Effect of four oral contraceptives on hemostatic parameters.
This is the first double-blind, controlled, randomized study comparing the effect of different estrogen components in oral contraceptives (OCs) on hemostasis variables. Four groups of 25 women each were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). Blood samples were taken on Days 21-26 of the control cycle and on Days 18-21 of the first, third and sixth treatment cycle. Treatment with all four OCs caused an increase in levels of fibrinogen, prothrombin fragment 1+2, D-dimer, plasminogen, plasmin-antiplasmin complex and an increase in protein C activity, a decrease in antithrombin activity, tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), and a slight decrease in the sensitivity to activated protein C, but no significant change in that of the thrombin-antithrombin complex. In users of the DNG-containing OCs, the reduction in total and free protein S, and in t-PA and PAI was dependent on the EE dose, while factor VII activity was elevated, but not significantly different from EE/LNG. The results are in agreement with those of previous studies. The effects of EE/EV/DNG on total and free protein S and on t-PA and PAI were lower than those of 20EE/DNG, suggesting that the impact of 2 mg EV on several hemostasis variables is less than that of 10 microg EE. The results show an antagonistic effect of LNG on the EE-induced rise of factor VII activity and fragment 1+2 and on the EE-dependent reduction of total and free protein S.
Center of Obstetrics and Gynecology, University Hospital of Frankfurt, Frankfurt am Main, Germany.
I
I
Wiegratz
J H
JH
Lee
E
E
Kutschera
U H
UH
Winkler
H
H
Kuhl
D000991:Antithrombins / Q000032:analysis; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D005167:Factor VII / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects; D009277:Nandrolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010446:Peptide Fragments / Q000097:blood; D010958:Plasminogen / Q000032:analysis; D015849:Plasminogen Inactivators / Q000097:blood; D011486:Protein C / Q000032:analysis; D011516:Prothrombin; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000032:analysis
D000991:Antithrombins; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D015849:Plasminogen Inactivators; D011486:Protein C; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; C037742:plasmin-plasmin inhibitor complex; C045879:prothrombin fragment 1.2; D004997:Ethinyl Estradiol; C023635:dienogest; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone; D005167:Factor VII; D011516:Prothrombin; D005340:Fibrinogen; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin