Modulatory Effect of Raloxifene and Estrogen on the Metabolic Action of Growth Hormone in Hypopituitary Women

Vita Birzniece, Udo Meinhardt, James Gibney, Gudmundur Johannsson, Robert C. Baxter, Markus J. Seibel, and Ken K. Y. Ho*

Garvan Institute of Medical Research and Department of Endocrinology (V.B., U.M., J.G., G.J., K.K.Y.H.), St. Vincent's Hospital, Sydney, NSW 2010, Australia; The University of New South Wales (K.K.Y.H.), Sydney, NSW 2052, Australia; Kolling Institute of Medical Research (R.C.B.), The University of Sydney, Royal North Shore Hospital, Sydney, NSW 2065 Australia; and ANZAC Research Institute (M.J.S.), The University of Sydney at Concord, NSW 2139, Australia

* To whom correspondence should be addressed. E-mail: k.ho@garvan.org.au.

Context: The metabolic action of GH is attenuated by estrogens administered via the oral route. Selective estrogen receptor modulators lower IGF-I to a lesser degree than 17β-estradiol in GH-deficient women, and their effect on fat and protein metabolism is unknown.

Objective: The aim of the study was to compare the modulatory effects of 17β-estradiol and raloxifene, a selective estrogen receptor modulator, on the metabolic action of GH. Design: We conducted an open-label, two-group, randomized, two-period crossover study.

Patients and Intervention: Ten hypopituitary women received GH therapy alone (0.5 mg/d) and GH plus 17β-estradiol (E₂; 2 mg/d). Eleven hypopituitary women received GH therapy alone and GH plus raloxifene (R; 60 mg/d). The treatment duration was 1 month, with a 4-wk washout period.

Main Outcome Measures: IGF-I, IGFBP-3, resting energy expenditure, and fat oxidation were quantified by indirect calorimetry. We measured whole body leucine turnover from which leucine rate of appearance and leucine incorporation into protein were estimated.

Results: GH significantly stimulated all outcome measures. During GH treatment, addition of R significantly reduced mean IGF-I but not IGFBP-3, whereas E₂ reduced both IGF-I and IGFBP-3 levels. Cotreatment with R but not E₂ significantly attenuated the stimulatory effects of GH on fat oxidation. There was a strong trend (P = 0.08) toward a greater reduction in leucine incorporation into protein after R compared to E₂ cotreatment.

Conclusions: The modulatory effects of E₂ and R at therapeutic doses on GH action are different. R during GH therapy exerts a greater inhibitory effect on lipid oxidation and protein anabolism compared to E₂

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-2743v1