Clinical efficacy and safety of hyaluronic acid gel injection in the glans penis for treatment of premature ejaculation: systematic review and meta-analysis

Abstract Background In recent years, there has been growing interest in the use of hyaluronic acid (HA) for the treatment of premature ejaculation (PE). The efficacy of this treatment is quite controversial. Aim This study intended to evaluate the efficacy and safety of glans penis augmentation with HA gel for PE. Methods This systematic review includes randomized controlled trials (RCTs), primary clinical trials, prospective and retrospective studies, case series, and case reports. Searches in Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov were performed blindly by 2 reviewers. Outcomes Intravaginal ejaculation latency time (IELT), questionnaires about PE, glans circumference (millimeters), and adverse events. Results Thirteen studies were included in the evaluation: 4 RCTs, 8 prospective observational studies, and 1 restrospective study. The number of patients who received HA gel on the glans penis was 706. According to the results of 2 placebo-controlled RCTs, HA gel treatment significantly improved IELT at the end of the first month (mean difference [MD], 65.44 seconds). In the first month after the HA gel injection procedure, IELT increased vs before the procedure (MD, 176.18 [95% CI, 146.89-205.48]; P < .001, I2 = 83%). When the IELT values ​​were compared at 6 months after HA gel application, IELT improved vs before the procedure (MD, 143.93 [95% CI, 124.78-163.09]; P < .001, I2 = 82). The glans circumference expanded by approximately 1.5 cm after the procedure (MD, 14.82 mm [95% CI, 12.75-16.90]; P < .001, I2 = 65%). When the side effect profile of other studies was examined, side effects were observed in 91 patients after HA gel injection applied to 598 patients (15.22%). Among these side effects, the most common were pain (n = 46, 7.69%), bulla/nodule formation (n = 25, 4.18%), and ecchymosis (n = 20, 3.34%). Conclusion While HA shows promise as a therapeutic option for PE, ongoing research is essential to elucidate its clinical utility, mechanisms of action, and comparative efficacy.