title: Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.
abstract: BACKGROUND
  A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance.
  
  
  OBJECTIVE
  The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel.
  
  
  METHODS
  Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2 mg/dienogest 2 mg, 17 days estradiol valerate 2 mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three.
  
  
  RESULTS
  Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel.
  
  
  CONCLUSIONS
  The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.
authors.affiliation: Dinox BV, Groningen, the Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Klipping
authors.forename: Ingrid
authors.initials: I
authors.lastname: Duijkers
authors.forename: Susanne
authors.initials: S
authors.lastname: Parke
authors.forename: Uwe
authors.initials: U
authors.lastname: Mellinger
authors.forename: Marco
authors.initials: M
authors.lastname: Serrani
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Junge
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood; D000293:Adolescent; D000328:Adult; D000941:Antigens / Q000187:drug effects / Q000378:metabolism; D000990:Antithrombin III / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005167:Factor VII / Q000187:drug effects / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D009277:Nandrolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D010349:Patient Compliance / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000097:blood; D011486:Protein C / Q000378:metabolism; D011498:Protein Precursors / Q000097:blood; D017293:Protein S / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D055815:Young Adult
chemical_list: D000941:Antigens; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D011486:Protein C; D011498:Protein Precursors; D017293:Protein S; D012738:Sex Hormone-Binding Globulin; C042580:factor VII clotting antigen; C036309:fibrin fragment D; D004997:Ethinyl Estradiol; C023635:dienogest; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D000990:Antithrombin III; D005167:Factor VII; D011516:Prothrombin; D005169:Factor VIII; D005340:Fibrinogen