Differential Effects of Raloxifene and Estrogen on Body Composition in Growth Hormone-Replaced Hypopituitary Women

Context: GH deficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuated more markedly by raloxifene, a selective estrogen receptor modulator, compared with 17 beta-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown. Objective: Our objective was to compare the effects of 17 beta-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement. Design: This was an open-label randomized crossover study. Patients and intervention: Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17 beta-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months; the other received the reversed sequence. Main Outcome Measures: Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects. Results: GH therapy significantly increased mean IGF-I during 17 beta-estradiol and raloxifene cotreatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17 beta-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene. Conclusions: In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17 beta-estradiol. Raloxifene has no metabolic advantage over 17 beta-estradiol during GH replacement. (J Clin Endocrinol Metab 97: 1005-1012, 2012)