Effects of different oral oestrogen formulations on insulin‐like growth factor‐I, growth hormone and growth hormone binding protein in post‐menopausal women

OBJECTIVE: Insulin like growth factor-I (IGF-I) levels in post-menopausal women are reduced by oral administration of the synthetic oestrogen ethinyl oestradiol but increased by transdermal delivery of 17 beta-oestradiol. Since these oestrogen types are different, the aim of this study was to clarify whether reduction in IGF-I is a specific effect of ethinyl oestradiol or common to other oral oestrogen formulations. DESIGN: Randomized cross-over study comparing one month of treatment with ethinyl oestradiol (20 micrograms), conjugated equine oestrogen (1.25 mg Premarin) and oestradiol valerate (2 mg). SUBJECTS: Six healthy post-menopausal women, age 60.3 +/- 5.6 years. MEASUREMENTS: Mean 24 hour GH (from hourly sampling), IGF-I, GH binding protein (GHBP), pituitary (LH, FSH) and hepatic function (SHBG and angiotensinogen) were measured. RESULTS: All three oestrogen formulations resulted in a significant reduction in IGF-I levels compared to baseline and significant elevations of GH and GHBP (P < 0.05). The percentage increase in GH during oestrogen treatment was significantly related to the percentage decrease in IGF-I levels (P = 0.04). All three oestrogen formulations resulted in significant suppression of LH and FSH and induction of the hepatic proteins, SHBG and angiotensinogen (P < 0.05). GHBP increased in parallel with other hepatic proteins. CONCLUSIONS: Reduction in IGF-I levels is an intrinsic effect of oral oestrogen therapy and increased GH levels may occur as a result of reduced feedback inhibition by IGF-I. Since GHBP activity is not changed by transdermal oestrogen, we conclude that the liver is a major source of circulating GHBP and that GHBP is an oestrogen sensitive protein.