Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women

Am J Obstet Gynecol. 1993 Jan;168(1 Pt 1):32-8. doi: 10.1016/s0002-9378(12)90880-7.

Abstract

Objective: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens.

Study design: Thirty-four healthy young women were allocated to 12 consecutive cycles of treatment with monophasic combinations of 20 micrograms ethinyl estradiol and 150 micrograms desogestrel (n = 15) or 30 micrograms ethinyl estradiol and 75 micrograms gestodene (n = 19). Nonparametric analysis of variance was used for statistical evaluation.

Results: In both groups plasma levels of fibrinogen and Factor VIIc increased, and the capacity of coagulation inhibition was affected by increased protein C and decreased protein S levels. Increased fibrinolytic capacity was indicated by elevated activity and reduced antigen levels of tissue plasminogen activator and by reduced activity and concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis.

Conclusion: The overall dynamic balance between generation and resolution of fibrin was maintained during treatment with both hormonal compounds. Our findings suggest that the risk of thrombosis in normal women should not be increased.

PIP: Cardiovascular disorders observed in women using combined oral contraceptives have been linked to alterations in hemostatic function and in lipoprotein and carbohydrate metabolism. In the coagulation system, concentrations of vitamin-K-dependent coagulation factors tend to increase with decreased, increased, or unchanged concentrations of the inhibitors of coagulation. Some changes have also been seen in the fibrinolytic system; particularly with regard to increased capacity. The influence of oral contraceptives upon the two systems depends mainly upon estrogen dose. The possibility therefore exists that the changes in hemostatic variables and the occurrence of thromboembolism may be associated as suggested by the reported decrease in vascular morbidity with reduced estrogen dose. The authors report findings from their evaluation of the influence on coagulation and fibrinolysis of two combined oral contraceptives containing ethinyl estradiol in monophasic combination with the newly developed progestogens desogestrel and gestodene with respect to the capacity within the two systems and their dynamic balance by means of intermediate reaction products over a 12-month period. 34 healthy young women aged 21-30 years with no evidence of current or past liver disease or thromboembolic disorders were allocated to 12 consecutive cycles of treatment with the combinations. All participants had normal blood pressure and were within 10% of their ideal body weight. 15 women received a combination of 20 mcg ethinyl estradiol and 150 mcg desogestrel, while 19 women received 30 mcg ethinyl estradiol and 75 mcg gestodene. The overall dynamic balance between generation and resolution of fibrin was maintained during treatment with both hormonal compounds. These findings suggest that the risk of thrombosis in normal women should not be increased as a result of such treatment regimes.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Coagulation / drug effects*
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / chemistry
  • Contraceptives, Oral, Combined / pharmacology*
  • Desogestrel / administration & dosage
  • Desogestrel / pharmacology*
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacology*
  • Female
  • Fibrin / drug effects
  • Fibrin / metabolism
  • Fibrinolysis / drug effects*
  • Humans
  • Norpregnenes / administration & dosage
  • Norpregnenes / pharmacology*

Substances

  • Contraceptives, Oral, Combined
  • Norpregnenes
  • Gestodene
  • Ethinyl Estradiol
  • Desogestrel
  • Fibrin