A COMPARISON OF THE EFFECTS OF ORAL AND TRANSDERMAL ESTROGEN REPLACEMENT ON INSULIN SENSITIVITY IN POSTMENOPAUSAL WOMEN

Previous studies have shown that oral, but not transdermal, administra tion of estrogen stimulates GH secretion in postmenopausal women. Beca use GH impairs insulin action, the impact of estrogen replacement ther apy on carbohydrate metabolism may be influenced by the route of admin istration. The aim of this study was to prospectively compare the effe cts of oral and transdermal estrogen replacement on glucose tolerance and insulin sensitivity in postmenopausal women. In an open label, ran domized, cross-over study, nine postmenopausal women were randomized t o transdermal estrogen patches (Estraderm-TTS 100) or oral conjugated estrogen (Premarin, 1.25 mg) daily for 12 weeks and then crossed over to receive the alternative treatment for a further 12 weeks. An oral g lucose tolerance test and hyperinsulinemic euglycemic clamp (HEC) were per formed before treatment and at the end of 10 weeks of treatment. Oral and transdermal estrogen both significantly reduced LH to the sam e degree. Mean GH did not significantly change with transdermal estrog en, but rose significantly during oral estrogen therapy. Peak and mean glucose and insulin levels during the oral glucose tolerance test wer e not altered by estrogen therapy and were not significantly different between treatments. Mean glucose and insulin levels were maintained a t an identical level during the HEC performed at pretreatment and duri ng estrogen therapy. The mean glucose infusion rate required to mainta in euglycemia during the HEC (mean +/- SEM, pretreatment, 40.4 +/- 4.8 mu mol/kg . min) was unaltered by oral (39.8 +/- 4.6 mu mol/kg . min) or transdermal estrogen treatment (42.1 +/- 4.2 mu mol/kg . min). How ever, during the transdermal estrogen phase (60 +/- 10 mu mol/L), the mean nonesterified free fatty acid concentration was suppressed to a s ignificantly lower level during the HEC than during the oral estrogen phase(120 +/- 20 mu mol/L; P < 0.05). We conclude that compared to the oral route, transdermal estrogen therapy is associated with a slight, but significant, improvement of insulin action on lipid metabolism. H owever, in the short term, the route of estrogen replacement therapy d oes not have a major impact on glucose metabolism in postmenopausal wo men.