Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study.

Author(s): Junge W, Mellinger U, Parke S, Serrani M

Affiliation(s): Laboratorium fuer Klinische Forschung, Kiel, Germany.

Publication date & source: 2011, Clin Drug Investig., 31(8):573-84.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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 (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. CONCLUSION: E(2)V/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.