Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism

OBJECTIVE Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glyc osylated haemoglobin GHbA(1c) have been studied only among diabetics. The o bjective of this studywas to evaluate the effects on glucose and insulin me tabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta -oestradiol gel (1 mg oestra diol/day) and placebo tablets in a randomised, double-blind, double-dummy s tudy for six months. PATIENTS Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IG FBP-1 were measured at baseline and after six months of therapy. In additio n, insulin sensitivity and insulin secretion indices were obtained from OGT T. RESULTS A small significant reduction in the GHbA(1c) concentration was obs erved during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The respons e to a standard 75 g oral glucose load was similar in the study groups. Com pared with the baseline values, the area under the curve for C-peptide decr eased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with t he changes in glucose metabolism. CONCLUSIONS Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time per iod of 6 months.