A multicentre study of coagulation and haemostatic variables during oral contraception: variations with four formulations. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland.

OBJECTIVE

To explore the extent to which progestogen type and oestrogen and progestogen dose may modify the effects of combined oral contraceptives (OC) on coagulation and haemostasis.

DESIGN

Randomized double-blind clinical trial.

SETTING

Gynaecological clinics in Salvador (Brazil), Santiago (Chile), Singapore, and Dublin (Ireland).

SUBJECTS

622 women aged 18-35 years who had opted for oral contraception. A contrast group of 155 women who were not to receive OC was also studied. Both groups included approximately equal numbers from each of the four centres.

INTERVENTIONS

Treatment of approximately equal numbers of women at each centre with one of the following OC preparations for at least 12 months: Norethisterone acetate (NEA) 1 mg + ethinyl oestradiol (EE) 50 micrograms; levonorgestrel (LNG) 250 micrograms + EE 50 micrograms; LNG 250 micrograms + EE 30 micrograms; LNG 150 micrograms + EE 30 micrograms.

MAIN OUTCOME MEASURES

Changes over 12 months in 12 coagulation and haemostatic variables.

RESULTS

At 12-month follow-up, the women on each OC preparation showed acceleration of prothrombin time and increase in factor X and fibrinogen. With the OC containing NEA there was also a persistent rise in factor VIIC, and reduction of antithrombin III and alpha 2-antiplasmin. The formulation which contained low doses of both LNG and EE showed the least adverse coagulation changes. Large increases in fibrinolysis were found in all OC groups.

CONCLUSIONS

The adverse effects of combined OC on clotting are affected by the type and dose of progestogen as well as the dose of oestrogen.