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 glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration.


METHODS
The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta-oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double-blind, double-dummy study for six months.


METHODS
Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group.


METHODS
Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT.


RESULTS
A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased 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 the changes in glucose metabolism.


CONCLUSIONS
Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.
Karjalainen
A
A
Department of Internal Medicine, University of Oulu, Oulu, Finland. anna.h.karjalainen@oulu.fi
Paassilta
M
M
Heikkinen
J
J
Bäckström
A C
AC
Savolainen
M
M
Kesäniemi
Y A
YA
D000279:Administration, Cutaneous; D000284:Administration, Oral; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D015914:Estrogen Replacement Therapy; D005260:Female; D005782:Gels; D005951:Glucose Tolerance Test; D006801:Humans; D007044:Hysterectomy; D007328:Insulin / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D002096:C-Peptide; D005782:Gels; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D004958:Estradiol; D007334:Insulin-Like Growth Factor I