Context: Data from large clinical trials of postmenopausal women suggest that the incidence of diabetes is reduced in women randomized to estrogen-based hormone therapy when compared with placebo. Whether this is due to an effect of estrogen on insulin or glucose metabolism remains unclear.
Objective: Our objective was to test the hypothesis that estradiol (E(2)) increases insulin secretion and clearance.
Design: Serum insulin and C-peptide (CPEP) responses to hyperglycemia (250 mg/dl) plus iv L-arginine were measured on 2 separate days, with (EST) and without [control (CON)] subacute (24 h) transdermal E(2) administration.
Study participants: There were 11 postmenopausal women (mean +/- sd; 55 +/- 4 yr) included in this study.
Main outcomes: Insulin secretion and clearance were estimated from the CPEP area under the curve and the molar ratio of CPEP to insulin area under the curve, respectively. Mean glucose disposal rate (GDR) was estimated from the rate of glucose infusion during the final 30 min of the hyperglycemic clamp.
Results: There were no differences in insulin secretion or clearance between the EST and CON days. Fasting glucose was lower on the EST compared with the CON (93 +/- 6 vs. 98 +/- 8 mg/dl), but mean GDR was not different. However, when one outlier was excluded from analysis, GDR was increased after EST compared with CON. Furthermore, a strong inverse association was observed between years since menopause and E(2)-mediated changes in GDR (r = -0.794; P = 0.004).
Conclusions: Contrary to our hypothesis, 24-h transdermal E(2) administration did not alter insulin secretion or clearance in postmenopausal women. However, a longer time since menopause was associated with a reduced effect of E(2) to increase glucose uptake.