Defects in carbohydrate metabolism in oral contraceptive users without apparent metabolic risk factors

Abstract

We performed oral glucose tolerance tests and frequently sampled iv glucose tolerance tests in a cross-sectional sample of women taking monophasic norgestrel containing oral contraceptives (OC). The goal of the study was to quantify the individual factors that determine glucose tolerance to assess responsibility for the reduced glucose tolerance associated with the use of OCs. Subjects were selected using stringent criteria to exclude confounding effects of ethnicity, adiposity, or conditions that may predispose subjects to metabolic disorders. Users of the low dose OC (Lo/Ovral and Nordette) and high dose OC (Ovral) were compared to controls, who were required to never have used OCs or to have discontinued OC use for at least 24 months. Oral glucose tolerance tests results confirmed the development of impaired glucose tolerance in both pill groups. Frequently sampled iv glucose tolerance test data were analyzed using the minimal model method to estimate parameters of insulin sensitivity, glucose effectiveness (SG), and beta-cell function. Lo/Ovral users had lower insulin sensitivity and SG compared to controls and inappropriately low beta-cell function in relation to the insulin resistance. Ovral users had metabolic parameters that were not different from controls. Based upon comparisons between normal and impaired glucose tolerant subjects combined with stepwise regression analysis, we conclude that Lo/Ovral use results in insulin and glucose resistance, which is not compensated by increased beta-cell function. The reduced glucose tolerance is due primarily to the defect in SG, and these OC users may place themselves at higher risk for the development of diabetes or cardiovascular disease. The reduced tolerance in Ovral users cannot be explained by the parameters measured in this study. We speculate that these latter subjects represent a special self-selected population in which tolerance is regulated by other factors. Ovral appears to be well tolerated by these women.