Elevated Estradiol and DHT Levels in the Prostatic Stroma as Key Drivers of Benign Prostatic Hyperplasia Pathogenesis

While dihydrotestosterone (DHT) has traditionally been considered the principal steroid in benign prostatic hyperplasia (BPH) pathogenesis, the role of estradiol (E2) and its relationship with local androgen accumulation remain unclear. This study investigated whether transition zone (TZ) tissue concentrations of E2, testosterone, and DHT are associated with prostate enlargement. TZ tissue cores were collected from 80 men undergoing prostate biopsy. Patients were stratified by total prostate volume (TPV): small (<30 mL) and enlarged (≥30 mL) prostate groups. Steroids were quantified using liquid chromatography-high resolution mass spectrometry. Tissue concentrations of E2, testosterone, and DHT were significantly higher in enlarged prostates (E2: 0.031 vs. 0.012 ng/g; testosterone: 0.804 vs. 0.517 ng/g; DHT: 7.903 vs. 3.526 ng/g; all p < 0.05). Across the cohort, TPV strongly correlated with DHT (R = 0.870, p < 0.001), E2 (R = 0.845, p < 0.001), and testosterone (R = 0.817, p < 0.001). These findings demonstrate a strong association between local steroid accumulation and prostate enlargement, supporting the hypothesis that coordinated androgenic and estrogenic activity shapes the hormonal microenvironment driving BPH progression. This pattern aligns with a model of local steroidal hyperfunction that may amplify stromal-epithelial signaling in the enlarged prostate.