Published Dec 2, 2021

Xiang Xiao

Huan Deng

Mumba Mulutula Chilufya

Yizhen Lv

Yan Zhao

Jiaxin Liu

Ziwei Guo

Lichun Qiao

Jing Han  

Dong Wang

Chengjuan Qu


This paper has an erratum: https://bonoi.org/index.php/si/article/view/658

Currently, no suitable delivery methods are available for the drugs to interstitial cystitis/ bladder pain syndrome (IC/BPS). Herein we systematically evaluated the therapeutic effects of intravesical infusion of hyaluronic acid (HA) and chondroitin sulfate (CS) in patients with IC/BPS. This study includes randomized controlled trials (RCT) and self-controlled studies of IC/BPS patients treated with HA, CS, or both. English databases like PubMed, Cochrane Library, Embase, and Medline were searched until up to January 31, 2021. Information was extracted based on the inclusion and exclusion criteria, and then meta-analysis was performed. Sixteen studies including 491 patients were included and analyzed. The responsive rate of treatment was 91.24%. In 3 RCTs, the analogue scale (VAS) for pain on fix-effect model was [mean difference, MD -0.57 (95%CI, -1.55, -0.41)]. A significant improvement on random-effect model was [MD -2.78 (95%CI, -3.48, -2.07)] in 13 self-controlled studies. Outcomes on O’Leary-Sant Interstitial Cystitis Symptom Index, Problem Index, frequency, urgency, and bladder capacity were also significantly improved. Subgroup analysis showed significant difference between HA, CS, and the combination, and the perfusion of HA was more effective (Z = 29.97, P < 0.01). Also, different follow-up times after last treatment showed significant difference (Z = 7.69, P < 0.01). It can be beneficial for IC/BPS patients who have not responded to conventional treatments.



Interstitial cystitis, Bladder pain syndrome, Chondroitin sulfate, Hyaluronic acid, Meta-analysis

Supporting Agencies

This work was funded by the National Natural Science Foundation of China (81872567).

1. Lu P, Takai K, Weaver VM, Werb Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harbor Perspect Biol 2011; 3:a005058. DOI: https://doi.org/10.1101/cshperspect.a005058

2. Hynes RO. The extracellular matrix: Not just pretty fibrils. Science 2009; 326:1216-1219. DOI: https://doi.org/10.1126/science.1176009

3. Sasisekharan R, Shriver Z, Venkataraman G, Narayanasami U. Roles of heparan-sulphate glycosaminoglycans in cancer. Nat Rev Cancer 2002; 2:521-528. DOI: https://doi.org/10.1038/nrc842

4. Gorio A, Lesma E, Vergani L, Di Giulio AM. Glycosaminoglycan supplementation promotes nerve regeneration and muscle reinnervation. Eur J Neurosci 1997; 9:1748-1753. DOI: https://doi.org/10.1111/j.1460-9568.1997.tb01532.x

5. San Antonio JD, Winston BM, Tuan RS. Regulation of chondrogenesis by heparan sulfate and structurally related glycosaminoglycans. Develop Biol 1987; 123:17-24. DOI: https://doi.org/10.1016/0012-1606(87)90422-2

6. Hurst RE. Structure, function, and pathology of proteoglycans and glycosaminoglycans in the urinary tract. World J Urol 1994; 12:3-10. DOI: https://doi.org/10.1007/bf00182044

7. Parsons CL, Stauffer C, Schmidt JD. Bladder-surface glycosaminoglycans: An efficient mechanism of environmental adaptation. Science 1980, 208:605-607. DOI: https://doi.org/10.1126/science.6154316

8. Bedini E, Parrilli M. Synthetic and semi-synthetic chondroitin sulfate oligosaccharides, polysaccharides, and glycomimetics. Carbohydrate Research 2012; 356:75-85. DOI: https://doi.org/10.1016/j.carres.2012.02.010

9. French LM, Bhambore N. Interstitial cystitis/painful bladder syndrome. Am Fam Physician 2011; 83:1175-1181

10. Clemens JQ, Link CL, Eggers PW, Kusek JW, Nyberg LM, Jr., McKinlay JB. Prevalence of painful bladder symptoms and effect on quality of life in black, Hispanic and white men and women. J Urol 2007; 177:1390-1394. DOI: https://doi.org/10.1016/j.juro.2006. 11.084

11. Jensen H, Nielsen K, Frimodt-Møller C: Interstitial cystitis: review of the literature. Urol Int 1989; 44:189-193. DOI: https://doi.org/10.1159/000281502

12. Tirumuru S, Al-Kurdi D, Latthe P. Intravesical botulinum toxin A injections in the treatment of painful bladder syndrome/interstitial cystitis: A systematic review. Int Urogynecol J 2010; 21:1285-1300. DOI: https://doi.org/10.1007/s00192-010-1162-9

13. Birder L, Andersson KE. Urothelial signaling. Physiol Rev 2013; 93:653-680. DOI: https://doi.org/10.1152/physrev.00030.2012

14. Ha T, Xu JH. Interstitial cystitis intravesical therapy. Transl Androl Urol 2017; 6:S171-s179. DOI: https://doi.org/10.21037/tau.2017.06.18

15. Bschleipfer T, Doggweiler R, Schultz-Lampel D, de Jong J, Gonsior A, Hensen J, Heßdörfer E, Kaftan BT, Kuhn A, Kunzendorf U, Lampel A, Landmesser A, Loch A, Moormann O, Müller B, Neuhaus J, Reich A, Roth R, Schumacher S, Stratmeyer R, Vahlensieck W, Wördehoff A, Münder-Hensen B. Diagnostik und Therapie der interstitiellen Zystitis (IC/BPS): S2k-Leitlinie der Deutschen Gesellschaft für Urologie [Diagnosis and treatment of interstitial cystitis (IC/PBS) : S2k guideline of the German Society of Urology]. Urologe A 2019; 58(11):1313-1323. German. DOI: https://doi.org/10.1007/s00120-019-01054-2. Erratum in: Urologe A 2019; 58(12):1498.

16. Chintea CL, Belal M. Is there enough evidence for the use of intravesical instillations of glycosaminoglycan analogues in interstitial cystitis? BJU Int 2013; 111:192-193. DOI: https://doi.org/10.1111/j.1464-410X.2012.11635.x

17. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011; 343:d5928. DOI: https://doi.org/10.1136/bmj.d5928

18. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hróbjartsson A, Kirkham J, Jüni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schünemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355:i4919. DOI: https://doi.org/10.1136/bmj.i4919

19. Nickel JC, Hanno P, Kumar K, Thomas H. Second multicenter, randomized, double-blind, parallel-group evaluation of effectiveness and safety of intravesical sodium chondroitin sulfate compared with inactive vehicle control in subjects with interstitial cystitis/bladder pain syndrome. Urology 2012; 79:1220-1224. DOI: https://doi.org/10.1016/j.urology.2012.01.059

20. Lv YS, Zhou HL, Mao HP, Gao R, Wang YD, Xue XY. Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis. Int Urogynecol J 2012; 23:1715-1720. DOI: https://doi.org/10.1007/s00192-012-1802-3

21. Shao Y, Shen ZJ, Rui WB, Zhou WL. Intravesical instillation of hyaluronic acid prolonged the effect of bladder hydrodistention in patients with severe interstitial cystitis. Urology 2010; 75:547-550. DOI: https://doi.org/10.1016/j.urology.2009.09.078

22. Özkidik M. Assessment of long-term intravesical hyaluronic acid, chondroitin sulfate and combination therapy for patients with bladder pain syndrome. Cent Eur J Urol 2019; 72:270-275. DOI: https://doi.org/10.5173/ceju.2019.0007

23. Burak Arslan 1 SG, Ersin Gökmen 2, Oktay Özman 2, Mustafa Asım Avci 2, Enver Özdemir 2. Outcomes of intravesical chondroitin-sulfate and combined hyaluronic-acid/chondroitin-sulfate therapy on female sexual function in bladder pain syndrome. International urogynecology journal 2019. DOI: https://doi.org/10.1007/s00192-019-04036-2

24. Hung M-J, Tsai C-P, Lin Y-H, Huang W-C, Chen G-D, Shen P-S. Hyaluronic acid improves pain symptoms more than bladder storage symptoms in women with interstitial cystitis. Taiwan J Obstet Gynecol 2019; 58:417-422. DOI: https://doi.org/10.1016/j.tjog.2018.11.033

25. Akbay E, Çayan S, Kılınç C, Bozlu M, Tek M, Efesoy O. The short-term efficacy of intravesical instillation of hyaluronic acid treatment for bladder pain syndrome/interstitial cystitis. Turkish J Urol 2018; 45:129-134. DOI: https://doi.org/10.5152/tud.2018.35920

26. Porru D, Leva F, Parmigiani A, Barletta D, Choussos D, Gardella B, Daccò MD, Nappi RE, Allegri M, Tinelli C, Bianchi CM, Spinillo A, Rovereto B. Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis. Int Urogynecol J 2012; 23:1193-1199. DOI: https://doi.org/10.1007/s00192-011-1546-5

27. Nickel JC, Egerdie B, Downey J, Singh R, Skehan A, Carr L, Irvine-Bird K. A real-life multicentre clinical practice study to evaluate the efficacy and safety of intravesical chondroitin sulphate for the treatment of interstitial cystitis. BJU Int 2009; 103:56-60. DOI: https://doi.org/10.1111/j.1464-410X.2008.08028.x

28. Cervigni M, Natale F, Nasta L, Padoa A, Voi RL, Porru D. A combined intravesical therapy with hyaluronic acid and chondroitin for refractory painful bladder syndrome/interstitial cystitis. Int Urogynecol J 2008; 19:943-947. DOI: https://doi.org/10.1007/s00192-008-0572-4

29. Peng YC, Yueh-Hsia Chiu S, Feng M, Liang CC. The effect of intravesical hyaluronic acid therapy on urodynamic and clinical outcomes among women with interstitial cystitis/bladder pain syndrome. Taiwan J Obstet Gynecol 2020; 59:922-926. DOI: https://doi.org/10.1016/j.tjog.2020.09.021

30. Scarneciu I, Bungau S, Lupu AM, Scarneciu CC, Bratu OG, Martha O, Tit DM, Aleya L, Lupu S. Efficacy of instillation treatment with hyaluronic acid in relieving symptoms in patients with BPS/IC and uncomplicated recurrent urinary tract infections - Long-term results of a multicenter study. Eur J Pharm Sci 2019; 139:105067. DOI: https://doi.org/10.1016/j.ejps.2019.105067

31. Liang C-C, Lin Y-H, Hsieh W-C, Huang L. Urinary and psychological outcomes in women with interstitial cystitis/bladder pain syndrome following hyaluronic acid treatment. Taiwanese J Obstet Gynecol 2018; 57:360-363. DOI: https://doi.org/10.1016/j.tjog.2018.04.006

32. Butrick CW, Howard FM, Sand PK. Diagnosis and treatment of interstitial cystitis/painful bladder syndrome: A review. J Womens Health (Larchmt) 2010; 19:1185-1193. DOI: https://doi.org/10.1089/jwh.2009.1702

33. Tyagi P, Barclay D, Zamora R, Yoshimura N, Peters K, Vodovotz Y, Chancellor M. Urine cytokines suggest an inflammatory response in the overactive bladder: A pilot study. Int Urol Nephrol 2010; 42:629-635. DOI: https://doi.org/10.1007/s11255-009-9647-5

34. Liu HT, Shie JH, Chen SH, Wang YS, Kuo HC. Differences in mast cell infiltration, E-cadherin, and zonula occludens-1 expression between patients with overactive bladder and interstitial cystitis/bladder pain syndrome. Urology 2012; 80:225.e213-228. DOI: https://doi.org/10.1016/j.urology.2012.01.047

35. Zhang W, Deng X, Liu C, Wang X. Intravesical treatment for interstitial cystitis/painful bladder syndrome: A network meta-analysis. Int Urogynecol J 2017; 28:515-525. DOI: https://doi.org/10.1007/s00192-016-3079-4

36. Garzon S, Laganà AS, Casarin J, Raffaelli R, Cromi A, Sturla D, Franchi M, Ghezzi F. An update on treatment options for interstitial cystitis. Prz Menopauzalny 2020; 19:35-43. DOI: https://doi.org/10.5114/pm.2020.95334

37. Wyndaele JJJ, Riedl C, Taneja R, Lovász S, Ueda T, Cervigni M. GAG replenishment therapy for bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 2019; 38:535-544. DOI: https://doi.org/10.1002/nau.23900

38. Giusto LL, Zahner PM, Shoskes DA. An evaluation of the pharmacotherapy for interstitial cystitis. Expert Opin Pharmacother 2018; 19:1097-1108. DOI: https://doi.org/10.1080/14656 566.2018.1491968

39. Cervigni M, Natale F, Nasta L, Mako A. Intravesical hyaluronic acid and chondroitin sulphate for bladder pain syndrome/interstitial cystitis: long-term treatment results. Int Urogynecol J 2012; 23:1187-1192. DOI: https://doi.org/10.1007/s00192-012-1742-y

40. Pyo JS, Cho WJ. Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid/Chondroitin Sulfate Instillation for Interstitial Cystitis/Painful Bladder Syndrome. Cell Physiol Biochem 2016; 39:1618-1625. DOI: https://doi.org/10.1159/000447863

41. Kallestrup EB, Jorgensen SS, Nordling J, Hald T. Treatment of interstitial cystitis with Cystistat: A hyaluronic acid product. Scand J Urol Nephrol 2005; 39:143-147. DOI: https://doi.org/10.1080/00365590410015876-1

42. Parsons CL, Housley T, Schmidt JD, Lebow D. Treatment of interstitial cystitis with intravesical heparin. Br J Urol 1994; 73:504-507. DOI: https://doi.org/10.1111/j.1464-410x.1994.tb07634.x

43. Sant GR, Propert KJ, Hanno PM, Burks D, Culkin D, Diokno AC, Hardy C, Landis JR, Mayer R, Madigan R, Messing EM, Peters K, Theoharides TC, Warren J, Wein AJ, Steers W, Kusek JW, Nyberg LM; Interstitial Cystitis Clinical Trials Group. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol 2003; 170:810-815. DOI: https://doi.org/10.1097/01.ju.0000083020.06212.3d

44. Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB. Botulinum toxin A has antinociceptive effects in treating interstitial cystitis. Urology 2004; 64:871-875; discussion 875. DOI: https://doi.org/10.1016/j.urology.2004.06.073

45. Ham BK, Kim JH, Oh MM, Lee JG, Bae JH. Effects of combination treatment of intravesical resiniferatoxin instillation and hydrodistention in patients with refractory painful bladder syndrome/interstitial cystitis: A pilot study. Int Neurourol J 2012; 16:41-46. DOI: https://doi.org/10.5213/inj.2012.16.1.41
How to Cite
Xiao, X., Deng, H., Chilufya, M. M., Lv, Y., Zhao, Y., Liu, J., Guo, Z., Qiao, L., Han, J., Wang, D., & Qu, C. (2021). Chondroitin Sulfate and Hyaluronic Acid Perfusion for Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis. Science Insights, 39(4), 361–373. https://doi.org/10.15354/si.21.re266

Similar Articles

You may also start an advanced similarity search for this article.