Abstract / Summary
Objectives To test whether adjunctive sildenafil improves the response to paroxetine in lifelong premature ejaculation (PE) and to explore whether SLC6A4 5-HTTLPR genotype modifies the effect.Methods In this randomized, double-blind trial, 80 men with lifelong PE were assigned 1:1 to paroxetine plus sildenafil or paroxetine plus matched placebo for 12 weeks. Twenty healthy men formed a non-interventional baseline genotype-reference cohort. The trial was prospectively registered at ClinicalTrials.gov (NCT07057011). The primary endpoint was Week-12 intravaginal ejaculatory latency time (IELT), analysed by ANCOVA on log-transformed values with log-baseline IELT as a covariate.Results Baseline geometric mean IELT was lower with combination therapy than monotherapy (41.77 vs 50.03 seconds; p = .004). After baseline adjustment, combination therapy had a higher Week-12 IELT (adjusted geometric-mean ratio 1.68, 95% CI 1.25–2.26; p = .001). Observed Week-12 geometric means were 214.65 and 137.28 seconds, respectively. Responder rates were 80.0% and 65.0% (p = .133), and any adverse-event rates were similar (65.0% and 60.0%; p = .818). A genotype-adjusted sensitivity analysis supported the treatment effect, but the treatment-by-genotype interaction was not significant.Conclusions Adjunctive sildenafil improved Week-12 IELT beyond paroxetine monotherapy after adjustment for baseline IELT. Genotype findings are exploratory because of small genotype strata, missing genotype calls, and the small healthy reference cohort.