Comparison of the metabolic effects of raloxifene and oral estrogen in postmenopausal and growth hormone-deficient women.

• CONTEXT: The endocrine and metabolic functions of the liver are affected by estrogen. Oral estrogen reduces IGF-I and suppresses fat oxidation despite augmenting GH secretion. The aim of this study was to determine whether selective estrogen receptor modulators display similar effects and whether these effects are magnified in GH-deficient (GHD) women because of the loss of GH feedback. DESIGN: This was an open-label, randomized, two-period, crossover study comparing treatment (raloxifene vs. estradiol) and group (normal vs. GHD). SETTING: The setting of this study was a clinical research unit. PARTICIPANTS: Twelve postmenopausal women and 12 women with hypopituitarism participated in this study. INTERVENTION: Two 4-wk treatments with 17beta-estradiol (E2; 2 mg, followed by 4 mg) or raloxifene (60 mg, followed by 120 mg) were given, crossing over to the alternate treatment after a 4-wk washout period. OUTCOME MEASURES: Endocrine [GH, IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein, and SHBG] and metabolic (fat oxidation) end points were used as outcome measures. RESULTS: E2 reduced serum IGF-I levels in a dose-dependent manner in both groups, with effects greater (P < 0.05) than raloxifene. Raloxifene reduced IGF-I levels in the GHD group (P < 0.001), but not in the postmenopausal group. E2 reduced (P < 0.05), and raloxifene increased (P < 0.05), IGFBP-3 levels in both groups. E2, but not raloxifene, increased GH (P < 0.05) in postmenopausal women. The effects of E2 and raloxifene on IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, GH-binding protein, and SHBG were significantly different (P < 0.05). E2 and raloxifene reduced (P < 0.05) fat oxidation equally in GHD, whereas the decrease in postmenopausal women was not significant. CONCLUSION: E2 and raloxifene exert different hepatic endocrine, but not lipid oxidative, effects. The greater effects seen in GHD women may be explained by the loss of endogenous GH feedback.

Keyword

Adolescent

Adult

Cross-Over Studies

Energy Metabolism

drug effects

Estradiol

pharmacology

Female

Human Growth Hormone

blood

deficiency

Humans

Insulin-Like Growth Factor Binding Protein 3

blood

Insulin-Like Growth Factor I

analysis

Lipid Metabolism

Middle Aged

Oxidation-Reduction

Postmenopause

metabolism

Raloxifene

pharmacology

Sex Hormone-Binding Globulin

analysis

Publication and Content Type

ref (subject category)

art (subject category)