Phosphodiesterase inhibitors for the management of lower urinary tract symptoms in men without benign prostatic hyperplasia: a systematic review

Background: Lower urinary tract symptoms (LUTS) are common in men and can lead to impaired quality of life. While phosphodiesterase type 5 inhibitors (PDE5-Is) are established in managing LUTS related to benign prostatic hyperplasia (BPH), their role in non-BPH male LUTS remains unclear. This systematic review aimed to evaluate the efficacy and safety of PDE5-Is in men with LUTS unrelated to prostate enlargement. Methods: A systematic search of four databases (PubMed, Web of Science, ScienceDirect, and EBSCO) identified five eligible clinical trials that enrolled men with LUTS secondary to non-BPH etiologies such as post-prostate brachytherapy, overactive bladder (OAB), and double-J (DJ) ureteral stents. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB-2) tool for randomized trials and the Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool for non-randomized trials. Data were synthesized descriptively due to heterogeneity and limited number of studies. Our review was registered in advance in PROSPERO (CRD420251072896). Results: From 341 identified studies, 5 clinical trials met the inclusion criteria. Interventions included tadalafil, sildenafil, and combination regimens with tamsulosin or solifenacin. PDE5-Is consistently improved urinary symptoms, International Prostate Symptom Score (IPSS) reduction, pain, storage and voiding scores, and sexual function. Tadalafil showed the most consistent benefits, particularly in sexual health and pain relief, while combination therapy (tamsulosin + solifenacin or sildenafil) yielded broader urinary symptom improvement. Objective measures such as the maximum urinary flow rate (Qmax) and post-void residual (PVR) improved modestly but less consistently. This review is limited by the small number of studies and the heterogeneity of participants among the included studies. Conclusions: PDE5-Is, especially tadalafil, are effective and well-tolerated for non-BPH LUTS in men, offering advantages beyond urinary symptom relief, including sexual function preservation and pain reduction. These potential effects should be further explored, particularly when erectile dysfunction (ED) or discomfort is present.