Oral contraceptives, thrombosis and haemostasis.
The use of oral contraceptives is a well-established acquired risk factor for venous thrombosis. In 1995, a number of epidemiological studies were published which suggested that women who use third generation oral contraceptives that contain desogestrel or gestodene as progestagen are exposed to a two- to threefold higher risk for venous thrombosis than women using second generation oral contraceptives which contain levonorgestrel. In this paper, the effects of oral contraceptives on the haemostatic system are discussed. It appears that plasma from oral contraceptive users is resistant to the anticoagulant action of activated protein C (APC). This phenomenon, called acquired APC resistance, is more pronounced in users of desogestrel or gestodene-containing oral contraceptives than in women who use oral contraceptive pills with levonorgestrel. On the basis of these observations, it was proposed that acquired APC resistance may be the mechanistic basis of the increased risk for venous thrombosis during oral contraceptive use and for the further increased thrombotic risk of third generation oral contraceptive users. Furthermore, the results of a recent cross-over study are discussed. This study indicated that a large number of other haemostatic parameters were changed during oral contraceptive use. Some of these changes were more pronounced on desogestrel-containing oral contraceptives. The cross-over study also showed that the increased fibrinolytic activity during OC use is counterbalanced by an enhanced activity of thrombin-activatable fibrinolysis inhibitor (TAFI), a protein that participates in the inhibition of fibrinolysis.
Rosing
J
J
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. j.rosing@bioch.unimaas.nl
Curvers
J
J
Tans
G
G
D020016:Activated Protein C Resistance / Q000139:chemically induced / Q000235:genetics; D003276:Contraceptives, Oral / Q000009:adverse effects*; D017135:Desogestrel / Q000009:adverse effects; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D009652:Norpregnenes / Q000009:adverse effects; D012307:Risk Factors; D020246:Venous Thrombosis / Q000139:chemically induced*
D003276:Contraceptives, Oral; D009652:Norpregnenes; C033273:Gestodene; D017135:Desogestrel