Oral contraceptive (OC) use is a risk for thrombogenic events. This paper reviews effects of OC on oxidative status, coagulation, and platelet activity. Complicating effects of cardiovascular risk factors such as smoking, diabetes, hyperpidemia, and hypertension, are discussed. From these data we conclude that: 1. OC use modifies slightly but significantly the oxidative status in women and in animals by decreasing in plasma and blood cells the antioxidant defenses (vitamins and enzymes). 2. The changes in the oxidative status are related to an increase in plasma lipid peroxides apparently responsible for the hyperaggregability and possibly the imbalance in clotting factors associated with the OC-induced prethrombotic state. 3. These effects of OC appear to be increased by a high intake of polyunsaturated fat and counteracted by supplements of vitamin E. 4. The risk factors acting synergistically with OC, have all been shown to increase platelet reactivity. In addition, smoking, diabetes, and, to some extent, dyslipidemia are associated with an increased level of lipid peroxides and concomitant changes in the antioxidant defenses that can be additive to those induced by OC. Thus, free radicals and lipid peroxidation could be the underlying mechanism in the predisposition to thrombosis induced by most risk factors in OC users. 5. Results of epidemiologic and experimental studies in this field will be concordant only when diet and natural antioxidants will be systematically taken into consideration.
PIP: Although any cardiovascular complications of combined oral contraceptive (OC) use have dramatically increased in the past decade, both as a result of lower dosages (under 50 mcg) of estrogen in newer OCs and the recommendation that this method be used only by nonsmokers under 35 years of age, there remains a need to deepen understanding of the mechanisms involved. The increased levels of estrogen in OCs, associated with free radical generation, lead to a disruption in oxidative status. Further deterioration occurs when other risk factors (smoking, diabetes, or nutritional insufficiency) that also induce the production of free radicals and promote lipid peroxidation are present. The increase in plasma lipid peroxides appears to be responsible for the hyperaggregability and imbalance in clotting factors associated with the OC-induces thrombotic state. This hyperaggregability is modulated in OC users by the intake of polyunsaturated fan and antioxidants. Key to the avoidance of thrombotic events in OC users is the screening out of potential acceptors with risk factors such as smoking that act synergistically with OCs. Determination of platelet reactivity should be considered in questionable cases. Since vitamin E has been shown to improve platelet reactivity and oxidative status in OC users, its addition directly to the pill should be considered as a preventive measure. Now that the link between thrombogenic mechanisms and lipid peroxidation has been established, research should be undertaken to separate the estrogenic from the free radical-inducing properties of OCs.