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

Abstract

Objective: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. Design: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 mg/day estradiol for 24 weeks. After 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 sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) 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 concentrations were assessed at baseline and at 12 and 24 weeks of treatment. Results: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. 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 significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (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 normoinsulinemic patients. Conclusions: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.

Effects of tibolone and cyclic hormone replacement therapy on glucose metabolism in non-diabetic obese postmenopausal women: a randomized study

“…In only one study has detailed evaluation of insulin sensitivity when combining cyclic dydrogesterone with oestradiol been reported. In that study, 6 months of ED treatment ameliorated insulin sensitivity in hyperinsulinaemic postmenopausal women, measured by the hyperinsulinaemic euglycaemic clamp, but showed neutral effects in normoinsulinaemic postmenopausal women (44). In our study, the women treated with this combination, albeit obese, were not as hyperinsulinaemic as the women in the study by Cucinelli et al (44) and showed no change in insulin sensitivity during 12 months of treatment.…”

Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction

“…Nevertheless, smaller differences in CIMT between controls and women with PCOS may have been overlooked. Secondly, dydrogesterone given to induce withdrawn bleedings could more or less affect insulin secretion in PCOS patients (41). Nevertheless, in our patients, dydrogesterone was given for a maximum of 5-10 days, whereas in all demonstrations performed in postmenopausal women, hormone replacement therapy was administered for at least 3 months.…”

Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women’s Health Initiative Hormone Trial

“…Other experimental and observational studies failed to find significant differences in glucose levels between hormone therapy users and non-users [7,9,14,16,17,18,19,20,35,36,37,38,39,40,41,42,43,44] or found elevated levels of fasting glucose [12,13]. Likewise, some studies have found lower levels of fasting insulin in hormone users [2,4,5,6,7,8,9,33,35,41,43,45], but others have found no change [10,14,16,17,18,19,20,23,34,36,37,42,44].…”