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Metabolic and Haemostatic Effects of Estradiol Valerate/Dienogest, a Novel Oral Contraceptive

A Randomized, Open-Label, Single-Centre Study

Abstract

Background and 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 (E2V/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 E2V/DNG (E2V 3 mg on days 1–2, E2V 2 mg/DNG 2 mg on days 3–7, E2V 2 mg/DNG 3 mg on days 8–24, E2V 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 E2V/DNG and decreased by 2.3%±14.4% with EE/LNG. Mean ± SD LDL cholesterol decreased by 6.5% ±15.9% with E2V/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 E2V/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 arameters (SHBG, CBG) and carbohydrate metabolism were generally less pronounced with E2V/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.

Conclusion: E2V/DNG had a minimal impact on metabolic and haemostatic parameters, and a more favourable effect than EE/LNG on lipid markers.

Trial registration:} ClinicalTrials.gov Identifier: NCT00185224

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Acknowledgements

This study was funded by Bayer HealthCare Pharmaceuticals, Berlin, Germany, the manufacturer of estradiol valerate/dienogest. Medical writing services during the preparation of this manuscript were provided by Lyndal Staples and Danielle Turner (inScience Communications, a Wolters Kluwer business, Chester, UK). Funding for this editorial assistance was provided by Bayer HealthCare Pharmaceuticals.

Uwe Mellinger, Susanne Parke and Marco Serrani are current employees of Bayer HealthCare Pharmaceuticals. Wolfgang Junge is the Medical Director of Laboratorium fuer Klinische Forschung, the center at which all laboratory tests were performed.

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Correspondence to Dr Susanne Parke.

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Junge, W., Mellinger, U., Parke, S. et al. Metabolic and Haemostatic Effects of Estradiol Valerate/Dienogest, a Novel Oral Contraceptive. Clin. Drug Investig. 31, 573–584 (2011). https://doi.org/10.2165/11590220-000000000-00000

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Keywords

  • Combine Oral Contraceptive
  • Dienogest
  • Prothrombin Fragment
  • SHBG Level
  • Drospirenone