# Exploring Sulpiride as an Alternative to Testosterone Propionate for Inducing Benign Prostatic Hyperplasia in Rodent Models

## TL;DR

This paper compares two methods for inducing benign prostatic hyperplasia in rodents, finding that sulpiride is a more accessible and clinically relevant alternative to testosterone propionate.

## Contribution

The study evaluates and recommends sulpiride as a practical and human-relevant alternative to testosterone propionate for BPH research in rodent models.

## Key findings

- Sulpiride induces BPH via hyperprolactinemia and affects lateral and dorsal prostate lobes.
- Testosterone propionate requires castration and induces epithelial hyperplasia in ventral lobes.
- Sulpiride is non-invasive, readily available, and mimics human BPH pathogenesis better.

## Abstract

Benign prostatic hyperplasia (BPH) is a significant health issue among ageing men, with ongoing research focused on elucidating its underlying mechanisms and improving experimental models. Testosterone Propionate (TP) is the first line of choice for the induction of BPH in experimental rodent models. However, TP’s controlled status as a Schedule III drug in the United States and a Class C drug in the UK presents challenges in obtaining TP for experimental use, giving preference to the sulpiride model since it is easily obtained as an alternative for the induction and study of BPH. A comprehensive literature search was conducted across multiple electronic databases, including PubMed/MEDLINE, Embase, and Web of Science. The primary PubMed search strategy included combinations of Medical Subject Headings (MeSH) and free-text terms: (“Benign prostatic hyperplasia induction” OR “and rodent models’’) AND (“Testosterone Propionate model”) AND (“sulpiride model”). Studies were included if they induced BPH (using testosterone or sulpiride models). Titles and abstracts were screened for relevance; eligible articles underwent full-text review, with data extracted thematically. No formal risk-of-bias scoring was used due to the narrative approach; instead, studies were appraised by design, rigor, plausibility, and evidence. This study reviewed published and publicly available data, so no ethical approval was required. Although both TP and sulpiride induce BPH via various mechanisms, this review provides a comparative analysis of these two commonly utilised models for studying BPH. In the TP approach, castrated rodents receive daily subcutaneous injections for 4 weeks, resulting in dihydrotestosterone (DHT)-mediated epithelial hyperplasia predominantly affecting the ventral prostate lobes. Conversely, the sulpiride model is non-invasive, employs intact animals treated with sulpiride, and induces hyperprolactinemia-mediated BPH via interactions with androgen and oestrogen receptor pathways that stimulate prostatic stromal and epithelial proliferation, particularly in the lateral and dorsal lobes, representing an alternative method. We also highlight the strengths and limitations of TP and sulpiride in replicating clinical symptoms and examine the toxicological effects of sulpiride on the kidney, testis, liver, and brain. We recommend the sulpiride model for the induction and studying of BPH, as it is readily accessible and closely mimics the pathogenesis of BPH in humans, unlike the TP model, which requires castration.