title: Clotting factor changes during the first cycle of oral contraceptive use.
abstract: OBJECTIVE
  The risk of venous thromboembolism (VTE) is highest during the initial months of oral contraceptive (OC) use. We sought to evaluate the extent of hemostatic variable changes during the initial OC cycle and if such changes are related to systemic ethinyl estradiol (EE2) exposure.
  
  
  METHODS
  Participants provided multiple blood samples during a 21-day OC cycle (30mcg EE2; 150mcg levonorgestrel) and after a single dose following a washout period. Analytes included D-dimer, factor VIII activity, protein C total antigen and the hepatic proteins corticosteroid-binding globulin (CBG) and sex-hormone-binding globulin (SHBG). EE2 pharmacokinetic analyses related to the 24h after the first OC tablet (OC1) and at steady state (OC21).
  
  
  RESULTS
  Seventeen women completed the study. D-dimer more than doubled by OC6 (p=.013) and remained elevated at OC21 (p=.012). D-dimer levels within women varied widely from day to day. Factor VIII increased 27% by OC2 (p<.001) but declined to a 9% increase by OC21. Protein C increased only 6%. EE2 steady-state area-under-the-curve ranged from 488 to 1103pg∙h/mL; higher levels were not correlated with greater increases in clotting variables. CBG and SHBG increased significantly but were not significantly correlated with levels of EE2 or with the hemostatic variables.
  
  
  CONCLUSIONS
  D-dimer increases during the first OC cycle were at least as great as increases seen with longer OC use. These results provide support for the increased VTE risk during initial OC use. The extreme variability in D-dimer levels may be an important component of this risk.
  
  
  CONCLUSIONS
  This study showed that increases in D-dimer are clearly evident in the first cycle of OC use and may be larger than are seen after a longer duration of use and thus provide biological support for the increased VTE risk during initial OC use found in epidemiological studies.
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA; Department of Epidemiology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: clw3@columbia.edu.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Eisenberger
authors.affiliation: Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Cremers
authors.affiliation: Department of Epidemiology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Lisa V
authors.initials: LV
authors.lastname: Grossman
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
mesh_terms: D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology; D004967:Estrogens / Q000493:pharmacokinetics / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005169:Factor VIII / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology; D010865:Pilot Projects; D011486:Protein C / Q000187:drug effects / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects / Q000378:metabolism; D014156:Transcortin / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
chemical_list: D003280:Contraceptives, Oral, Synthetic; D004967:Estrogens; D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; D012738:Sex Hormone-Binding Globulin; C036309:fibrin fragment D; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D005169:Factor VIII; D014156:Transcortin
keywords: D-dimer; Factor VIII; Oral contraceptives; Protein C; Venous thromboembolism