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[Oral contraceptives and metabolic changes].


 Sufficient evidence has accumulated to relate oral contraceptives (OCs) to various cardiovascular diseases in which metabolic alterations play a role. Although epidemiological studies have shown OC users to be at greater risk of venous thrombosis than nonusers, blood coagulation studies of OC users have yielded conflicting results due to variations in the methodologies used, the factors studied, the different formulations and doses of OCs, and the duration of use. Moreover, no satisfactory method exists of measuring coagulability in its totality, which is the sum of the effects of individual variations in coagulation factors, fibrinolysis, and platelet function. Numerous studies have shown that OC users have increased levels of several coagulation factors, which are believed to indicate hypercoagulability and increased risk of thrombosis, but the pathogenesis of venous thrombosis is complex. Accompanying changes in the fibrinolytic system can be interpreted as attempts to equilibrate the hypercoagulability induced by OCs. Further, there is no proof that in vitro changes are related to thrombosis in vivo. The alterations appear to be dose-related, produced primarily by estrogens, unrelated to duration of use, and to disappear a few months after termination of OC use. OC users have been shown repeatedly to have elevated levels of glucose and insulin, which are especially pronounced in glucose tolerance tests. The changes vary in intensity according to the dose and progestational components and the existence of other risk factors for diabetes. Deterioration of glucose tolerance appears related to duration of OC use, but serum insulin levels maintain the same initial elevations. The estrogens have been shown to have few effects on carbohydrate metabolism in the lower doses currently used. Norgestrel has the most marked effects on glucose and insulin levels, ethynodiol diacetate has moderate effects, and norethindrone has the least effect. The combination of .15 mg levonorgestrel and 30 mcg ethinyl estradiol has no effect on oral glucose tolerance and little effect on insulin secretion. It is hypothesized that OCs affect carbohydrate metabolism by decreasing the number and affinity of insulin receptors in target tissues. The mechanisms by which OCs produce undesirable effects on the cardiovascular system are not completely understood, but are believed to be related to alterations in lipid metabolism. The majority of laboratory studies have shown that OC users had elevated levels of cholesterol, triglycerides, and the (LDL) fractions, and a diminution of the high density lipoprotein (HDL) fraction, which has antiatherogenic properties. The changes are atherogenic in nature and produce a lipid profile similar to that of men and postmenopausal women, who are at greater risk of thrombotic cardiovascular disease that premenopausal women who are protected by estrogens. .
