Context: The endocrine and metabolic function of the liver is affected by estrogen. Oral estrogen reduces IGF-I and suppresses fat oxidation (Fox) despite augmenting GH secretion. Aim: 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: Open label randomized two-period cross over study comparing treatment (raloxifene vs. estradiol) and group (normal vs. GHD)

Setting: Clinical research unit

Participants: Twelve postmenopausal women and 12 women with hypopituitarism

Intervention: Two 4-week treatments with 17 estradiol (E2) (2 mg followed by 4 mg), or raloxifene (60 mg followed by 120 mg), crossing to the alternate treatment after a 4-week washout.

Outcome measures: Endocrine (GH, IGF-I, IGFBP-3, GHBP, SHBG) and metabolic (Fox) endpoints.

Results: E2 reduced serum IGF-I levels in a dose-dependant manner in both groups with the effects greater (P < 0.05) than raloxifene. Raloxifene reduced IGF-I levels in the GHD (P < 0.001) but not in the postmenopausal group. E2 reduced P < 0.05) while 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 between E2 and raloxifene on IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, GHBP and SHBG were significantly different (P < 0.05). E2 and raloxifene reduced (P < 0.05) Fox equally in GHD while the fall 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 loss of endogenous GH feedback.