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

University of Colorado Medical Center, Division of Endocrinology Denver Colorado 80220

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 µg/day) both alone and in combination with mestranol or ethinyl estradiol (10 µg/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 concentrations, mean intravenous serum glucose disappearance rates (K) or mean integrated serum insulin response to glucose (l₄₀). 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 l₄₀). 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 under control conditions. Thus, the IVGTT in the rhesus monkey appears to have limited use as a model for studying glucose homeostasis in man.

¹ These studies were supported by USPHS grant HD-02455. Presented in part at the IV InternationalCongress of Endocrinology, Washington, D.C., June24, 1972. Address reprint requests to Dr. Paul Beck, Box 2325, University of Colorado Medical Center,4200 East Ninth Avenue, Denver, Colorado 80220.

Received January 12, 1973.