Mutual Modification of Glucose-Stimulated Serum Insulin Responses in Female Rhesus Monkeys by Ethinyl Estradiol and Nortestosterone Derivatives1

Changes in iv glucose tolerance (IVGTT) and serum insulin responses to glucose infusion have been measured in intact female rhesus monkeys treated per os with norethindrone or medroxyprogesterone acetate (500 mug/day) both alone and in combination with mestranol or ethinyl estradiol (10 mug/day) orally for 3 weeks. When administered as the sole contraceptive steroid, neither norethindrone, medroxyprogesterone acetate, mestranol, or ethinyl estradiol produced consistent changes in fasting serum insulin or glucose concentration, mean intravenous serum glucose disappearance rates (K) or mean integrated serum insulin response to glucose (sigmal40). By contrast, concurrent administration of norethindrone with mestranol or ethinyl estradiol resulted in a significant increase in the fasting serum insulin concentration and the mean sigmal40. An increase in the mean K was also observed after norethindrone + mestranol. These results show that synthetic estrogens have the ability to potentiate the metabolic effects of norethindrone. However, the improvement in glucose tolerance produced in rhesus monkeys by concurrent mestranol + norethindrone treatment was marginal because of wide variation in glucose assimilation rates uncer control conditions. Thus, the IVGTT in the rhesus monkey appears to have limited use as a model for studying glucose homeostasis in man.