(253) Usage of Hyaluronic Acid in Urology: Systematic Review and Meta-Analysis
Authors: Moukhtar Hammad MA , Roth B , Sultan M , Banton J , Park SH , Perito P , Yafi FA , Raheem OA 
Published: February 2024

Abstract

Introduction
The use of hyaluronic acid (HA) as a non-surgical treatment for various pathological and cosmetic conditions within urology has been of great interest in recent literature. HA has been studied for use in several conditions including Peyronie’s disease, penile size augmentation, and premature ejaculation. Currently, HA is not first-line or standard therapy for any of these conditions; however, it has been increasingly utilized in clinical practice.

Objective
To provide an updated review and meta-analysis of the current state of hyaluronic acid use in urology, characterize its adverse effects, as well as briefly discuss future directions of research for HA in urology.

Methods
Multiple PubMed search strategies were run utilizing search terms, including: “hyaluronic acid”, “penile OR penis”, “augmentation”, “injection”, “enhancement”, “Peyronie disease”, “penile fibromatosis”, “premature ejaculation”, “cosmetic urology OR genital cosmetic”, “men’s health”, and “penile diseases” among other related iterations. Relevant data extracted included mean and standard deviation (for both pre- and post-HA injection or control treatment): International Index of Erectile Function (IIEF-5) score, intravaginal ejaculatory latency (IELT), glandular circumference/girth, erect penile girth, and plaque size.

Results
Our search strategies yielded 136 studies of which 33 studies were included for systematic review (Figure 1). Among all studies, complications were generally rare with the procedure. 4 studies reported penile ecchymosis and a study reported paresthesia and numbness. There was 1 case report of glans penis necrosis, two of abscess formation, one of acute hypersensitivity reaction, and one of sepsis secondary to HA injection, which represented the most serious complications reported. Several studies also reported irregular nodule formation, which resolved with time or mild pressure application. In the metanalysis, 16 studies were included. IELT, penile girth, glans circumference, and IIEF-5 were all significantly increased on a fixed-effects model. 9 studies examined the change in IELT after HA injection, with an effect size of 2.335 [2.147,2.522], p-value= &lt;0.001 (figure 2). Regardless of intent of study, 4 studies reported increase in glans circumference (figure 3) with effect size: 2.3 [2.066, 2.534], p-value= &lt;0.001. Similarly, 4 studies showed increase in penile girth (figure 4) with effect size: 1.729 [1.504, 1.954], p-value = &lt;0.001. 3 studies demonstrated IIEF-5 improvement with effect size: 0.996 [0.739-1.252], p-value= &lt;0.001. With only 2 studies reporting pre- and post-op plaque length while others reporting the mean reduction in plaque amount, the plaque size was generally reduced after HA treatment, but this was not statistically significant, p-value= 0.069 with effect size: -0.252 [-0.524, 0.019]. It should be noted that of the 26 primary studies (excluding the 7 case reports), only 7 studies were randomized, controlled studies while others were either retrospective or single arm in nature.

Conclusions
While the use of HA in urology shows promising results in terms of efficacy and minimal side effects, there is a need for more randomized controlled trials to validate its potential advantages. Future research should focus on optimizing treatment protocols and exploring the expertise of sexual medicine specialists in administering HA therapy.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.