Efficacy and safety of α-blockers plus 5α-reductase inhibitors for benign prostatic hyperplasia: a systematic review and meta-analysis.

Abstract

Objective: This meta-analysis was conducted to systematically evaluate the efficacy and safety of combination therapy with alpha-adrenergic blockers (α-ABs) and 5α-reductase inhibitors (5α-RIs) for benign prostatic hyperplasia (BPH), providing evidence-based support for clinical decision-making.

Methods: A comprehensive computerized search was performed in PubMed, MEDLINE, Web of Science, Cochrane Library, and EMBASE to identify relevant controlled trials published from database inception to September 2025. Two researchers independently screened the literature, extracted data, and assessed study quality using the Risk of Bias 2.0 (ROB 2.0) tool. Outcome data were extracted, and statistical analysis was performed. The weighted mean difference (WMD) or standardized mean difference (SMD) was calculated for continuous variables, while relative risk (RR) with 95% confidence intervals (CI) was computed for dichotomous variables. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated using funnel plots and Egger's test.

Results: A total of 9 randomized controlled trials involving 13052 BPH patients were included. Meta-analysis demonstrated that, compared with α-AB monotherapy, combination therapy showed significant advantages in reducing the International Prostate Symptom Score (I-PSS) (MD = -0.20, 95% CI -0.26, -0.14), decreasing prostate volume (PV) (MD = -13.69, 95% CI -18.06, -9.32), increasing the maximum urinary flow rate (Qmax) (MD = 0.21, 95% CI 0.13, 0.29), and lowering prostate-specific antigen (PSA) levels (MD = -1.38, 95% CI -1.81, -0.95). In terms of safety, combination therapy significantly reduced the postoperative surgical rate compared with monotherapy (logRR = -1.11,95% CI -1.42, -0.80), and the risk of acute urinary retention (AUR) was lower in the combination therapy group (logRR = -1.08, 95% CI -1.48, -0.68). There was no significant difference in the risk of cardiovascular system-related adverse events between the two groups (logRR = -0.12,95% CI -0.26 to 0.03, P = 0.12). Publication bias assessment showed significant bias only for PV (Egger's test Z = -2.89, P = 0.004) and PSA (Egger's test Z = -3.33, P = 0.001). Moderate to high heterogeneity was observed for some outcomes, with sub-group analysis suggesting that follow-up duration may be a major source of heterogeneity for PV. Sensitivity analysis confirmed the stability of the pooled effect estimates.

Conclusion: Combination therapy with α-ABs and 5α-RIs demonstrates superior efficacy compared with monotherapy in improving urinary symptoms, reducing prostate volume, increasing urinary flow rate, lowering PSA levels, and decreasing the risks of AUR and postoperative surgery, with a favorable safety profile. For BPH patients with severe symptoms and larger prostate volumes, combination therapy is recommended to achieve optimal therapeutic outcomes.