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

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Abstract
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 β‐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 μ g), 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 & lt; 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.