Bladder Pain Syndrome (BPS), often referred to as Interstitial Cystitis (IC), is a chronic urological condition that affects millions of individuals worldwide. Described by recurrent pain, pressure, or discomfort in the bladder and the pelvic region, BPS/IC is a syndrome that not only poses diagnostic and therapeutic problems for clinicians and researchers due to its elusive and poorly understood nature but also dramatically alters the lives of those who are diagnosed with this disorder [1]. Urinary urgency and frequency are common complications of BPS/IC and these complications can become physically as well as emotionally tiring which consequently causes a lower quality of life. A major difficulty affecting the management of BPS/IC is their defining as the prevalence of the diseases significantly differs depending on the selected population samples, the criteria of diagnosis used in the study, as well as the research methods applied [2]. The prevalence ranges from as low as 6% to as high as 12% which points to the fact that this condition is hard to diagnose. One of the factors that have contributed to these disparities is the absence of a codified definition of BPS/IC, which has resulted in disparate diagnostic approaches [3,4]. Nevertheless, studies have identified that BPS/IC also exists in men but it is less diagnosed cause of male patients are generally diagnosed with chronic prostatitis. Thus, the fact of gender differences in this respect demonstrates that further studies of the causes of this disease and its manifestations depending on demographic factors are necessary [5,6].   The epidemiology of BPS/IC has been established to show considerable geographical differences. BPS/IC has been reported more frequently in the Western countries and the epidemiology of this condition has also been investigated in detail in these regions. For instance, experts approximate that in USA only 3 to 8 million women and 1 to 4 million men might be suffering from BPS/IC [7]. Another similar trend is seen in European countries; as with a Finnish study that showed prevalence ranging one percent. 2% for women of the age 18 to 79 years. These statistics show that BPS/IC can be a significant cost concern and given that many people are still not diagnosed correctly or diagnosed with similar urological and/or gynecological conditions [8]. There is not enough information about BPS/IC from Asian countries, but the available data indicate that the prevalence of BPS/IC might be lower in Asians. For instance, the research carried out in Japan and Korea shows lower rates as compared to those of the western world [9]. However, these are not necessarily due to the real differences in prevalence of such diseases but could be due to differences in awareness, in diagnosing the diseases and culture in general acceptance of chronic pain. The reasons for the differences in BPS/IC incidence include the differences in diagnostic criteria, the level of patients’ awareness, and the availability of medical care [10]. Diagnostic criteria of BPS/IC have been changing throughout the years with initial emphasis given to strictly defined cases with characteristic cystoscopic appearance, namely Hunner’s lesion. However, current definitions included a wider range of symptoms and included non-ulcerative forms of BPS/IC making prevalence rate in recent studies to be higher. Self-reporting and patient awareness is also widely used in prevalence studies as well [11]. Described at times as a ‘masquerader’ – BPS/IC is frequently under-diagnosed specifically because of the symptoms related to chronic pelvic pain [12]. This underreporting distorted the prevalence of skewed data especially among the developing countries where the patients with these diseases do not get easy access to health facilities and in general BPS/IC where little or no awareness exists. As to the etiology of the condition, there are many theories, but the experimental research has not produced consistent results and medication is often not helpful [13]. Hence, BPS/IC is a clinicopathological diagnosis that entails consideration of patients’ symptoms. Prior efforts to estimate BPS/IC prevalence have employed method such as, chart review of convenience samples, self-administered newsletters mailed to convenience samples of patients, medical records review, area probability sampling in a restricted geographic area and mail survey on a small probability sample of the population [14]. This study was carried out with the objective to determine the of bladder pain syndrome / interstitial cystitis symptoms among women attending tertiary care hospital in central region of Saudi Arabia.

Study design and setting This cross-sectional study was conducted at King Khalid Hospital, Majmaah, Saudi Arabia from May 2021 to April 2024. The study included 800 patients, comprising females aged 18 years and above.   Inclusion and exclusion criteria Female participants who have experienced chronic pelvic pain, urinary urgency, and frequency for at least six months without any identifiable infection or other clear cause were included in the study. Patients with active urinary tract infections, bladder cancer, or any other diagnosed condition that could account for their symptoms were excluded.   Sample size calculation The sample size was calculated using the following formula for cross-sectional studies, facilitated by Raosoft software used for calculating sample size formulas in population-based studies (http://www.raosoft.com/samplesize.html): n = (Z² * σ²) / E²   where:n = sample sizeZ = Z-score corresponding to the desired confidence level (95% confidence level, Z = 1.96)σ = standard deviation of the population (unknown, assumed to be 0.5)E = margin of error (5%)   Using a prevalence of BPS/IC of 10% (based on previous studies), the estimated sample size was: n = (1.96² * 0.5²) / 0.05²n ≈ 785.44 Rounding up to the nearest whole number, the sample size was set at 800 participants.   Data collection instrument Data were collected through a combination of patient questionnaires and clinical evaluations. The Interstitial Cystitis Symptom Index (ICSI) questionnaire, a validated and widely used tool, was used to assess symptoms associated with Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC). The ICSI questionnaire, created by the Interstitial Cystitis Association, is a proven tool in assessing the severity and burden of BPS/IC in patients (https://www.baus.org.uk/_userfiles/pages/files/Patients/Leaflets/IC%20symptom%20score.pdf).     Questionnaire design The ICSI survey has eight questions, broken down into two parts. The initial portion has 4 questions, they all deal with how often, how bad, and how long urinary and pelvic pain symptoms have been present. How often have you felt the strong need to urinate with little or no warning? Or have you ever gone to urinate less than 2 hours after you just finished peeing? How often did you, most typically, get up at night to urinate? Have you experienced pain or burning in your bladder? 0-5 scale for each question, the higher the score the worse the symptoms. The second part is about how much the symptoms affect everyday life, and there are 4 questions. Frequent urination during the day? Getting up at night to urinate? Need to urinate with little warning? Burning pain, discomfort, or pressure in your bladder? Each question is rated on a scale of 0-4, with higher scores indicating more severe symptoms.   Data collection procedure Participants completed the ICSI questionnaire during their hospital visit, with trained healthcare professionals available to assist with any questions or clarifications, ensuring accurate data collection and minimizing the risk of misinterpretation. Reliability was checked using Cronbach's alpha of 0.87 and is an indicator of high internal consistency, along with establishing validity for the variables being targeted properly.   Statistical analysis Data were analyzed using SPSS v27.0. Mean and standard deviation were estimated for quantitative variables. Frequencies and percentages were calculated for qualitative variables the statistical significance was set at p < 0.05. Descriptive statistics summarized demographic data, and a multivariate regression analysis examined the associations between age (dependent variable) and urinary symptoms that included urgency to urinate and nocturnal episodes and IBS status (independent variables). To corroborate these findings and test the robustness of our results, sensitivity analyses were conducted in which subgroups with potentially significant comorbid conditions, such as anxiety and depression or other psychiatric conditions, were excluded from the analysis.

Data were collected from 800 participants. A significant majority, 57.6%, reported never experiencing a sudden urge to urinate, while 14.1% felt this urge almost always. When it came to frequent urination, 27.6% of respondents never had to urinate within two hours of their last visit, but 13.9% experienced this almost always. Night-time urination was common, with 39.6% waking up once per night and 27.6% not waking at all. Regarding pain or burning in the bladder, 55.8% of participants never experienced these symptoms, while 20.9% reported it sometimes, and 16.4% experienced it several times as presented in Table 1. Table 1: Interstitial Cystitis (IC) Symptoms Index  Questions Response Frequency Percent Over the past month, how many times have you felt the urge to urinate suddenly? Never at all 461 57.6 Less than once in five times 133 16.6 Less than half the time 55 6.9 About half the time 19 2.4 More than half the time 19 2.4 Almost always 113 14.1 Over the past month, have you had to urinate less than two hours after you finished urinating? Never at all 221 27.6 Less than once in five times 222 27.8 Less than half the time 115 14.4 About half the time 38 4.8 More than half the time 93 11.6 Almost always 111 13.9 Over the past month, how many times have you woken up at night to urinate? Never 221 27.6 One time 317 39.6 Twice 150 18.8 Three times 56 7.0 Four times 38 4.8 Five times or more 18 2.3 Over the past month, have you had pain or burning in your bladder? Never at all 446 55.8 Sometimes 167 20.9 Several times 131 16.4 Usually 38 4.8 Almost always 18 2.3 Frequent urination during the day was not a problem for 46.6% of participants, but 25.9% reported it as a small problem, and 9.3% as a moderate issue. Nighttime urination posed no problem for 56.0% of respondents, yet 11.6% found it moderately troublesome. Sudden urges to urinate were generally not problematic, with 58.0% reporting no issues, though 21.1% experienced it as a very small problem. Bladder pain or pressure caused no issues for 62.6% of participants, but 11.9% reported moderate problems, and 7.0% considered it a significant issue as it shown in table 2.   Table 2: Interstitial Cystitis (IC) Problem Index  Questions Response Frequency Percent Over the past month, how much frequent urination during the day has caused you a problem? Never 373 46.6 Very small problem 109 13.6 Small problem 207 25.9 Moderate problem 74 9.3 Big problem 37 4.6 Over the past month, how much waking up at night to urinate has caused you a problem? Never 448 56.0 Very small problem 147 18.4 Small problem 75 9.4 Moderate problem 93 11.6 Big problem 37 4.6 Over the past month, how much did you need to urinate suddenly and cause you a problem? Never 464 58.0 Very small problem 169 21.1 Small problem 73 9.1 Moderate problem 57 7.1 Big problem 37 4.6 Over the past month, how much burning, pain or pressure in your bladder has caused you a problem? Never 501 62.6 Very small problem 148 18.5 Small problem 0 0.0 Moderate problem 95 11.9 Big problem 56 7.0   Anxiety and depression were the most common comorbidities, affecting 23.4% of participants, highlighting a significant overlap between psychological distress and BPS/IC. Thyroid diseases were present in 9.5% of the population, followed closely by hypertension at 9.3% and diabetes at 9.0%. Heart disease was less prevalent, affecting only 2.4% of participants (Table 3).   Table 3: Comorbidities  Comorbidities Frequency Percent Diabetes 72 9.0 Hypertension 74 9.3 Thyroid diseases 76 9.5 Heart disease 19 2.4 Anxiety and depression 187 23.4 About 30.1% of participants reported not suffering from IBS, 39.8% struggled with it on some days, and 18.5% experienced symptoms more than half the days. Notably, 11.6% of participants reported always dealing with IBS symptoms. These results indicate a strong comorbidity between BPS/IC and IBS, suggesting that a substantial number of patients with bladder pain syndrome also face gastrointestinal challenges, which may further complicate their overall health and quality of life (Table 4).   Table 4: Do you suffer from irritable bowel syndrome (abdominal pain and gas, diarrhea and constipation, fatigue and body fatigue?   Irritable bowel syndrome Frequency Percent I don't suffer 241 30.1 I struggle some days 318 39.8 More than half the days 148 18.5 Always 93 11.6 Total 800 100.0 The Interstitial Cystitis Symptom Index (ICSI) had a mean score of 5.10, with a standard deviation of 4.44, indicating a wide variation in symptom severity across the population. The median ICSI score was 3.00, with an interquartile range (IQR) of 2.0 to 7.0, and scores ranged from 0 to 19. The Interstitial Cystitis Problem Index (ICSPI) had a lower mean score of 3.64 and a standard deviation of 4.35, with a median score of 2.00 and an IQR of 0.0 to 6.0, suggesting variability in the perceived impact of symptoms on daily life. The participants' ages showed a mean of 38.30 years, with a standard deviation of 10.53, a median of 36.00 years, and an IQR of 31.0 to 45.0 years, with ages ranging from 20 to 70 years (table 5).   Table 5: Interstitial Cystitis (IC) Symptoms Index Score and Interstitial Cystitis (IC) Problem Index Score Statistics  PARAMETER Mean Std. Deviation Median IQR Minimum Maximum ICSI_SCORE 5.10 4.44 3.00 (2.0-7.0) 0 19 ICSPI_SCORE 3.64 4.35 2.00 (0.0-6.0) 0 16 Lifetime 38.30 10.53 36.00 (31.0-45.0) 20 70   The regression analysis indicated that the further along a participant reported being towards having a rising urge to urinate, the more the predicted age decreased (Table 6). On the contrary, the strength of waking up at night to urinate and increased severity of IBS symptoms was positively correlated with the increase in a predicted age. These correlations were statistically significant, indicating a strong association between these urinary symptoms, IBS severity, and age in the population studied.   Table 6: Multivariate Regression Results Variable Coefficient p-value Intercept 27.11 0.001 Urge to urinate -4.41 0 Waking up at night to urinate 6.18 0 In the sensitivity analysis (Table 7), after excluding participants with comorbidities, the results showed that the associations between urinary symptoms, IBS severity, and age remained statistically significant. As the urge to urinate increased, the predicted age decreased. Conversely, more frequent nighttime urination and higher IBS severity were still associated with an increase in age. The overall effect sizes were slightly reduced compared to the original analysis, but the relationships remained consistent.   Table 7: Sensitivity Analysis Results Variable Coefficient p-value Intercept 25.85 0 Urge to urinate -2.65 0 Waking up at night to urinate 5.17 0      

The results of the survey showed that the respondents had mild to severe symptoms and the level of urinary symptoms and bladder discomfort varied sharply. The Intercultural Cystitis Symptom Index (ICSI) and Intermittent Cystitis Problem Index (ICSPI) show variation in the BPS/IC sufferers. The mean ICSI score, of 10 respectively and ICSPI score of 3. 64 show that, although some cases reveal a low level of manifested pathology, others include more serious difficulties [15]. This range of results witnessed by standard deviation and interquartile range is further emphasized by the symptoms’ variability and the extent of the patient’s daily life impairment [16]. The relatively low median indicates that quite a significant part of individuals might get signs that are hardly severe from the perspective of a high index. Nevertheless, the detection of some outliers suggests that BPS/IC can be extremely incapacitating for some people [17]. The results of the study on urinary symptoms are consistent with the previous research on BPS/IC; this study also demonstrated that, in patients with BPS/IC, present symptoms include urinary urgency, frequency, and nighttime urination. Despite 46.2% of participants indicating that they hardly ever experienced a decreased amount of urine passed at night, 6% said it was never an issue in their lives. 9% described it as a very small issue 5%, a moderate problem 22%, and a large issue 9%. Six percent of respondents said that they had a moderate issue with it while 3% labeled it as a minor one [18]. The mean ICSI score of 5.10 and ICSPI score of 3.64 indicate that while some participants experienced mild symptoms, others faced more severe challenges. The broad range of scores, as indicated by the standard deviations and interquartile ranges, reflects the heterogeneity in symptom presentation and the degree to which these symptoms interfere with daily life. The lower median scores suggest that a substantial portion of the population might experience symptoms that, although present, are not overwhelmingly severe [19]. However, the presence of extreme scores underscores the debilitating nature of BPS/IC for a subset of patients. The study's findings on urinary symptoms align with existing literature on BPS/IC, where symptoms such as urinary urgency, frequency, and nighttime urination are prevalent. Despite 46.6% of participants reporting that frequent daytime urination was never a problem, a significant proportion, 25.9%, found it to be a small problem, and 9.3% rated it as a moderate problem. Similarly, nighttime urination did not pose a problem for 56.0% of respondents, but 11.6% found it moderately troublesome [20]. This suggests that all these conditions are mutually reinforcing and they result in increased symptom burden which hampers the treatment process and minimizes the quality of life of such patients. The fact that the age ranged from 20 to 70 years of age also depicts that even young people are at risk of BPS/IC, therefore requiring age-sensitive management [21]. This study has some limitations also. First, its cross-sectional design restricts the ability to infer causality between BPS/IC and comorbid conditions like anxiety or IBS. Second, potential selection bias may exist, as participants were drawn from a specific population, which could limit the generalizability of the findings. Third, reliance on self-reported data introduces the risk of recall bias, potentially affecting the accuracy of the responses.

It is concluded that bladder pain syndrome/interstitial cystitis (BPS/IC) significantly impacts a subset of women attending tertiary care, with varying degrees of symptom severity and associated comorbidities such as anxiety, depression, and IBS. The study highlights the significant variability in BPS/IC symptoms and their impact on daily life. The high prevalence of comorbid conditions, particularly anxiety, depression, and IBS, suggests that BPS/IC is part of a broader syndrome that requires comprehensive management.   Data availability The data supporting this study's findings are available from the corresponding author upon reasonable request.   Conflicts of Interest The authors declare that there is no conflict of interest regarding the publication of this article.   Institutional Review Board statement This study was approved by the institutional review board of the Deanship of Scientific Research at Majmaah University with IRB No. 20-270E dated May 2020.   Informed consent statement Consent was obtained rom the participants before they were enrolled in thew study. Authors' contributions Conceptualization, Methods, Data collection, Data analysis, Manuscript write up and review was done by Suleman Almutairi   Funding Not funded   Acknowledgments I would like to thank the Director of King Khalid Hospital for helping us to conduct this study.