Clotting factor changes during the first cycle of oral contraceptive use Journal Article


Authors: Westhoff, C. L.; Eisenberger, A.; Tang, R.; Cremers, S.; Grossman, L. V.; Pike, M. C.
Article Title: Clotting factor changes during the first cycle of oral contraceptive use
Abstract: Objectives 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. Study design Participants provided multiple blood samples during a 21-day OC cycle (30 mcg EE2; 150 mcg 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 24 h 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 1103 pg·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. Implications 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. © 2016 Published by Elsevier Inc.
Keywords: adult; protein blood level; steady state; sex hormone binding globulin; venous thromboembolism; d dimer; blood clotting factor 8; factor viii; levonorgestrel; oral contraceptives; protein c; d-dimer; blood clotting factor; ethinylestradiol; human; female; article; oral contraceptive use; transcortin
Journal Title: Contraception
Volume: 93
Issue: 1
ISSN: 0010-7824
Publisher: Elsevier Inc.  
Date Published: 2016-01-01
Start Page: 70
End Page: 76
Language: English
DOI: 10.1016/j.contraception.2015.09.015
PROVIDER: scopus
PUBMED: 26452328
PMCID: PMC5004596
DOI/URL:
Notes: Article -- Export Date: 3 February 2016 -- Source: Scopus
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MSK Authors
  1. Malcolm Pike
    141 Pike