title: Effects of second and third generation oral contraceptives and their respective progestagens on the coagulation system in the absence or presence of the factor V Leiden mutation.
abstract: Compared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis especially in women with the factor V Leiden mutation. To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation. In a single center, double blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third generation (30 microg ethinylestradiol/150 microg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of 2 menstrual cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel. In plasmas of the participating women fragment 1+2, factor V, VII, VIII, IX, X and XI were determined. Both combined oral contraceptives induced a decrease in factor V, whereas the levels of all other coagulant parameters increased. However, in women without the factor V Leiden mutation the effects of desogestrel-containing preparations were significantly different compared to levonorgestrel-containing oral contraceptives for factor V (-8.0; 95% CI -13.4 to -2.6), factor VII (26.8; 95% CI 15.5 to 38.0) and factor IX (-9.6; 95% CI -16.2 to -3.2). When these women used progestagen-only pills, a differential effect between desogestrel and levonorgestrel was only found for factor IX (-6.5; 95% CI -11.4 to -1.5). In carriers of the factor V Leiden mutation desogestrel-containing oral contraceptives induced more pronounced changes in factor V (-14.2; 95% CI -22.4 to -6.0) and factor VII (36.1; 95% CI 19.7 to 52.6) compared to levonorgestrel-containing oral contraceptives. Comparing desogestrel- and levonorgestrel-only, only for factor V a differential effect was found in these women (-9.5; 95% CI -18.3 to -0.6). It appears that desogestrel-containing oral contraceptives have a more pronounced effect on the coagulation system than levonorgestrel-containing oral contraceptives which may be explained by a less effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.
authors.affiliation: Julius Center for General Practice and Patient Oriented Research, University Medical Center Utrecht, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Kemmeren
authors.forename: A
authors.initials: A
authors.lastname: Algra
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: B N
authors.initials: BN
authors.lastname: Bouma
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood / Q000235:genetics*; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000032:analysis*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000494:pharmacology; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects* / Q000494:pharmacology; D017135:Desogestrel / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004311:Double-Blind Method; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D005164:Factor IX / Q000032:analysis; D005165:Factor V / Q000032:analysis / Q000235:genetics*; D005167:Factor VII / Q000032:analysis; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced* / Q000235:genetics
chemical_list: D001779:Blood Coagulation Factors; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D010446:Peptide Fragments; C095381:factor V Leiden; C045879:prothrombin fragment 1.2; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D017135:Desogestrel; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX