EFFECTS OF LOW-DOSES OF TRANSDERMAL 17-BETA-ESTRADIOL ON CARBOHYDRATE-METABOLISM IN POSTMENOPAUSAL WOMEN

The impact of a 3-month continuous administration of transdermal estradiol (E2-TTS 50; 50-mu-g/day) or oral conjugated estrogen (CE; 0.625 mg/day) on glucose and lipid metabolism was investigated in two groups (n = 15/group) of postmenopausal women. Fasting levels of glucose, insulin, and C-peptide; C-peptide/insulin ratio (index of hepatic insulin clearance); and their responses to a 75-g oral glucose tolerance test (OGTT) were evaluated before and after 3 months of continuous estrogen administration. E2-TTS 50 modified carbohydrate metabolism, decreasing fasting insulin levels (P < 0.01) and increasing the pancreatic islet response to glucose challenges, as indicated by an increased integrated value of the C-peptide curve associated with OGTT (P < 0.05). Despite greater C-peptide secretion, integrated peripheral insulin after OGTT was decreased (P < 0.05). The resulting increase in the integrated curve of the molar C-peptide/insulin ratio (P < 0.01) indicated elevated hepatic insulin clearance after E2-TTS 50 administration. CE treatment did not modify carbohydrate metabolism, except for reducing fasting glucose levels (P < 0.01). Neither therapy modified lipid metabolism, but a slight increase in circulating triglycerides (P < 0.01) was observed during CE administration. Our data show that the addition of low doses of natural estrogens does not negatively influence glucose and lipid metabolism in postmenopausal women. By contrast, reversal of postmenopausal hypoestrogenism to early follicular phase estrogenic values with E2-TTS 50 administration seems to exert a beneficial effect on glucose metabolism by increasing hepatic insulin clearance.