The effect of oestrogen dose and progestogen type on haemostatic changes in women taking low dose oral contraceptives

Abstract

Objective: To determine the effect of oestrogen dose and progestogen type on the coagulation and fibrinolytic systems of a group of normal healthy women taking three different oral contraceptive combinations.

Design: Plasma levels of factor VII, X, antithrombin III, protein C, fibrinogen, tissue plasminogen activator activity, plasminogen activator inhibitor I antigen and fibrin (D-dimer) degradation products were measured at pretreatment, 6, 14, 22 weeks of treatment and at 6 weeks post-treatment in a group of 67 women taking either 30 micrograms ethinyloestradiol/150 micrograms desogestrel (n = 21), 20 micrograms ethinyloestradiol/150 micrograms desogestrel (n = 24), 30 micrograms ethinyloestradiol/75 micrograms gestodene (n = 22).

Participants: Sixty-seven healthy normal women, 18 to 34 years, smoking fewer than 15 cigarettes per day. The subjects were within 10% of their normal body weight and had no history of thromboembolic disease.

Setting: Coombe Women's Hospital and St James's Hospital, Dublin, Ireland.

Results: Factor VII and X levels were significantly raised on treatment with both the 30 micrograms ethinyloestradiol/desogestrel and gestodene combinations. Higher levels of factor VII activity were observed in the 30 micrograms ethinyloestradiol/desogestrel combination compared with the gestodene combination. Factor VII and X were not significantly affected by the 20 micrograms ethinyloestradiol combination. Increased plasminogen, fibrinogen and D-dimer levels and decreased plasminogen activator inhibitor I antigen levels were observed during the treatment phases in all three groups. Antithrombin III and protein C activity did not change during treatment with any of the oral contraceptives studied.

Conclusions: Low dose oral contraceptives cause an activation of the coagulation system which is balanced by an activation of the fibrinolytic system. Reducing the dose of ethinyloestradiol from 30 micrograms to 20 micrograms reduces the effect on factor VII and X. This effect can be modified by the progestogen. The lesser effect of the 20 micrograms combination may make this a safer option for some women than pills containing a higher dose of oestrogen.

PIP: At Coombe Women's Hospital and St. James's Hospital in Dublin, Ireland, health researchers randomly assigned 67 healthy women aged 18-34 years to receive one of three low-dose combined oral contraceptives (OCs) so they could investigate the effect of the estrogen and the progestogen on the activation and inhibition of the coagulation and fibrinolytic systems. Two of the OCs contained 150 mcg desogestrel (DES) and either 30 mcg or 20 mcg ethinyl estradiol (EE). The third OC contained 30 mcg EE and 75 mcg gestodene (GES). The women were followed for 28 weeks. The two OCs with 30 mcg E2 significantly increased factor VII and X levels (p 0.01). The 30-mcg EE/DES OC effected an even higher increase of factor VII activity (p 0.001). The 20-mcg EE/DES OC did not significantly affect factor VII and X activity. All three OCs increased plasminogen, fibrinogen, and D-dimer levels and reduced plasminogen activator inhibitor I antigen levels. None of the OCs changed antithrombin III and protein C activity. In conclusion, these OCs activated the blood coagulation system as well as the fibrinolytic system. Specifically, activation of the fibrinolytic system balances the activation of the coagulation system. The progestogen can reduce the effect of a lower EE dose on factor VII and X. The reduced effect of the 20-mcg EE combined OC suggests that it may be a safer option for some women than the higher EE dose OCs.