Effects of smoking on prostacyclin formation and platelet aggregation in users of oral contraceptives.
OBJECTIVE
The aim of this review was to determine which subgroups within the population of smokers and oral contraceptive users are at especially elevated risk for thromboembolic events.


METHODS
This review covers 10 articles published between 1981 and 1996 that examined the effects of smoking and oral contraceptive use, in conjunction or independently, on factors affecting the coagulation pathway, particularly the expressions of prostacyclin and thromboxane.


RESULTS
Heavy, prolonged, or current nicotine use was associated with a reduction in the urinary metabolite of prostacyclin (prostaglandin I2) in oral contraceptive users. Smoking and increased excretion of thromboxane were also linked, and in 1 study the effect was dose related. These changes were associated with increased platelet aggregation. Oral contraceptive use and concurrent smoking increased the risk of acute myocardial infarction by a ratio of 10.1. Although most of this risk was seen among smokers who used second-generation oral contraceptives (odds ratio 11.1), with a much reduced odds ratio for smokers who used third-generation oral contraceptives (odds ratio 3.1), the study was not controlled for estrogen dose. A reduction in myocardial infarction risk compared with that in the 1970s was seen for all oral contraceptive users, probably because of the reduced hormonal doses in current preparations.


CONCLUSIONS
Smoking, not oral contraceptive use, constitutes the greater cardiovascular risk. However, cigarette smoking and oral contraceptive use act synergistically to increase the risk of thromboembolic events. Differences in oral contraceptive formulations may mitigate the increased risk resulting from concurrent smoking and use of oral contraceptives, but whether the progestin component or the lowered estrogen dose is responsible is unclear.
Roy
S
S
Women's and Children's Hospital, Los Angeles, California, USA.
D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000209:etiology; D003276:Contraceptives, Oral / Q000009:adverse effects*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D009203:Myocardial Infarction / Q000139:chemically induced / Q000209:etiology; D010974:Platelet Aggregation / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*; D013923:Thromboembolism / Q000139:chemically induced / Q000209:etiology
D003276:Contraceptives, Oral; D011464:Epoprostenol