Introduction: Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a difficult disease to manage and creates critical limitations in patients' daily lives. Our objective was to determine the efficacy of hyperbaric oxygen (HBO) therapy in the maintenance of response after the administration of intravesical dimethyl sulfoxide (DMSO). Materials and Methods: We conducted an open, prospective, randomized, comparative pilot study with women diagnosed with IC/PBS according to the European Society for the Study of Interstitial Cystitis criteria. In the first phase, DMSO was given to all patients. In the second phase, we used 1:1 randomization and administered HBO to 10 women. The evaluated variables were pain (through a visual analog scale), frequency and urgency of voids, nocturia, and quality of life using the O'Leary-Sant Interstitial Cystitis Score/Problem Index and the King's Health Questionnaire. In the second phase, we measured the length of time that clinical improvement was maintained. Results: The mean age was 47.6 years (SD 18.4). Out of 20 patients, 14 experienced clinical improvement after DMSO in all of the evaluated symptoms (p < 0.05; 95% CI). After the second phase, all patients who received HBO had a more substantive and prolonged maintenance of the effects of DMSO. Conclusions: In this study, HBO improved the maintenance of the beneficial effects of DMSO among women with IC/PBS.

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