Hyaluronic acid and chondroitin sulphate instillation in chronic bladder diseases: a meta-analysis

Objective: To systematically summarise and meta-analyse all uncontrolled and controlled studies evaluating the role of intravesical instillation of hyaluronic acid (HA), with or without chondroitin sulphate (ChS), in the treatment of bladder pain syndrome (BPS), recurrent urinary tract infection (rUTI) and post-radiation cystitis (pRC). Methods: A systematic review was conducted, and a protocol was registered with PROSPERO (CRD42025640480). Studies published between 1 January 1969 and 31 August 2024 were retrieved from multiple databases. Data were analysed using random-effects and common-effects models with subgroup and sensitivity analyses. Results: A total of 131 studies were retrieved, of which 30, 10 and three investigated the use of HA/ChS in patients with BPS and rUTI or pRC, respectively, and were included in the analyses. Conclusion: The use of HA/ChS resulted in a significant improvement in pain as well as voiding and irritative symptoms in all the investigated conditions. In addition, the treatment reduced the risk of rUTI when compared to standard care. Although limited data were available, when randomised controlled trials were investigated, the combined use of HA/ChS resulted in better outcomes and a lower infection rate compared to either placebo or standard of care (odds ratio 0.42 [95% CI 0.25; 0.49]; P < 0.0001). Finally, an improvement in sexual function and quality of life was also observed.