An open-label, comparative study of the effects of a dose-reduced oral contraceptive containing 0.02 mg ethinylestradiol/2 mg chlormadinone acetate on hemostatic parameters and lipid and carbohydrate metabolism variables.
OBJECTIVE
The study was conducted to compare the effects of 0.02 mg ethinylestradiol (EE)/2 mg chlormadinone acetate (CMA), given for 24 days each cycle, with those of 0.02 mg EE/0.15 mg desogestrel (DSG) and 0.03 mg EE/0.15 mg levonorgestrel (LNG), given for 21 days each cycle, on hemostatic, lipid, and carbohydrate metabolism parameters in healthy subjects, over six medication cycles.


METHODS
A randomized, multicentre, open-label, Phase II trial measured markers of hemostasis, and of lipid and carbohydrate metabolism in 165 subjects randomly assigned to treatment with one of three combined oral contraceptives (COCs).


RESULTS
EE/CMA and EE/DSG had a similar effect on hemostatic parameters, the EE/LNG group showed comparatively smaller increases in the activity of factor VII [8.1% vs. 36.6% (EE/CMA) and 28.2% (EE/DSG)], protein C [5.9% vs. 32.9% (EE/CMA) and 21% (EE/DSG)] and endogenous thrombin potential-based activated protein C resistance [44.1% vs. 93.5% (EE/CMA) and 108.1% (EE/DSG)], and in contrast, free protein S levels decreased in the EE/CMA and EE/DSG groups (-12.7% and -4.3%, respectively) but rose in the EE/LNG group (20.4%). In all treatments, total cholesterol, total triglyceride and apolipoproteins increased. Levels of very low-density lipoprotein cholesterol particularly rose across all groups. Slight increases in high-density lipoprotein (HDL) cholesterol were observed for EE/CMA (14.6%) and EE/DSG (8.5%), with a rise above the upper limit of normal in 30% of the subjects taking EE/CMA. Conversely, for EE/LNG slight decreases in HDL cholesterol were observed (-12.4%) lipoprotein (a) levels decreased in the EE/CMA (-6.6%) and EE/LNG (-16.9%) groups and were unchanged in the EE/DSG group.


CONCLUSIONS
The changes observed were typical of those seen across low-dose COCs that differ according to commonly-used progestogens.
Winkler
Ulrich H
UH
Department of Gynaecology and Obstetrics, Clinic of Wetzlar-Braunfels, Wetzlar, Germany. ulrich.winkler@lahn-dill-kliniken.de
Röhm
Petra
P
Höschen
Kornelia
K
D000293:Adolescent; D000328:Adult; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002715:Chlormadinone Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D017135:Desogestrel / Q000494:pharmacology; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects*; D055815:Young Adult
D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; C072593:ethinyl estradiol, levonorgestrel drug combination; C442659:ethinyl estradiol-desogestrel combination; C488302:ethinylestradiol-chlormadinone acetate; D002715:Chlormadinone Acetate; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D017135:Desogestrel