Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women

OBJECTIVE Menopause diminishes insulin secretion and elimination, increases risk of diabetes and adversely affects lipoprotein metabolism. This study was undertaken to establish whether oral oestradiol plus dydrogesterone postmenopausal hormone therapy can modify these changes. DESIGN Randomized prospective trial of postmenopausal women taking low dose therapy (1 mg/day oestradiol-17 beta with 5 or 10 mg/day dydrogesterone for days 17-28 of each cycle, n = 15) or high dose therapy (2 mg/day oestradiol-17 beta with 10 or 20 mg/day orally administered dydrogesterone, n = 9). MEASUREMENTS Patients underwent measurement of glucose, insulin and C-peptide in the fasting state and during an intravenous glucose tolerance test (IVGTT) at baseline and after 12 and 24 cycles of treatment. Modelling analysis was used to derive measures of insulin secretion, elimination and sensitivity. Fasting serum lipids, lipoproteins and apolipoproteins were also measured. RESULTS In both groups there were significant reductions in fasting glucose, insulin and C-peptide. Pancreatic insulin secretion during the IVGTT was increased by treatment (ranging from 45% to 92%, P < 0.01). Insulin elimination was increased at both the peripheral (16% to 43%, P < 0.05) and hepatic (18% to 31%, P < 0.05) levels. Insulin sensitivity was unaffected. Low density lipoprotein (LDL) cholesterol was reduced and high density lipoprotein (HDL) cholesterol increased with treatment. CONCLUSIONS Postmenopausal hormone therapy with oestradiol plus dydrogesterone can favourably affect lipoprotein concentrations and can reverse menopause-associated changes in insulin secretion and elimination.