Effect of hormone replacement therapy on insulin secretion and insulin sensitivity in postmenopausal diabetic women

The aim of the present study was to evaluate the effect of three different combinations of hormone replacement therapy (HRT) on insulin secretion, peripheral insulin sensitivity, serum lipid levels and parameters of oxidative stress. Seven type II diabetic women of mean age 55.4 +/- 4.7 years, who had been menopausal for an average of 5 years, were enrolled in the study. Phases of insulin secretion--first (FPIS) and second (SPIS)--and the area under the curve (AUC) for insulin secretion were studied during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was determined using the manual euglycemic-hyperinsulinemic clamp technique. Three different HRT combinations were applied consecutively for 3-month periods: estradiol valerate plus cyproterone acetate (Climen); transdermal 17 beta-estradiol (System TTS 50) plus dydrogesterone (Duphaston) 10 mg daily for 10 days a month; oral 17 beta-estradiol plus dydrogesterone (Femoston) for 14 days a month. A group of nine women with normal glucose tolerance (according to World Health Organization criteria during a 75-g oral glucose tolerance test (OGTT)), of mean age 50.1 +/- 8.2 years and mean body mass index 24.60 +/- 2.01 kg/m2, were also studied, and served as a control group. Insulin secretion improved significantly after Climen: FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 50% after Systen TTS 50 + Duphaston; fasting hyperinsulinemia was normalized and total antioxidant capacity of the serum (TAOCS) was significantly raised (p < 0.01). Femoston led to an increase in insulin sensitivity (by 23%) and in TAOCS (p < 0.05), while fasting hyperinsulinemia remained unchanged. HRT should be prescribed in type II diabetic postmenopausal women because of its favorable effect on existing pathophysiological defects. Cyproterone acetate should be preferred in cases with a predominant beta-cell insulin secretion defect, while dydrogesterone in combination with a transdermal estrogen should be recommended in cases with leading insulin resistance.