The effects of oral contraceptives on coagulation in 258 nonsmoking and in 190 smoking women were determined. In smokers and in nonsmokers taking oral contraceptives, fibrinogen and fibrinopeptide A concentrations were higher than in oral contraceptive nonusers. In nonsmokers, oral contraceptives increased antithrombin III activity. The effects on coagulation of oral contraceptives with a different ethinylestradiol content (from 35 mcg to 20 mcg) were then evaluated in 333 of these women. The biggest changes in coagulation were observed in smokers taking the preparation with the highest estrogen content. Reduction of the ethinylestradiol dose caused a decrease of the changes in coagulation induced by oral contraceptives both in smokers and nonsmokers. These results might suggest that during oral contraception the coagulation system is affected mainly in smokers and that the decrease of the estrogen dose might lower the effects of the association of smoking and oral contraception on coagulation.
PIP: The synergistic effect of cigarette smoking and oral contraceptive (OC) use on hemostasis was investigated in 448 healthy volunteers aged 17-46 years of age recruited from a family planning clinic in Italy. 190 subjects were smokers and 77 were current OC users; 33 of the OC users were also smokers. To be eligible for study participation, OC users had to be on formulations that contained no more than 35 mcg of ethinyl estradiol and to have at least 6 months of use. The OC users were randomly assigned to one of the following regimens: a monophasic OC containing 35 mcg of ethinyl estradiol and 2 mg of cyproterone acetate, two monophasic pills with 30 mcg of ethinyl estradiol and 75 mcg of gestodene or 150 mcg of desogestrel, or one monophasic combination of 20 mcg of ethinyl estradiol and 150 mcg of desogestrel. Overall, the findings confirmed that OC-related changes in blood coagulation are evident mainly in smokers. OC users who smoked had significantly higher plasma levels of fibrinogen and fibrinopeptide A as well as prothrombin activity values than nonsmoking OC users. However, OC use did not increase antithrombin III activity in smokers. The effect of smoking on blood coagulation factors was not affected by age or number of cigarettes smoked per day (although there were no heavy smokers in the study). An ethinyl estradiol dose-response effect was evident on hemostasis in all OC groups, but the changes in coagulation factors at higher doses were more pronounced in smokers than in nonsmokers.