A multicentre study of coagulation and haemostatic variables during oral contraception variations with four formulations
Thomson, J.M.; Poller, L.; Bocaz, J.A.; Barja, P.; Bonnar, J.; Daly, L.; Carrol, A.
British Journal of Obstetrics and Gynaecology 98(11): 1117-1128
1991
ISSN/ISBN: 0306-5456 DOI: 10.1111/j.1471-0528.1991.tb15364.xDocument Number: 341250
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 .mu.g; levonorgestrel (LNG) 250 .mu.g + EE 50 .mu.g; LNG 250 .mu.g + EE 30 .mu.g; LNG 150 .mu.g + EE 30 .mu.g. 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 formation 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 on combined OC on clottig are affected by the type and dose of progestogen as well as the dose of oestrogen.