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Effects of the route of estrogen administration on insulinlike growth factor-I, IGF binding protein-3, and insulin resistance in healthy postmenopausal women: results from a randomized, controlled study.
Menopause. 2008 Nov-Dec; 15(6):1065-9.M

Abstract

OBJECTIVE

Oral estrogen therapy suppresses insulin like growth factor I (IGF-I) levels, whereas conventional dose transdermal estradiol (E2) does not. However, it has been proposed that if sufficiently high serum E2 levels are achieved, nonoral E2 will also suppress serum IGF-I. The aim of the study was to investigate the effects of intranasal E2 with norethisterone (E2/NET) versus oral E2/NET acetate on IGF-I, IGF binding protein 3, and insulin resistance in postmenopausal women.

DESIGN

This was a randomized, multicenter, double-blind, double-dummy trial. Postmenopausal women were randomized to receive either daily intranasal E2/NET (175 microg/275 microg) as a spray and a placebo tablet (n = 41) or oral E2/NET acetate (1 mg/0.5 mg) plus placebo intranasal spray (n = 41) for 1 year. Fasting plasma concentrations of IGF-I, IGF binding protein 3, glucose and insulin, glucose and insulin at 120 minutes post-glucose challenge, and the homeostasis model assessment for insulin resistance were assessed at baseline and after 52 weeks of treatment.

RESULTS

The two groups were well matched for all clinical and biochemical parameters at baseline. There were no significant between-group differences for fasting and 120-minute glucose, insulin, homeostasis model assessment for insulin resistance, and IGF binding protein 3. The mean IGF-I level at week 52 was significantly lower for women treated with oral versus intranasal therapy (116 +/- 21 [SD] versus 134 +/- 33 [SD], P = 0.005) and the mean difference in change over 52 weeks in IGF-I was significantly different between groups (-19, 95% CI:-37 to -1, P = 0.04).

CONCLUSIONS

In healthy postmenopausal women, intranasal E2 at a dose that results in serum levels that exceed the proposed threshold for growth hormone and IGF-I effects, does not alter IGF-I levels. This suggests that the effect of exogenous estrogen on IGF-I is a function of the method of administration rather than being dose related.

Authors+Show Affiliations

Women's Health Program, Department of Medicine, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia. susan.davis@med.monash.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

18806686

Citation

Davis, Susan R., et al. "Effects of the Route of Estrogen Administration On Insulinlike Growth factor-I, IGF Binding Protein-3, and Insulin Resistance in Healthy Postmenopausal Women: Results From a Randomized, Controlled Study." Menopause (New York, N.Y.), vol. 15, no. 6, 2008, pp. 1065-9.
Davis SR, Stuckey BG, Norman RJ, et al. Effects of the route of estrogen administration on insulinlike growth factor-I, IGF binding protein-3, and insulin resistance in healthy postmenopausal women: results from a randomized, controlled study. Menopause. 2008;15(6):1065-9.
Davis, S. R., Stuckey, B. G., Norman, R. J., Papalia, M. A., Drillich, A., & Bell, R. J. (2008). Effects of the route of estrogen administration on insulinlike growth factor-I, IGF binding protein-3, and insulin resistance in healthy postmenopausal women: results from a randomized, controlled study. Menopause (New York, N.Y.), 15(6), 1065-9. https://doi.org/10.1097/gme.0b013e318174f16e
Davis SR, et al. Effects of the Route of Estrogen Administration On Insulinlike Growth factor-I, IGF Binding Protein-3, and Insulin Resistance in Healthy Postmenopausal Women: Results From a Randomized, Controlled Study. Menopause. 2008;15(6):1065-9. PubMed PMID: 18806686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the route of estrogen administration on insulinlike growth factor-I, IGF binding protein-3, and insulin resistance in healthy postmenopausal women: results from a randomized, controlled study. AU - Davis,Susan R, AU - Stuckey,Bronwyn G A, AU - Norman,Robert J, AU - Papalia,Mary-Anne, AU - Drillich,Ann, AU - Bell,Robin J, PY - 2008/9/23/pubmed PY - 2009/4/2/medline PY - 2008/9/23/entrez SP - 1065 EP - 9 JF - Menopause (New York, N.Y.) JO - Menopause VL - 15 IS - 6 N2 - OBJECTIVE: Oral estrogen therapy suppresses insulin like growth factor I (IGF-I) levels, whereas conventional dose transdermal estradiol (E2) does not. However, it has been proposed that if sufficiently high serum E2 levels are achieved, nonoral E2 will also suppress serum IGF-I. The aim of the study was to investigate the effects of intranasal E2 with norethisterone (E2/NET) versus oral E2/NET acetate on IGF-I, IGF binding protein 3, and insulin resistance in postmenopausal women. DESIGN: This was a randomized, multicenter, double-blind, double-dummy trial. Postmenopausal women were randomized to receive either daily intranasal E2/NET (175 microg/275 microg) as a spray and a placebo tablet (n = 41) or oral E2/NET acetate (1 mg/0.5 mg) plus placebo intranasal spray (n = 41) for 1 year. Fasting plasma concentrations of IGF-I, IGF binding protein 3, glucose and insulin, glucose and insulin at 120 minutes post-glucose challenge, and the homeostasis model assessment for insulin resistance were assessed at baseline and after 52 weeks of treatment. RESULTS: The two groups were well matched for all clinical and biochemical parameters at baseline. There were no significant between-group differences for fasting and 120-minute glucose, insulin, homeostasis model assessment for insulin resistance, and IGF binding protein 3. The mean IGF-I level at week 52 was significantly lower for women treated with oral versus intranasal therapy (116 +/- 21 [SD] versus 134 +/- 33 [SD], P = 0.005) and the mean difference in change over 52 weeks in IGF-I was significantly different between groups (-19, 95% CI:-37 to -1, P = 0.04). CONCLUSIONS: In healthy postmenopausal women, intranasal E2 at a dose that results in serum levels that exceed the proposed threshold for growth hormone and IGF-I effects, does not alter IGF-I levels. This suggests that the effect of exogenous estrogen on IGF-I is a function of the method of administration rather than being dose related. SN - 1530-0374 UR - https://www.unboundmedicine.com/medline/citation/18806686/Effects_of_the_route_of_estrogen_administration_on_insulinlike_growth_factor_I_IGF_binding_protein_3_and_insulin_resistance_in_healthy_postmenopausal_women:_results_from_a_randomized_controlled_study_ L2 - http://dx.doi.org/10.1097/gme.0b013e318174f16e DB - PRIME DP - Unbound Medicine ER -