title: Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial.
abstract: BACKGROUND
  The use of combined oral contraceptives is associated with a 3- to 6-fold increased risk of venous thrombosis. This increased risk depends on the estrogen dose as well as the progestogen type of combined oral contraceptives. Thrombin generation-based activated protein C resistance (APC resistance) and sex hormone-binding globulin (SHBG) levels predict the thrombotic risk of a combined hormonal contraceptive. Recently, a four-phasic oral contraceptive containing dienogest (DNG) and estradiol valerate (E2V) has been marketed. The aim of this study was to evaluate the thrombotic risk of the DNG/E2V oral contraceptive by comparing APC resistance by measuring normalized APC sensitivity ratios (nAPCsr) and SHBG levels in users of oral contraceptives containing dienogest and estradiol valerate (DNG/E2V) and oral contraceptives containing levonorgestrel and ethinyl estradiol (LNG/EE).
  
  
  METHODS
  We conducted a single-center, randomized, open label, parallel-group study in 74 women using DNG/E2V or LNG/EE, and measured nAPCsr and SHBG levels in every phase of the regimen of DNG/E2V.
  
  
  RESULTS
  During the pill cycle SHBG levels did not differ between DNG/E2V users and LNG/EE users. nAPCsr levels were overall slightly lower in DNG/E2V users than in LNG/EE users, mean difference -0.44 (95% CI, -1.04 to 0.17) for day 2, -0.20 (95% CI, -0.76 to 0.37) for day 7, -0.27 (95% CI, -0.81 to 0.28) for day 24 and -0.34 (95% CI, -0.91 to 0.24) for day 26.
  
  
  CONCLUSIONS
  No statistical significant differences in nAPCsr and SHBG levels were found between users of the oral contraceptive containing DNG/E2V and LNG/EE, suggesting a comparable thrombotic risk.
authors: Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. m.raps@lumc.nl
authors: M
authors: M
authors: Raps
authors: F
authors: F
authors: Rosendaal
authors: B
authors: B
authors: Ballieux
authors: J
authors: J
authors: Rosing
authors: S
authors: S
authors: Thomassen
authors: F
authors: F
authors: Helmerhorst
authors: H
authors: H
authors: van Vliet
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood*; D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D012738:Sex Hormone-Binding Globulin; C023635:dienogest; D004958:Estradiol; D009277:Nandrolone