Effects of conjugated equine estrogen vs. raloxifene on serum insulin-like growth factor-i and insulin-like growth factor binding protein-3: A 2-year, double-blind, placebo-controlled study

Abstract

Objective To assess and compare the effect of conjugated estrogen and of the selective estrogen receptor modulator raloxifene on serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and on the IGF-I/IGFBP-3 ratio. Design A 2-year randomized, double-blind, placebo-controlled study. Setting Endocrinology outpatient department. Patient(s) Fifty-six postmenopausal, hysterectomized women. Intervention(s) Women received raloxifene hydrochloride in doses of 60 mg/day (n = 15) or 150 mg/day (n = 13), conjugated equine estrogen (CEE) in doses of 0.625 mg/day (n = 15), or a placebo (n = 13) over the course of 2 years. Main outcome measure(s) At baseline and after 6, 12, and 24 months of treatment, serum levels of IGF-I, IGFBP-3, and insulin were measured, and an IGF-I/IFGBP-3 ratio was calculated. Result(s) Both raloxifene and CEE decreased serum IGF-I concentration. In contrast to CEE, which had no effect, both raloxifene doses of 60 and 150 mg/day significantly increased serum IGFBP-3 during the 2 years. Compared with placebo, the decrease in IGF-I/IGFBP-3 ratio was −32.5% (95% CI: −20.1; −44.8%) for CEE; −16.4% (95% CI: −3.6; −29.2%) for raloxifene at 150 mg/day; and −15.4% (95% CI: −1.0; −29.8%) for raloxifene at 60 mg/day. No effect of CEE or raloxifene was found on insulin concentration at any time point. Conclusion(s) Long-term use of both CEE and raloxifene decreases serum IGF-I and the IGF-I/IGFBP-3 ratio, but, unlike CEE, raloxifene produced a significant yet small increase in IGFBP-3.