title: Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study.
abstract: OBJECTIVE
  The hormonal components of combined oral contraceptives (COCs) have various metabolic and haemostatic effects. The objective of this study was to compare the metabolic and haemostatic effects of a novel COC comprising estradiol valerate/dienogest (E(2)V/DNG) with ethinylestradiol/levonorgestrel (EE/LNG).
  
  
  METHODS
  In a randomized, open-label study conducted in Germany over seven cycles, healthy women aged 18-50 years received E(2)V/DNG (E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26, placebo on days 27-28; n = 30) or EE/LNG (EE 0.03 mg/LNG 0.05 mg on days 1-6, EE 0.04 mg/LNG 0.075 mg on days 7-11, EE 0.03 mg/LNG 0.125 mg on days 12-21, placebo on days 22-28; n = 28). The primary variables were the mean intraindividual relative changes from baseline to cycle 7 in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels. Changes in other lipid parameters, haemostatic parameters, sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), carbohydrate metabolism parameters, blood pressure and body weight were also assessed.
  
  
  RESULTS
  Mean ± SD HDL cholesterol increased by 7.9% ± 21.8% with E(2)V/DNG and decreased by 2.3% ± 14.4% with EE/LNG. Mean ± SD LDL cholesterol decreased by 6.5% ± 15.9% with E(2)V/DNG and by 3.0% ± 17.4% with EE/LNG. Mean ± SD prothrombin fragment 1 + 2 and D-dimer levels remained essentially unchanged in the E(2)V/DNG group (-0.6% ± 30.3% and -2.1% ± 43.5%, respectively), but increased in the EE/LNG group (by 117.3% ± 358.0% and 62.9% ± 99.5%, respectively). Changes in other hepatic-induced parameters (SHBG, CBG) and carbohydrate metabolism were generally less pronounced with E(2)V/DNG versus EE/LNG. Body weight and blood pressure remained stable throughout the study in both treatment groups. Both formulations were well tolerated, with no serious adverse events reported.
  
  
  CONCLUSIONS
  E(2)V/DNG had a minimal impact on metabolic and haemostatic parameters, and a more favourable effect than EE/LNG on lipid markers.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00185224.
authors: Laboratorium fuer Klinische Forschung, Kiel, Germany.
authors: Wolfgang
authors: W
authors: Junge
authors: Bayer HealthCare Pharmaceuticals, Müllerstraβe 178, 13342, Berlin, Germany.
authors: Uwe
authors: U
authors: Mellinger
authors: Bayer HealthCare Pharmaceuticals, Müllerstraβe 178, 13342, Berlin, Germany. susanne.parke@bayer.com.
authors: Susanne
authors: S
authors: Parke
authors: Bayer HealthCare Pharmaceuticals, Müllerstraβe 178, 13342, Berlin, Germany.
authors: Marco
authors: M
authors: Serrani
mesh_terms: D000328:Adult; D050260:Carbohydrate Metabolism; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D004338:Drug Combinations; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005951:Glucose Tolerance Test; D006403:Hematologic Tests; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D009277:Nandrolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013960:Thyroid Function Tests; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D008055:Lipids; C454300:estradiol valerate-dienogest; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone