: svetlana.tchaikovski@med.ovgu.de.
authors.forename: S N
authors.initials: SN
authors.lastname: Tchaikovski
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: M C L G D
authors.initials: MC
authors.lastname: Thomassen
authors.affiliation: University Women´s Hospital, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: S D
authors.initials: SD
authors.lastname: Costa
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Bremme
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Rosing
mesh_terms: D000328:Adult; D000736:Androstenes / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D003276:Contraceptives, Oral / Q000494:pharmacology*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008597:Menstrual Cycle; D017293:Protein S / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D055815:Young Adult
chemical_list: D000736:Androstenes; D003276:Contraceptives, Oral; D008074:Lipoproteins; D017293:Protein S; C051928:lipoprotein-associated coagulation inhibitor; D013917:Thrombin; C035144:drospirenone
keywords: Drospirenone-containing oral contraceptives; Protein S; TFPI; Tthrombin generation