Prospective studies of insulin sensitivity in normal women receiving oral contraceptive agents

Seven normal premenopausal women were studied before (control) and after 3 and 6 months of oral contraceptive agent (OCA) administration (30 micrograms ethinyl estradiol plus 150 micrograms levonorgestrel). The plasma glucose responses during 75-g oral glucose tolerance tests were not altered by the OCA, but the 3- and 6-month plasma insulin responses significantly exceeded control values (P less than 0.05). On a separate morning a constant iv infusion of [3H]3-glucose was given throughout a 2-h basal period and during two successive 2-h euglycemic clamp procedures at iv insulin delivery rates of 10 and 40 mU/m2.min, respectively. Endogenous glucose production rates (milligrams per kg/min) were not altered after 3 or 6 months of OCA administration. Peripheral glucose utilization rates were expressed as M (milligrams per kg/min) or the ratio of M over the prevailing plasma insulin concentration (M/I). One or both parameters were significantly reduced below control values at both insulin infusion rates after 3 months (P less than 0.05), but returned toward control values after 6 months. Serum androgen concentrations were reduced or not altered by OCA administration. We conclude that insulin resistance induced by OCA administration is manifested by reduced peripheral tissue insulin sensitivity and may ameliorate with time. This effect does not relate consistently to total plasma insulin responses during oral glucose tolerance tests or to elevated serum androgen concentrations.