Enhanced antiproliferative and anti-inflammatory effects of combined metformin, tadalafil, and tamsulosin in a rat model of testosterone-induced benign prostatic hyperplasia.

Abstract

AIMS: Benign prostatic hyperplasia (BPH) is a common condition in aging men, associated with hormonal imbalances, oxidative stress, and inflammation. This study evaluated the effects of metformin, tadalafil, and tamsulosin administered individually or in combination on testosterone-induced BPH. MATERIALS AND METHODS: Following BPH induction, 48 male Wistar rats were divided into six groups: normal control, BPH control, and four treatment groups receiving metformin (500 mg/kg/day), tadalafil (2 mg/kg/day), tamsulosin (10 μg/kg/day), or their combination for two weeks. Serum levels of urea, creatinine, uric acid, reduced glutathione (GSH), and malondialdehyde (MDA) were measured using enzymatic colorimetric assays. Prostate tissue levels of prostate-specific antigen (PSA), estradiol, dihydrotestosterone (DHT), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed via ELISA. mRNA expression of cyclooxygenase-2 (COX-2), transforming growth factor β-2 (TGFβ-2), insulin growth factor-2 (IGF-2), and bone morphogenetic protein 5 (BMP5) was assessed by quantitative real-time PCR. KEY FINDINGS: Histopathological examination confirmed BPH induction through increased prostate weight and prostate index. While monotherapies alleviated BPH-related changes, com-bination therapy showed superior antioxidant activity and significantly improved kidney function markers. It also markedly reduced PSA, estradiol, and DHT levels, along with significant downregulation of COX-2, TGFβ-2, IGF-2, BMP5, NF-κB, and TNF-α. SIGNIFICANCE: although individual treatments provided benefits, their combined use enhanced therapeutic outcomes through modulation of oxidative stress, inflammation, and androgenic activity in BPH management.