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.
This was a randomized, multicenter, double-blind, double-dummy trial. Postmenopausal women were randomized to receive either daily intranasal E2/NET (175 μg/275 μg) 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.
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).
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.
Oral estrogen therapy suppresses IGF-I levels whereas conventional dose transdermal estradiol does not. It has been proposed that if sufficiently high serum estradiol levels are achieved, non oral estradiol will also suppress serum IGF-I. In this study, intranasal estradiol at a dose that results in serum levels that exceed the proposed threshold for GH and IGF-I effects did not alter IGF-I levels. This suggests that the effect of exogenous estrogen on IGF-1 is a function of the method of administration rather than being dose related.
From the 1Women's Health Program, Department of Medicine, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia; 2Keogh Institute for Medical Research, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, School of Medicine and Pharmacology, University of Western Australia, WA, Australia; and 3Adelaide Hormone and Menopause Centre, Research Centre for Reproductive Health, University of Adelaide, SA, Australia.
Received February 24, 2008; revised and accepted March 17, 2008.
Financial disclosure: None reported.
Address correspondence to: Susan Davis, MD, PhD, Women's Health Program, Department of Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Commercial Road, Prahran, VIC 3181, Australia. E-mail: email@example.com