Long-term effects of oral estradiol and dydrogesterone on carbohydrate metabolism in postmenopausal women.

OBJECTIVE To determine in postmenopausal women the long-term effects on carbohydrate metabolism of the administration of oral micronized 17 beta-estradiol (2 mg/day continuously) and cyclical dydrogesterone (10 mg/day for 14 days per 28-day cycle). METHODS A 2-year open-label prospective, non-comparative study was carried out of 13 healthy postmenopausal women receiving cyclical estradiol and dydrogesterone and serving as their own controls. Concentrations of blood glucose, plasma insulin, C-peptide, glucagon and free fatty acids (FFAs) were determined before treatment (base-line) and at 6, 12 and 24 months of hormone replacement therapy under fasting conditions and during a standard 75-g, 3-h, oral glucose tolerance test (OGTT). RESULTS Fasting blood glucose levels were unchanged throughout the study, and the mean areas under the curves (AUCs) for glucose response increased slightly but non-significantly versus baseline; fasting plasma insulin levels tended a decrease, and AUCs for insulin responses to the glucose load fell by 23% from baseline (not significant); fasting C-peptide levels and AUCs were unchanged; plasma glucagon fasting levels and responses were in the normal range and stable throughout the study; and plasma FFA fasting levels decreased significantly, as well as FFA AUCs during OGTTs, at the 12th and 24th months of the study. CONCLUSIONS During a 2-year treatment with oral estradiol and cyclical dydrogesterone, a direct progesterone derivative, tolerance to glucose was unchanged, fasting plasma insulin and insulin response to repeated glucose loads were decreased, and C-peptide levels remained unchanged, indicating a potential improvement in insulin sensitivity and clearance, as in younger women; additionally, a slightly enhanced antilipolytic activity of insulin was observed.