Morning versus evening administration of estradiol to girls with turner syndrome receiving growth hormone: impact on growth hormone and metabolism. A randomized placebo-controlled crossover study.
Timing of 17beta-estradiol (E2) administration in relation to that of GH could influence the "first pass effect" of E2 on hepatic IGF-I secretion. In order to test this hypothesis, a randomized double-blind placebo-controlled crossover study was conducted. Nine Turner girls (12.8-20.0y) were treated for 2 mo periods with GH 0.1 IU/kg/d sc at bedtime, and oral E2 6-11 microg/kg/d in the morning and placebo in the evening in one 2-mo period and vice versa in the other period. After each period, 24-h blood sampling was performed. IGF-I and mean 24-h integrated GH were comparable. However, the IGF-I/IGFBP-3 ratio was higher (p = 0.05) and insulin levels were lower after evening administration of E2 (24 h: p = 0.03). During an oral glucose tolerance test in the morning, glucagon and insulin were lower following evening E2 administration (ANOVA: glucagon, p = 0.03; insulin, p = 0.04), as well as insulin resistance tended to be lower (p = 0.09).


CONCLUSIONS
The timing of oral E2 supplementation modulates the IGF-I/IGFBP-3 ratio, insulin and glucagon levels in Turner syndrome during GH treatment, Evening administration of oral estrogen together with evening injections of GH may be preferable.
Naeraa
R W
RW
Medical Department M (Endocrinology and Diabetes), Arhus Kommunehospital, Arhus University Hospital, Denmark. rw.naeraa@dadlnet.dk
Gravholt
C H
CH
Kastrup
K W
KW
Svenstrup
B
B
Christiansen
J S
JS
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001774:Blood Chemical Analysis; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014424:Turner Syndrome / Q000188:drug therapy* / Q000378:metabolism
D018972:Insulin-Like Growth Factor Binding Protein 3; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone