EFFECTS OF DIFFERENT ORAL ESTROGEN FORMULATIONS ON INSULIN-LIKE GROWTH FACTOR-I, GROWTH-HORMONE AND GROWTH-HORMONE BINDING-PROTEIN IN POSTMENOPAUSAL 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 clarity 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 mug), 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 nol changed by transdermal oestrogen, we conclude that the liver is a major source of circulating GHBP and that GHBP is an oestrogen sensitive protein.