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Micronized Estradiol and Progesterone: Effects on Carbohydrate Metabolism in Reproductive-Age Women

Yale University School of Medicine, New Haven, Connecticut; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1230

Ralph A. DeFronzo, MD

Robert S. Sherwin, MD

Michael P. Diamond, MD

Yale University School of Medicine, New Haven, Connecticut

Objective: We assessed glucose utilization and insulin sensitivity in normal reproductive-age women after administration of micronized estradiol, micronizedprogesterone, or the combination of micronized estradiol and progesterone.

Methods: Hyperglycemic and euglycemic, hyperinsulinemic clamp studies were performed in normal, regularly cycling women both before and after a short course of either micronized estradiol (n = 8), micronized progesterone (n = 8), or micronized estradiol and progesterone (n = 7). All studies were performed after an overnight fast. Glucose and insulin were determined in the control period and then every 2-10 minutes in the hyperglycemic clamp studies and every 5-10 minutes in the euglycemic clamp studies. In the hyperglycemic clamp studies, hyperglycemia was maintained by a variable glucoseinfusion. In the euglycemic clamp studies, a primed 3-³H glucose infusion (25 µCi continuous infusion was begun 120 minutes before initiation of the insulin infusion and variable glucose infusion. Samples for glucose radioactivity were measured during the control period and during the last 40 minutes of each step of the euglycemic clamp after establishment of a steady state.

Results: No differences in baseline glucose or insulin levels were detected in any of the study groups as compared with control. Glucose utilization as assessed by the hyperglycemic clamp model was not significantly different from control in the estradiol group, the progesterone group, or the group treated with the combination. In all of the treatment groups, no significant differences were noted under euglycemic, hyperinsulinemic conditions in glucose utilization, hepatic glucoseproduction, or insulin sensitivity.

Conclusions: Women of reproductive age do not demonstrate significant differences in basal levels of glucose or insulin when given a short course of micronized estradiol and progesterone, either alone or in combination. Under conditions of the hyperglycemic, hyperinsulinemic clamp, the pancreatic ß-cell response to hyperglycemia and glucose utilization is not significantly altered by exogenous administration of hormones. Conditions of the euglycemic, hyperinsulinemic clamp failed to elicit significant differences in glucose utilization and insulin sensitivity in any of the three treatment groups. These findings demonstrate that glucosehomeostasis is not altered by the exogenous administration of natural hormones in reproductive-age women.

Key Words: Estradiol • progesterone • hyperglycemic clamp • euglycemic clamp • glucose utilization • insulin sensitivity

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