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, I² = 0.0%) decreased IGF-1 levels more than 60 mg/day (WMD: −2.29 ng/mL, 95% CI: −2.90 to −1.69, I² = 16%). Moreover, intervention duration ˃26 weeks (WMD: −3.48 ng/mL, 95% CI: −5.26 to −1.69, I² = 0.0%) reduced IGF-1 levels more than ˂26 weeks (WMD: −2.55 ng/mL, 95% CI: −3.31 to −1.79, I² = 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.