INS and benign prostatic hyperplasia: In particular, the inhibitory effect of metformin on BPH is due to the down-regulation of the IGF-1 signaling pathway that shares similar biosynthetic sequences with insulin, which is key in prostatic epithelial cell growth, and regulating the stromal-epithelial interaction through the paracrine pathway between IGF-1 and IGF-1 receptor in the prostate [18, 30].