Botulinum toxin-A is ineffective in premature ejaculation treatment: insights from a meta-analysis of randomised controlled trials

The ejaculatory reflex consists of emission and expulsion, with the latter involving rhythmic muscular contractions that propel seminal fluid. Botulinum toxin, through its inhibitory effects, has been hypothesized to improve premature ejaculation (PE). This study evaluates high-quality evidence on botulinum toxin-A injections into the bulbospongiosal muscle as a treatment for PE. We conducted a systematic review and meta-analysis of randomised-controlled trials (RCTs) following PRISMA guidelines. Outcomes included intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) scores, and complications. Data were analysed using Microsoft Excel and R. ROB-2, Eggers test, and GRADE assessed risk of bias, publication bias, and certainty of evidence (CoE). Three RCTs were eligible, and covered data from 228 patients with (1:1) randomisation into intervention and control arms (100 units of botulinum toxin-A in 10 mLs versus 10 mLs of 0.9% NaCl). IELT increases were noted with averages of 39.6, 11.5, and 2.4 s at 1, 3, and 6 months of follow up, respectively. Likewise, PEP scores demonstrated improvements of 1.54, 1.08, and 0.36 units at the same follow up intervals. however, statistical significance was not achieved in both outcomes of interest. Post-procedural complications were recorded in 11 patients (9.6%) with 10 in the intervention group. The majority of patients had voiding difficulties (n = 5) & mild erectile dysfunction (n = 4), however, all adverse events (AEs) were self-resolving and did not require active treatment. Given our findings, current high-quality evidence does not support using Botulinum Toxin-A in the management of PE. Larger scale & standardised RCTs are recommended to conclusively outline its clinical benefits.