Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion

Objective: To evaluate the impact on glucose and insulin metabolism of tran sdermal estrogen patches before and after the addition of cyclic dydrogeste rone in postmenopausal women. Design: We studied 21 postmenopausal women seeking treatment for symptomati c menopause. All patients received transdermal 50 mu g/day estradiol for 24 weeks. lifter 12 weeks of treatment, 10 mg/day dydrogesterone were added, Methods: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT), insulin sensiti vity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insuli n and C-peptide response to OGTT were expressed as area under the curve (AU C) and as incremental AUC; insulin sensitivity was expressed as mg/kg; body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentr ations were assessed at baseline and at 12 and 24 weeks of treatment. Results: Nine patients proved to be hyperinsulinemic and 12 were normoinsul inemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients : addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a s ignificant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoi nsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsuli nemic patients, Conclusions: Transdermal estrogen substitution alone and combined with cycl ical dydrogesterone may ameliorate hyperinsulinemia in a selected populatio n, of postmenopausal women.