SPP1 and benign prostatic hyperplasia: Studies indicate that imbalances in steroid hormones (e.g., testosterone and estradiol) upregulate pro-inflammatory genes Spp1 (encoding osteopontin) and Saa1. Elevated osteopontin exacerbates prostate cell proliferation (56), suggesting that hormone-related factors may occur before inflammation, and that the stimulatory effects of growth factors on prostate cells are initially observable (48), highlighting their dual roles in early BPH pathogenesis.