# Estrogen regulation in the prostate underlies racial disparity in men with benign prostatic hyperplasia

## TL;DR

The study explores how estrogen regulation in the prostate differs between African American and European American men, contributing to racial disparities in benign prostatic hyperplasia.

## Contribution

The study identifies racial differences in estrogen receptor regulation and steroid metabolism in benign prostate tissues, offering insights for precision therapies.

## Key findings

- Steroid metabolism gene expression differs between normal African American and European American prostates.
- ERα's role in LUTS/BPH is more pronounced in European American samples, while African American samples show increased ER and metabolism gene expression.
- Collagen deposition does not significantly differ between racial groups in LUTS/BPH prostate tissues.

## Abstract

Lower urinary tract symptoms (LUTS), associated with benign prostatic hyperplasia (BPH), are an aging‐related disease, with more than 210 million cases worldwide. Estrogen exposure and estrogen regulation have been implicated in a variety of disease processes, with estrogen receptor (ER)‐α pathways associated with disease progression and ERβ pathways considered to be disease‐protective through enhanced apoptosis and reduced cellular proliferation. Preclinical models of LUTS/BPH have shown that ERα activation contributes to disease initiation and progression. Self‐identified African American (AA) men have a high incidence of LUTS/BPH, with increased incidence of non‐surgical treatment failure, larger prostates at time of surgery, and surgery occurring at a younger age compared with self‐identified European American (EA) men. While circulating estrogen levels are higher in AA individuals, regulation of ERs, particularly ERβ, in normal and LUTS/BPH human prostate has not been well characterized. In this study, we examined differences in ER expression between peripheral zone (PZ) and transition zone (TZ) prostate tissues using multiplex, multispectral imaging. Additionally, we assessed changes in ERs and steroid metabolism genes involved in ERβ signaling between normal and LUTS/BPH prostate samples. Our study revealed underlying differences in steroid metabolism gene expression between normal AA and EA prostates, which were further altered with LUTS/BPH. Importantly, the contribution of ERα to LUTS/BPH was more pronounced in EA prostate samples, whereas AA prostate samples exhibited an overall increase in the expression of both ER and estrogen metabolism‐related genes. Although estrogens have also been implicated in collagen deposition in the prostate of LUTS/BPH patients, we did not observe significant differences in collagen deposition between AA and EA samples. These results suggest that racial differences in steroid hormone signaling pathways within the benign prostate represent a promising area for the development of precision‐based therapies to reduce LUTS in aging men. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.