Effects of raloxifene administration on serum levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein 3 levels: A systematic review and meta-analysis of randomized controlled trials

Objective: To ascertain the clinical magnitude of raloxifene administration on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Methods: A systematic comprehensive search was performed without language limitation up to 14 December 2020. We included only trials that assessed the effect of raloxifene on IGF-1 and IGFBP-3 in adults. Meta-analysis was performed using the Stata software (Stata Corp. College Station, Texas, USA). Results: Seven arms were included, encompassing postmenopausal women with type 2 diabetes mellitus, postmenopausal women with breast cancer, healthy postmenopausal women, and healthy elderly men. Raloxifene therapy significantly reduced IGF-1 levels (WMD: -2.92 nmol/L, 95% CI: -3.49, -2.35, p < 0.001) compared to placebo. Raloxifene dosage >60 mg/day (WMD: -3.29 ng/mL, 95% CI: -3.50 to -3.08, I-2 = 0.0%) decreased IGF-1 levels more than 60 mg/day (WMD: -2.29 ng/mL, 95% CI: -2.90 to -1.69, I-2 = 16%). Moreover, intervention duration >26 weeks (WMD: -3.48 ng/mL, 95% CI: -5.26 to -1.69, I-2 = 0.0%) reduced IGF-1 levels more than <26 weeks (WMD: -2.55 ng/mL, 95% CI: -3.31 to -1.79, I-2 = 92%). In contrast, overall results from the random-effects model did not suggest a significant change in IGFBP-3 levels upon raloxifene therapy. Conclusion: Raloxifene therapy significantly reduced serum levels of IGF-1 levels but without changes in IGFPB-3 levels.