Effect of nebivolol on erectile function: a systematic review and meta-analysis of randomized controlled trials

Background: Historically, β-blockers have been associated with erectile dysfunction (ED). Nebivolol, a third-generation β-blocker, may have had no negative effect on erectile function because of its vasodilating properties. However, the evidence level was considered either as low or very low.

Aim: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of nebivolol on erectile function.

Methods: All published RCTs were searched through PubMed, Cochrane Library, Web of Science, and Embase until October 2023. Review Manager version 5.3.0 was used for statistical analysis. Sensitivity analyses were performed by excluding each study using Stata 17 software.

Outcomes: The primary outcome was the International Index of Erectile Function (IIEF)-5 score. We excluded publication types, including letters, reviews, and meta-analyses.

Results: We identified four RCTs in this meta-analysis. All included studies compared the effects of nebivolol vs metoprolol on erectile function. Eight parallel groups with 397 individuals reported IIEF-5 scores. A random-effect model revealed that the IIEF-5 score was significantly higher in the nebivolol group (MD 1.81, 95%CI 0.95-2.68, P < .0001, I2 = 99%). We conducted a sensitivity analysis by removing each individual study and observed that there was no significantly different result. Furthermore, we conducted a prespecified subgroup analysis based on the dosage of metoprolol, patients with ED at the time of enrollment, and disease type. Subgroup analysis revealed that heterogeneity significantly decreased, and the result of the IIEF-5 score was stable and consistent.

Clinical implications: Our results provides stronger evidence that nebivolol significantly reduced the risk of ED occurrence or progression.

Strengths and limitations: Our meta-analysis included high-quality RCTs and conducted a predetermined subgroup analysis. However, the main limitations are the limited number of included studies and their heterogeneity.

Conclusion: Our meta-analysis provided stronger evidence that nebivolol significantly reduced the risk of ED occurrence or progression compared with metoprolol, irrespective of whether the patient had ED or not. This meta-analysis could serve as an important reference for future studies in this field.