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Title: Oral contraceptives and coronary heart disease: modulation of glucose tolerance and plasma lipid risk factors by progestins. Author: Crook D, Godsland IF, Wynn V. Journal: Am J Obstet Gynecol; 1988 Jun; 158(6 Pt 2):1612-20. PubMed ID: 3287933. Abstract: Widespread use of oral contraceptive formulations by women throughout their reproductive life has given rise to concerns about the effects of oral contraceptives on risk factors for coronary heart disease. Oral contraceptive-induced changes in both carbohydrate and lipoprotein risk factors may contribute to an increased risk of coronary heart disease. Carbohydrate and lipoprotein risk factors for coronary heart disease are reviewed, and oral contraceptive-induced changes in carbohydrate and lipoprotein metabolism, which may lead to altered risk status for coronary heart disease, are discussed. The importance of methodology in evaluating the results of studies assessing such oral contraceptive-induced changes is stressed. The role of progestins in influencing coronary heart disease risk factors is surveyed, and differences among progestins commonly used in oral contraceptive formulations are discussed. In addition, the effect of various combination oral contraceptives on risk factor status is outlined. Finally, the implications of available evidence for the selection of progestins for oral contraceptive formulations of the future are discussed. Current data indicate that medium- and low-fixed-dose oral contraceptive formulations containing estrogen/norethindrone acetate have less metabolic impact than do comparable levonorgestrel-containing formulations, including multiphasic formulations. Triphasic formulations may have less effect on coronary heart disease risk factors, although data are not yet conclusive. Novel progestins such as desogestrel may also have lesser effects on metabolic functions, but the reduced androgenicity of such compounds may expose women to an increased risk of estrogen-induced hypertriglyceridemia. A summary of the lipoprotein and carbohydrate risk factors for coronary heart disease associated with use of oral contraceptives is followed by a discussion of the methodological difficulties in measuring them, and then by a description of the properties of commonly used oral steroids. Impaired glucose tolerance, high insulin levels, reduced HDL cholesterol and increased LDL cholesterol and VLDL triglycerides are features of coronary heart disease, diabetes, obesity and use of oral contraceptives. A more accurate assessment of glucose tolerance may be measurement of the plasma C-peptide of insulin. Lipid risk factors are subject to wide individual variation as well as special difficulties for pill users. For example, the convenient dextran sulfate method of precipitating HDL, from which the LDL value is calculated, may not be accurate for pill takers because of elevated triglycerides. Even assay of apolipoprotein B is subject to this distortion. If apolipoprotein methods can be standardized, assay of apolipoprotein A1, corresponding to the HDL2 subclass, may be appropriate. Progestins of the gonane class, such as levonorgestrel, because of their androgenic activity, induce changes in lipid risk factors in women similar to those of men. The net effect of the combination of estrogen and progestin is what matters, however. Although progestin-only pills have no effect on carbohydrate metabolism, combined pills decrease glucose tolerance with time, induce hypertriglyceridemia, and oppose the tendency of the estrogen to increase HDL. Norethindrone or other estrane compounds have less impact. Data on triphasics are sparse, but suggest a lesser effect also. New progestins with lower androgenic effects are being developed, although they may confer the added risk of increased triglycerides. Parenteral steroid administration or use of natural hormones are potential solutions.[Abstract] [Full Text] [Related] [New Search]