Hemostatic effects of smoking and oral contraceptive use

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 2):S369-74. doi: 10.1016/s0002-9378(99)70698-8.


This review addresses current knowledge of the effects of lower dose oral contraceptives (containing 35, 30, or 20 micrograms of ethinyl estradiol) on hemostasis in smoking and nonsmoking women. Evidence suggests that formulations containing 30 and 35 micrograms ethinyl estradiol induce a significant activation of coagulation, whereas oral contraceptive preparations with 20 micrograms ethinyl estradiol appear to have a negligible effect or no effect. In nonsmokers who take oral contraceptives any procoagulatory effects that may occur are counterbalanced by fibrinolytic effects. In smokers, however, compensatory fibrinolytic effects to offset the procoagulatory effects seen with 30-micrograms ethinyl estradiol oral contraceptive formulations are absent, shifting the hemostatic profile toward a hypercoagulable state. This suggests that a formulation with the lowest dose of ethinyl estradiol may be most suitable for smokers who wish to use this form of contraception.

PIP: This review addresses current knowledge of the effects of lower-dose oral contraceptives (OCs) (containing 35, 30, or 20 mcg of ethinyl estradiol) on hemostasis in smoking and nonsmoking women. Data showed that the OCs containing 30-35 mcg ethinyl estradiol influence a significant activation of coagulation parameters compared to the 20-mcg formulations, which appear to have little or no procoagulatory effect. However, procoagulatory effects of these OCs showed to be counterbalanced by the compensatory anticoagulation effects within the fibrinolytic system. This would indicate that most healthy women taking lower-dose OCs, particularly those containing 20 mcg ethinyl estradiol, are not at increased risk for thromboembolic disease. However, this compensatory activity of the fibrinolytic system does not occur in women who both smoke and use OCs. Studies documented that simultaneous smoking and OC use could lead to hypercoagulation. This suggests that OCs with the lowest effective dose of ethinyl estradiol are the best contraceptives for smokers.

MeSH terms

  • Blood Coagulation / drug effects
  • Contraceptives, Oral / adverse effects*
  • Dose-Response Relationship, Drug
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / adverse effects
  • Female
  • Fibrinolysis / drug effects
  • Hemostasis / physiology*
  • Humans
  • Reference Values
  • Smoking / adverse effects*


  • Contraceptives, Oral
  • Ethinyl Estradiol