title: Double-blind, randomized, placebo controlled study on the effects of the monophasic oral contraceptive containing 30 micrograms ethinyl estradiol and 2.00 mg dienogest on the hemostatic system.
abstract: Forty healthy female volunteers aged between 19 and 35 years (27.3 +/- 4.1 years) with normal menstrual cycles were included in a double-blind, randomized, placebo-controlled study to investigate the influence on the hemostatic system of an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest, which is a 19-norprogestin without a 17 alpha-ethinyl group. At baseline and during one treatment cycle, 12 hemostatic parameters were measured on cycle days 7, 14, and 21. The hemostatic parameters were categorized as either procoagulatory, anticoagulatory and profibrinolytic, or antifibrinolytic and indicative of fibrin turnover. Differences between placebo and 30 micrograms ethinyl estradiol and 2.00 mg dienogest of plasma levels of hemostatic parameters on cycle days 21 of the precycle and treatment cycle were chosen as target variables. Prothrombin fragment 1 + 2 (F 1 + 2) was chosen as the main target variable. Equivalence of F 1 + 2 between placebo and active treatment was noted. Among the procoagulatory factors, only factor VII activity was found to be increased over placebo in the active treatment group, but decreased in the placebo group. Protein C activity increased during the treatment with 30 micrograms ethinyl estradiol and 2.00 mg dienogest, and was higher than that of the placebo group in which this parameter decreased during the treatment cycle. There was a corresponding increase in fibrinolytic activity being reflected by higher plasminogen levels in the active treatment group in comparison with placebo. An increase was noted for the fibrinolytic parameter D-dimer. Apart from isolated measurements, the parameters remained in their respective normal ranges. The data combine to suggest that 30 micrograms ethinyl estradiol and 2.00 mg dienogest has a balanced effect on the hemostatic system stimulating both procoagulatory and fibrinolytic activity.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Boltzmann Institute for Experimental Endocrinology, University of Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Spona
authors.forename: W
authors.initials: W
authors.lastname: Feichtinger
authors.forename: C
authors.initials: C
authors.lastname: Kindermann
authors.forename: B
authors.initials: B
authors.lastname: Schneider
authors.forename: U
authors.initials: U
authors.lastname: Mellinger
authors.forename: F
authors.initials: F
authors.lastname: Walter
authors.forename: C
authors.initials: C
authors.lastname: Moore
authors.forename: T
authors.initials: T
authors.lastname: Gräser
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004311:Double-Blind Method; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005167:Factor VII / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D010919:Placebos; D010958:Plasminogen / Q000378:metabolism; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D003276:Contraceptives, Oral; D010446:Peptide Fragments; D010919:Placebos; D011486:Protein C; C045879:prothrombin fragment 1.2; D004997:Ethinyl Estradiol; C023635:dienogest; D009277:Nandrolone; D000990:Antithrombin III; D005167:Factor VII; D011516:Prothrombin; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator