Intravenous estrogens increase insulin clearance and action in postmenopausal women

Abstract

To test the hypothesis that estrogens alter insulin action, we evaluated the effects of intravenous conjugated estrogens (CE) on insulin-stimulated steady-state glucose infusion rate (SSGIR) and suppression of plasma glycerol in postmenopausal women (mean +/- SD; 56 +/- 4 yr; n = 12) not using hormone replacement. SSGIR and glycerol were measured during a two-stage (8 and 40 mU. m-2. min-1) hyperinsulinemic euglycemic clamp on 2 days, with or without a 2.5-mg intravenous CE bolus. Serum estradiol concentrations were increased approximately 200% on the estrogen (EST) compared with the control (CON) days. Serum insulin was reduced (P < 0.01) during stage 2 of the clamp for EST (63.3 +/- 12.8 micro U/ml) vs. CON (78.2 +/- 15.8 micro U/ml). Mean SSGIR and plasma glycerol did not differ between CON and EST days. With adjustment for differences in insulin concentration between conditions, stage 2 glucose disposals were significantly higher (8.63 vs. 7.20 mg. kg-1. min-1) and plasma glycerol concentrations were significantly lower (29.4 vs. 35.0 micro mol/l) for EST vs. CON. Our findings suggest that acute CE administration increases insulin clearance and action in postmenopausal women.

Fig. 1

Two-stage hyperinsulinemic euglycemic clamp procedure. CE, conjugated estrogens; IIR, insulin infusion rate; GIR, glucose infusion rate. Blood samples were obtained at time 0, and at 60, 75, and 90 min during baseline, stage 1, and stage 2.

Fig. 2

Mean (±SD) GIR (A) and glycerol concentrations (B) during stage 1 (100–190 min; 8 mU· m⁻² · min⁻¹) and stage 2 (200–290 min; 40 mU· m⁻² · min⁻¹) of the hyperinsulinemic euglycemic clamp. Steady-state levels for GIR (SSGIR) and glycerol concentrations at the end of each stage were not significantly different on the estrogen (EST, ○) and control (CON, •) days.

Fig. 3

Mean (±SE) insulin-stimulated SSGIR (A) and glycerol concentrations (B) during the final 30 min of each insulin clamp stage on the estrogen (EST, Δ) and control (CON, •) days. Stage 2 serum insulin concentrations were lower on the EST day than on the CON day. After differences in stage 2 insulin concentrations were controlled for, there were significant (*P < 0.05) main effects of estrogen on SSGIR and glycerol.