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

Area of Science:

• Endocrinology
• Urology
• Prostate Health

Background:

• Benign prostatic hyperplasia (BPH) is often linked to dihydrotestosterone (DHT), but the role of estradiol (E2) and its interaction with androgens is not fully understood.
• Investigating the local steroid microenvironment in the prostate transition zone is crucial for understanding BPH pathogenesis.

Purpose of the Study:

• To determine if transition zone (TZ) tissue concentrations of estradiol (E2), testosterone, and dihydrotestosterone (DHT) are associated with prostate enlargement.
• To explore the relationship between local steroid accumulation and the progression of benign prostatic hyperplasia (BPH).

Main Methods:

• Collected TZ tissue cores from 80 men undergoing prostate biopsy.
• Stratified patients into small (<30 mL) and enlarged (≥30 mL) total prostate volume (TPV) groups.
• Quantified steroid concentrations using liquid chromatography-high resolution mass spectrometry.

Main Results:

• Tissue concentrations of E2, testosterone, and DHT were significantly higher in enlarged prostates compared to smaller ones (p < 0.05).
• Total prostate volume (TPV) showed strong positive correlations with DHT (R=0.870), E2 (R=0.845), and testosterone (R=0.817) across the cohort (p < 0.001).

Conclusions:

• Local accumulation of E2, testosterone, and DHT is strongly associated with prostate enlargement in BPH.
• Findings support a model where coordinated androgenic and estrogenic activity creates a hormonal microenvironment driving BPH progression.
• Local steroidal hyperfunction may amplify stromal-epithelial signaling, contributing to an enlarged prostate.