Are We Missing the Bladder? Reflections on Endometriosis and IC/BPS

Endometriosis and interstitial cystitis/bladder pain syndrome (IC/BPS) frequently coexist in women with chronic pelvic pain, yet overlapping symptoms and non-standardized diagnostic pathways often delay recognition of dual pathology. We propose that a structured surgical approach combining laparoscopy and diagnostic cystoscopy may improve identification and clinical characterization of this overlap. On the basis of prospective surgical experience in women with suspected endometriosis and concomitant bladder symptoms, optical assessment enables phenotypic differentiation of bladder-centric and non–bladder- centric IC/BPS. When cystoscopic features are present, initiation of a standardized bladder-directed therapeutic strategy alongside endometriosis treatment may enhance symptom control and reduce persistent pain. Systematic evaluation during a single surgical setting has the potential to increase diagnostic precision, minimize incomplete interventions, and support individualized, mechanism-based management. This opinion highlights the importance of integrated diagnostic algorithms and multidisciplinary care models to address the complex interplay between endometriosis and IC/BPS.

Endometriosis · Interstitial cystitis · Chronic pelvic pain Endometriosis is a benign, estrogen-dependent, and het- erogeneous gynecological disorder characterized by the presence of endometrial-like tissue outside the uterine cavity, resulting in a persistent inflammatory response [1 ]. This condition affects approximately 10–15% of women of reproductive age and is associated with a wide spectrum of clinical manifestations [2]. Common symptoms include dys- menorrhea, dyspareunia, and abdominal pain, while some patients may also experience dyschezia, dysuria, and urinary frequency [3, 4]. These symptoms often result in a signifi- cant reduction in quality of life. Disease extent and sever - ity are described using several classification systems, most commonly the Revised American Society for Reproductive Medicine (rASRM) score and the #Enzian classification [5, 6]. While the rASRM system provides a general assessment of superficial endometriosis, the #Enzian classification is better suited for staging deep infiltrating and more severe forms of the disease [7]. Recently, phenotype-based classification systems have been proposed, offering a more comprehensive framework by integrating lesion morphology and anatomical involve- ment [8]. Four principal phenotypes of endometriosis may occur independently or concurrently: superficial peritoneal endometriosis, ovarian endometriosis, uterine endometrio- sis (adenomyosis), and deep endometriosis (DE) [9 ]. Deep endometriosis is characterized by nodular lesions infiltrat- ing beneath the peritoneal surface (> 3 mm) or penetrating the muscular layer of pelvic or visceral organs, frequently inducing fibrotic reactions and distortion of normal anatomy [10]. This subtype is considered a severe form of the disease, affecting approximately 20% of women with pelvic endome- triosis and often involving pelvic organs extensively, leading to significant morbidity [10]. To address the critical 8-to-10-year diagnostic latency, the current European Society of Human Reproduction and Embriology (ESHRE – 2022) and American Society Repro- ductive Medicine (ASRM—2024) guidelines has moved Handling Editor: Rok Šumak Editor in Chief: Kaven Baessler * Giovanni Di Favero [email protected] 1 Department Gynecology and Obstetrics, Justus-Liebig University, University Hospital Giessen-Marburg (UKGM), Campus Giessen, Giessen, Germany 2 Department Gynecology and Obstetrics, Asklepios Hospital Lich, Justus-Liebig University, Baumgarten 32, 35394 Lich, Germany International Urogynecology Journal from a surgery-dependent model to a multimodal clinical framework that integrates structured screening question- naires, physical exam, and high-resolution imaging (ultra- sonography/magnet ressonance imaging) for noninvasive prediction of the disease [11, 12]. This concept intends to facilitate initiation of empirical treatment, while reserving laparoscopy with histological verification (traditionally the definitive gold standard) for complex or imaging-negative cases. More recently, the development and progressive implementation of microRNA signatures, together with the use of targeted questionnaires, have shown promise in expediting diagnosis [13, 14]. Earlier identification enables timely therapeutic intervention, which may not only slow lesion progression but also help prevent pain centralization and chronification. First-line management of endometriosis consists of medical therapy with combined oral contracep- tives or progestin-based treatments [12]. In cases of treat- ment failure, surgical intervention is considered as second- line therapy, with the extent of surgical radicality tailored to the patient’s symptoms and reproductive desires. Despite extensive research, the exact pathophysiology of endometriosis remains incompletely understood and is considered multifactorial, involving genetic, immunologi- cal, hormonal, and environmental influences [ 15]. Several theories have been proposed to explain the development of endometriosis. Retrograde menstruation remains the most widely accepted hypothesis, although it fails to account for cases in non-menstruating individuals. Alternative mecha- nisms include vascular and lymphatic dissemination, which suggest systemic spread of endometrial cells, and coelomic metaplasia, whereby peritoneal cells transform into endome- trial-like tissue [16]. Genetic and epigenetic factors further modulate disease susceptibility and progression. At the molecular level, endometriosis progression is driven by dysregulated pathways involved in cellular adhe- sion, invasion, and resistance to apoptosis [17]. Elevated local estradiol production and progesterone resistance, often mediated by epigenetic modifications, promote lesion sur - vival and proliferation [18, 19]. Inflammation and immune dysfunction are central to endometriosis pathogenesis. Acti- vated peritoneal macrophages secrete excessive proinflam- matory cytokines, while reduced natural killer cell activity impairs immune-mediated clearance of ectopic endometrial cells [20, 21]. Moreover, recurrent microbleeding from the lesions contribute to tissue damage, perpetuating chronic inflammation, fibrosis, and pain [22]. Consequently, endo- metriosis is associated with chronic pelvic pain (CPP) in up to 80% of affected women [23]. Chronic pelvic pain (CPP) is a common and debilitating condition affecting approximately 6–25% of women of all ages worldwide, with reported prevalence varying depend- ing on the definition applied [24, 25]. To date, no univer - sally accepted definition or diagnostic criterion for CPP has been established. The American College of Obstetricians and Gynecologists (ACOG), in collaboration with the ReVI- TAlize initiative, describes as non-cyclic lower abdominal pain persisting for at least 6 months, which may be constant or intermittent and can be exacerbated by menstruation or sexual intercourse [ 26]. CPP is associated with significant impairments in quality of life, reduced work productivity, and increased healthcare utilization [25]. A recent system- atic review estimated the annual economic costs of CPP to be approximately USD 2.8 billion [27]. From a clinical per- spective, CPP accounts for nearly 10% of gynecological con- sultations, approximately 12% of hysterectomies, and more than 40% of diagnostic laparoscopies [26, 28]. Although the pain is localized to the pelvic region, its perception is ultimately mediated by central nervous sys- tem (CNS) processing [29]. Endometriosis shares multiple clinical and pathophysiological features with chronic pelvic pain. Women with these conditions often exhibit alterations in brain structure and function, consistent with central sen- sitization and dysfunctional pain processing mechanisms. In endometriosis-associated pain, persistent peripheral inflam- mation and nociceptive input can further drive central sen- sitization, contributing to pain persistence even after lesion resection or hormonal suppression. Therefore, early and accurate diagnosis, followed by timely initiation of therapy, is critical to interrupt these processes and potentially pre - vent pain chronification and long-term CNS alterations [30]. Nevertheless, delayed diagnosis remains a major challenge in the management of both CPP and endometriosis, with up to 50% of affected women remaining without a defini- tive diagnosis even after years of symptoms [31]. Despite its high prevalence and substantial socioeconomic impact, CPP has been described by the World Health Organization (WHO) as a “neglected reproductive health morbidity” [25]. This designation reflects persistent deficiencies in healthcare systems, prioritization, and resource allocation across differ- ent regions of the world [31]. In the context of chronic pelvic pain (CPP), the presence of a prior diagnosis of endometriosis should not preclude comprehensive evaluation for additional or overlapping eti- ologies. The differential diagnosis spans multiple medical specialties, including gastrointestinal, gynecologic, urologic, musculoskeletal, and psychiatric or psychosomatic disorders [32]. Management of CPP is extremely challenging due to the wide range of nonspecific symptoms and numerous pos- sible underlying conditions, including depression—affect- ing up to 50% of patients—and anxiety [25]. Despite the frequent use of invasive diagnostic procedures, patients with CPP are often treated empirically for presumed diagnoses, which frequently results in poor response [31]. As a result of their frustration with these suboptimal outcomes, many patients consult multiple healthcare providers and undergo repeated medical and surgical interventions [32]. International Urogynecology Journal Pelvic pain of bladder origin has received increasing recognition since the initial descriptions of interstitial cys- titis (IC) in 1887 and painful bladder syndrome (PBS) in 1957 [33]. These conditions are defined by the American Urological Association (AUA) and the International Con- tinence Society (ICS) as chronic disorders characterized by pain, pressure, or discomfort perceived to originate from the urinary bladder, accompanied by lower urinary tract symptoms, such as dysuria, nocturia, frequency, and urgency, persisting for more than 6 weeks in the absence of infection or another identifiable cause [34, 35]. In contrast, the European Society for the Study of Interstitial Cystitis defines the condition based on the presence of at least one urinary symptom in combination with characteristic cys- toscopic findings [36]. Although it was once considered a rare condition, more recent studies indicate a prevalence of 2.7% to 6.5% among women, with peak incidence occurring between 40 and 60 years of age [33, 34]. While interstitial cystitis (IC) traditionally refers to cases with characteristic bladder findings, such as Hunner’s lesions identified on cys- toscopy, bladder pain syndrome (BPS) represents a broader, symptom-based diagnosis that includes patients experienc- ing bladder-associated pain in the absence of these specific cystoscopic features [37]. Cystoscopy may contribute to the diagnostic evaluation of selected patients with suspected IC/BPS by enabling direct visualization of characteristic bladder findings. However, cystoscopic abnormalities should be interpreted cautiously, particularly glomerulations, which are increasingly recog- nized as nonspecific findings that may also occur in other pelvic pain conditions or even after instrumentation itself. The most clinically relevant cystoscopic features include Hunner’s lesions, areas of mucosal erythema, edema, and, less specifically, glomerulations. Increasing evidence indi- cates that IC/BPS is a heterogeneous condition, encompass- ing distinct subtypes that differ in underlying pathophysiol- ogy, clinical presentation, and response to treatment. On the basis of cystoscopic findings, two IC/BPS sub-phenotypes have been described. • Patients with Hunner’s lesions are classified as having a bladder-centric IC/BPS phenotype, accounting for approximately 20% of cases. This subtype is character - ized by chronic inflammatory changes, including mast cell and lymphocyte infiltration, and typically presents with focal bladder pain and visible mucosal lesions on cystoscopy. Patients often demonstrate significant symp- tom improvement following lesion-directed therapies such as fulguration, resection, or intralesional steroid injection. • Patients without Hunner’s lesions are classified as having a non–bladder-centric IC/BPS phenotype, accounting for approximately 80% of cases. This subtype is more com- monly associated with systemic pain disorders, including fibromyalgia, endometriosis, depression, irritable bowel syndrome, vulvodynia, dyspareunia, and migraine. It is thought to involve heightened nociception and central sensitization rather than localized bladder inflamma- tion. Multimodal pain management is essential. Treat- ment options include oral pharmacotherapy—such as pentosan polysulfate sodium, hydroxyzine, amitriptyline, and pregabalin—with or without adjunctive intravesical therapies, including hyaluronic acid. Particular emphasis is placed on neuromodulatory approaches (e.g., antide- pressants and antiepileptics), as well as non-pharmaco- logical interventions such as transcutaneous electrical nerve stimulation (TENS), meditation, and structured physiotherapy with pelvic floor rehabilitation. Notably, Chung et al. were among the first investigators to describe the association between interstitial cystitis/blad- der pain syndrome (IC/BPS) and endometriosis [38]. This observation led Chung to coin the term “evil twin syndrome” to denote the coexistence of these two conditions. These patients are significantly more likely to carry a non-blad- der centric IC/BPS phenotype as well as several comorbid, systemic pain diagnoses [39]. Evidence from the literature suggests that this association is particularly pronounced in women with chronic pelvic pain. Reported prevalence rates of coexistence range from 15.5% to 78.3%, reflecting sub- stantial heterogeneity in the individual prevalence of each condition across studies [31]. This variability is largely attributable to differences in diagnostic criteria, the absence of standardized definitions for IC/BPS, and selection biases inherent in study populations. Similarly, the true prevalence of endometriosis remains uncertain due to underdiagnosis, diagnostic delays, and variability in surgical and histopatho- logical assessment. Consequently, precise epidemiological data on the coexistence of these conditions remain inconsist- ent, hindering accurate prevalence estimates and delaying the development of integrated management strategies. This gap underscores the need for well-designed prospective stud- ies to clarify their true association and clinical impact. Interstitial cystitis/bladder pain syndrome (IC/BPS), much like endometriosis, is characterized by a substantial diagnostic delay [39]. Driscoll et al. reported a median symptom duration of 5 years prior to diagnosis, with many patients initially presenting with isolated symptoms that gradually evolve into a more complex clinical picture [40]. This delay has important consequences. Women are fre- quently subjected to serial medical and surgical interven- tions, sometimes including hysterectomy, with limited ben- efit for persistent pain. In many cases, what is interpreted as refractory endometriosis may, in fact, reflect unrecognized IC/BPS. The presence of endometriosis should not exclude the possibility of concomitant bladder pathology. International Urogynecology Journal In our opinion, concomitant diagnostic cystoscopy during endometriosis surgery should not be considered routine for all patients. Rather, cystoscopy may be particularly valuable in selected clinical scenarios, including refractory lower uri- nary tract symptoms in the absence of infection, unexplained hematuria, or radiological suspicion of bladder infiltration or involvement. In these situations, cystoscopy may help identify coexisting IC/BPS, characterize bladder pheno- types, and detect bladder-penetrating endometriotic lesions, thereby supporting individualized, mechanism-based man- agement. Direct visualization and histological confirmation of endometriosis, together with objective cystoscopic assess- ment of IC/BPS phenotypes, offer an opportunity to better characterize overlapping pain mechanisms. Distinguishing bladder-centric from non–bladder-centric phenotypes may be relevant for guiding individualized therapy, although cur- rent evidence suggests that most patients with concomitant endometriosis and IC/BPS belong to the non–bladder-centric phenotype associated with systemic pain amplification and central sensitization. Routine bladder biopsies are unlikely to be necessary and should be reserved for selected cases with suspicious findings. Moreover, clinicians must recognize that pelvic surgery itself may influence bladder physiology, requiring careful interpretation of postoperative symptoms. The clinical implications are substantial. Failure to iden- tify coexisting bladder pathology or IC/BPS in appropriately selected women undergoing surgery for endometriosis may contribute to persistent postoperative pain, repeated inter - ventions, and escalating therapeutic frustration. Recognizing coexistence earlier could prevent unnecessary procedures and support a shift toward mechanism-based, multidiscipli- nary care. Although prospective data remain limited and universally accepted diagnostic criteria for IC/BPS are still evolving, the currently available evidence does not support routine cystos- copy with hydrodistension in all surgical cases of endome- triosis. Rather, they highlight the urgent need for integrated diagnostic algorithms and collaborative care models. Ulti- mately, improving recognition of the endometriosis–IC/BPS overlap is not merely a diagnostic refinement—it is a neces- sary step toward reducing pain chronification, minimizing avoidable interventions, and improving long-term quality of life for women with chronic pelvic pain. Future prospective studies are needed to determine whether selective intraoperative cystoscopy changes long- term outcomes, improves pain control, or modifies thera- peutic strategies in women with overlapping endometriosis and IC/BPS phenotypes. Until stronger evidence becomes available, a phenotype-driven and multidisciplinary approach appears more appropriate than universal cysto- scopic screening. Author’s Contribution GF, FZ, MZ: Manuscript design and writing. TP, TS: Literature search and manuscript review. IM-H: Manuscript review. Funding Open Access funding enabled and organized by Projekt DEAL. Declarations Conflicts of Interest None. Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

1. International Working Group of AAGL, ESGE, ESHRE and WES, Tomassetti C, Johnson NP, Petrozza J, Abrao MS, Einarsson JI, et al. An international terminology for endometriosis, 2021. Hum Reprod Open. 2021;2021(4):hoab029. 2. Xu S, Zhang Y, Ye P, Huang Q, Wang Y, Zhang Y, et al. Global, regional, and national burden of endometriosis among women of childbearing age from 1990 to 2021: a cross-sectional anal- ysis from the 2021 global burden of disease study. Int J Surg. 1990;111(9):5927–40. 3. - ACOG Committee on Practice Bulletins. Gynecology ACOG practice bulletin no. 11: medical management of endometriosis. Obstet Gynecol. 1999;94:1–14. 4. Sircus SI, Sant GR, Ucci AA. Bladder detrusor endometriosis mimicking interstitial cystitis. Urology. 1988;32:339–42. 5. Haas D, Shebl O, Shamiyeh A, Oppelt P. The rASRM score and the Enzian classification for endometriosis: their strengths and weaknesses. Acta Obstet Gynecol Scand. 2013;92(1):3–7. 6. Keckstein J, Saridogan E, Ulrich UA, Sillem M, Oppelt P, Schweppe KW, et al. The #Enzian classification: a comprehensive non-invasive and surgical description system for endometriosis. Acta Obstet Gynecol Scand. 2021;100(7):1165–75. 7. Montanari E, Bokor A, Szabó G, Kondo W, Trippia CH, Malzoni M, et al. Comparison of #Enzian classification and revised Ameri- can Society for Reproductive Medicine stages for the descrip- tion of disease extent in women with deep endometriosis. Hum Reprod. 2022;37(10):2359–65. 8. Hofbeck L, Au K, Blum S, Sipulina N, Lotz L, Lermann JH, et al. Clinical characterization of endometriosis phenotypes. Arch Gynecol Obstet. 2025;312(6):2089–100. https:// doi. org/ 10. 1007/ s00404- 025- 08191-4. 9. Bafort C, Dancet E, Mellaerts J, Meuleman C, Tomassetti C. Correlation between surgical phenotype and pain improve- ment after endometriosis surgery. J Minim Invasive Gynecol. 2024;31(5):453-463.e4. International Urogynecology Journal 10. Keckstein J, Hudelist G. Classification of deep endometriosis (DE) including bowel endometriosis: from r-ASRM to #Enzian-classi- fication. Best Pract Res Clin Obstet Gynaecol. 2021;71:27–37. 11. Kupka MS, Chambers GM, Dyer S, Zegers-Hochschild F, de Mouzon J, Ishihara O, et al. International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016. Fertil Steril. 2015;122(5):875–93. 12. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009. 13. Zeppernick F, Balimuttajjo S, Schorr C, Sibelius F, Schuler M, Harth S, et al. Non-invasive diagnosis of endometriosis by questionnaires in patients using contraception. J Clin Med. 2025;15(1):30. 14. Gaia-Oltean AI, Boitor D, Pop LA, Galea G, Telecan T, Micu R. Non-invasive methods for early diagnosis of endometriosis- a comprehensive narrative literature review. Healthcare (Basel). 2025;13(24):3276. 15. Falsetta ML, Chrysilla E. Current understanding of endometrio- sis pathophysiology and future perspectives. Semin Reprod Med. 2025;43(3):167–79. 16. Alotaibi FT. Pathophysiology of endometriosis: insights from immunohistochemical analysis of ectopic and eutopic tissues. Int J Mol Sci. 2025;26(13):5998. 17. Mariadas H, Chen JH, Chen KH. The molecular and cellular mechanisms of endometriosis: from basic pathophysiology to clinical implications. Int J Mol Sci. 2025;26(6):2458. 18. Sadłocha M, Toczek J, Major K, Staniczek J, Stojko R. Endome- triosis: molecular pathophysiology and recent treatment strate- gies-comprehensive literature review. Pharmaceuticals (Basel). 2024;17(7):827. 19. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V. Patho- genesis of endometriosis: the genetic/epigenetic theory. Fertil Steril. 2019;111:327–40. 20. McCallion A, Falconer H, Widschwendter M, Horne AW. Estro- gen mediates inflammatory role of mast cells in endometriosis pathophysiology. Front Immunol. 2022;13:961599. 21. Oală IE, Dumitrescu LS, Mihu CM, Gluhovschi A, Manea M, Nemeti G, et al. Endometriosis and the role of pro-inflammatory and anti-inflammatory cytokines in pathophysiology: a narrative review of the literature. Diagnostics. 2024;14:312. 22. Lamceva J, Uljanovs R, Strumfa I. The main theories on the pathogenesis of endometriosis. Int J Mol Sci. 2023;24:4254. 23. Juganavar A, Joshi KS. Chronic pelvic pain: a comprehensive review. Cureus. 2022;14(10):e30691. 24. Ahangari A. Prevalence of chronic pelvic pain among women: an updated review. Pain Physician. 2014;17(2):E141-7. 25. Latthe P, Latthe M, Say L, Gülmezoglu M, Khan KS. WHO sys- tematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity. BMC Public Health. 2006;6:177. 26. American College of Obstetricians and Gynecologists. ReVitalize. Gynecology Data Definitions; American College of Obstetric and Gynecology (ACOG): Washington, DC, USA, 2018. 27. Huang G, Le A-L, Goddard Y, James D, Thavorn K, Payne M, et al. A systematic review of the cost of chronic pelvic pain in women. J Obstet Gynaecol Can. 2022;44:286-293.e3. 28. Reiter RC. A profile of women with chronic pelvic pain. Clin Obstet Gynecol. 1990;33(1):130–6. 29. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55:377–91. 30. Kaya S, Hermans L, Willems T, Roussel N, Meeus M. Litera- ture review central sensitization in urogynecological chronic pelvic pain: a systematic literature review. Pain Physician. 2013;16:291–308. 31. Inzoli A, Barba M, Costa C, Carazita V, Cola A, Fantauzzi M, et al. The evil twins of chronic pelvic pain syndrome: a systematic review and meta-analysis on interstitial cystitis/painful bladder syndrome and endometriosis. Healthcare (Basel, Switzerland). 2024;12:2403. 32. As-Sanie S, Ross WT, Till SR. Evaluation and treatment of chronic pelvic pain. Obstet Gynecol. 2026;147(1):21–43. 33. Fall M, Baranowski AP, Elneil S, Engeler D, Hughes J, Mes- selink EJ, et al. EAU guidelines on chronic pelvic pain. Eur Urol. 2010;57:35–48. 34. Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185(6):2162–70. 35. International Continence Society. Terminology discussion: Inter- stitial Cystitis/Bladder Pain Syndrome (IC/BPS) [Internet]. [cited 2025 Jul 29]. Available from: https:// www. ics. org/ commi ttees/ stand ardis ation/ termi nolog ydisc ussio ns/ icbps 36. Engeler D. European Association of Urology. Guidelines on Blad- der Pain Syndrome/Interstitial Cystitis. 2024. https:// uroweb. org/ guide lines/ chron ic- pelvic- pain. 37. Yu W-R, Jhang J-F, Jiang Y-H, Kuo H-C. The pathomechanism and current treatments for chronic interstitial cystitis and bladder pain syndrome. Biomedicines. 2024;12:2051. 38. Chung MK, Chung RR, Gordon D, Jennings C. The evil twins of chronic pelvic pain syndrome: endometriosis and interstitial cystitis. JSLS. 2002;6(4):311–4. 39. Overholt TL, Evans RJ, Lessey BA, Matthews CA, Hines KN, Badlani G, et al. Non-bladder centric interstitial cystitis/bladder pain syndrome phenotype is significantly associated with co- occurring endometriosis. Can J Urol. 2020;27(3):10257–62. 40. Driscoll A, Teichman JM. How do patients with interstitial cystitis present? J Urol. 2001;166:2118–20. 41. O’Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich- Kroll J. The interstitial cystitis symptom index and problem index. Urology. 1997;49(5A Suppl):58–63. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.