Antonella Giannantoni
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Abbreviations |
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BPS/IC |
Bladder pain syndrome-interstitial cystitis |
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CEDS |
Center for Epidemiologic Studies Depression Scale |
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DMSO |
Dimethyl sulfoxide |
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FSFI |
Female Sexual Function Index |
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ICPI |
Interstitial Cystitis Problem Index |
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ICSI |
Interstitial Cystitis Symptom Index |
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MCS |
Mental Composite Scale |
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MGP |
McGill Pain |
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QoL |
Quality of Life |
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PSS |
Perceived Stress Scale |
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PUF |
Pelvic Pain and Urgency/Frequency Questionnaire |
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STAI |
State-Trait Anxiety Inventory |
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UPOINT |
Urinary Psychosocial, Organ Specific, Infection, Neurologic or Systemic, and Tenderness |
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VAS |
Visual Analogue Scale |
14.1 Introduction
BPS/IC is a chronic disorder diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder accompanied by at least one urinary symptom such as persistent urge to void or urinary frequency [10, 45]. The etiology is still unclear, and different factors have been retained to be the cause of the disease, as infections, autoimmunity, mucosal abnormalities, urinary toxins, and local neuronal dysfunction [1]. None have persuasively explained the syndrome, and the lack of understanding of its pathogenesis has led to empiric and often inadequate therapies [47]. Due to many different clinical presentations, it is retained that patients with BPS/IC do not represent a homogenous group with perceived bladder pain associated with urinary frequency and urgency, but rather a group of individual patients with widely differing clinical phenotypes [22].
Sexual dysfunction symptoms have been reported for women with disorders related to BPS/IC, including lack of libido and of sexual interest, pain during intercourse, and vulvodynia [1].
The knowledge that sexual dysfunction may be present in patients with BPS/IC and can contribute to a reduced Quality of Life (QoL) has been only recently acquired.
14.2 Epidemiology
Research has found significantly worse sexual functioning among patients with BPS/IC than among the general population or age-matched control patients for several different sexual functioning domains, including a lack of desire, reduced arousal, lubrication difficulties, low orgasm frequency, dissatisfaction, and pain [25, 28].
The exact prevalence of sexual dysfunction among women with BPS/IC is unknown. When comparing prevalence rates of sexual dysfunction between women in the general population in the United States and those affected by the diseases, it was observed that about 40 % of women in the general population have reported at least one sexual dysfunction, such as a lack of interest (31 %), arousal difficulties (19 %), inability to achieve orgasm (25 %), performance anxiety (12 %), pain (15 %), and lack of pleasure (23 %) [7, 11, 14, 16, 39]. In convenient samples of women with BPS/IC, the range of dysfunction across studies has been found to range between 13 and 87 % ([21, 27, 29, 30, 42]). The results of the RICE study, the first population-based representative sample of women with BPS/IC symptoms, showed that women with the disease experience very high levels of sexual dysfunction compared with the general population.
In a previous study from Bogart et al., 88 % of women with a current partner complained of >1 general sexual dysfunction symptom in the previous 4 weeks, and 90 % of those with a current partner reported any BPS/IC -specific sexual dysfunction symptoms during the same period [2]. A lack of sexual interest and bladder pain during and/or after sex were the most prevalent symptoms, experienced by about two thirds of the women [2]. In a mailed survey sent to 5000 randomly selected women from the United States and 407 women with BPS/IC from a large referral center, a significantly greater proportion of patients (67.2 %) than controls (18 %) reported having pelvic pain during intercourse [29, 30]. Fear of having pain during sexual intercourse was reported significantly more by 108 cases of 215 than controls 111 of 823 (p = 0.001), and in those having intercourse, dyspareunia was reported more by the 132 cases of 177 than controls 193 of 646 (p = 0.001) [29, 30]. Before the BPS/IC diagnosis, 86 % of cases recalled having moderate to high sexual desire compared with 78 % of the controls (p = 0.016). After the BPS/IC diagnosis, sexual desire in cases with moderate-high severity of the disease declined from 86 to 40 %. The percentage of BPS/IC patients reporting orgasm as frequently or very frequently was lower (44 % among the cases). Interestingly, in this study, women with BPS/IC had significantly more pain and fear of pain during intercourse even in adolescence [29, 30].
Many studies reported that sexual pain in BPS/IC patients is a strong predictor of poor QoL [23] and that up to 54 % of these patients avoid intercourse with their partners most of the time [49]. In a recent case-control study, comparing 554 patients with BPS/IC and 131 controls, patients reported significant sexual dysfunction in all domains of the FSFI, with pain as the most significant finding [53]. Alterations in arousal, lubrication, and pain were most notable in patients younger than 30 years, while patients older than 50 experienced less distress in relation to their sexual dysfunction caused by BPS/IC [29, 30, 53]. In a survey of 565 patients with BPS/IC, more patients reported that their pain localized to the vaginal area (60.8 %), than to the lower abdominal (56.7 %) or suprapubic region (53.2 %) [13]. Over a third of patients also reported experiencing pain for days after intercourse [13].
14.3 Risk Factors
Sexual abuse. Almost no research has been conducted regarding the risk factors for sexual dysfunction among women with BPS/IC or whether women with BPS/ IC receive medical help for sexual dysfunction issues. In a study of chronic pelvic pain and its relationship to prior sexual or physical abuse, subjects with a history of abuse reported more severe pain intensity compared to those without prior abuse even when there was no apparent objective medical basis for the difference in pain intensity [17]. In the study of Seth and Teichman [38], the subjects with BPS/IC with a sexual abuse history score worse on multiple FSFI domains and exhibited more tender areas on the abdominal and pelvic floor examination compared to those with PBS/IC without a history of abuse. Increased rates of adult chronic pain in patients with prior sexual abuse persist even after controlling for concurrent depression [3]. It is thought that sexual traumatization leads to dys- regulation in the hypothalamic-pituitary-adrenal axis and increased autonomic activation. If prior sensitization of these central pathways occurs from sexual traumatization, patients with subsequent PBS/IC might have a more easily upregu- lated central nervous system compared to those without such prior sensitization [38]. A recent study reported that 18-33 % of patients with PBS/IC have a history of sexual abuse [29, 30].
14.3.1 Psychological Status: Anxiety and Depression
Several somatic and psychological predictors are associated with poorer BPS/IC QoL. In previous epidemiological studies, 55.8 % of BPS/IC patients presented with depression and 29.8 % showed feelings of worthlessness or helplessness. In these patients, depressive state has been found to be associated with maladjusted coping strategies for self-managing pain such as catastrophizing [43]. Catastrophizing is defined as the tendency to mentally focus on pain and evaluate one’s ability to manage pain negatively [41]. Catastrophizing affects the QoL and reported pain severity of male and female patients with chronic pelvic pain [35]. Pain and reduced sexual functioning have been observed to be associated with poorer psychological functioning in other chronic pain conditions [6, 48]. Nickel et al. found that sexual functioning was the only predictor of poorer mental QoL in BPS/IC patients [23]. In a previous study from Tripp et al. [43], helplessness catastrophizing was associated with reduced MCS QoL more than the other independent variables. In addition, a high level of association between depression and MCS QoL was identified, suggesting that these constructs are basically assessing the same domain. From a medical perspective, focused assessments of psychological and medical predictors before treatment may be helpful. Identifying catastrophizing could help physicians in selecting the most efficient treatment, particularly the adjunctive treatment of patients with a cognitive behavioral intervention. From a neurophysiological point of view, chronic inflammation induces pain following chronic changes in neurotransmission, mechanisms of pain control, and tissue responses. These stimulatory factors affect the mechanisms associated with pain. A persistent presence of these stimulations converts the pelvic pain to neurological pain (which eventually leads to chronic pain syndrome) contributing to the impairment of sexual function [9].
14.3.2 Etiopathogenesis of Sexual Pain
Dyspareunia in association with BPS/IC may have a variety of causes. Resistance to penetration resulting from fear of pain may cause pelvic floor hypertonus, restricting vaginal entry and both dyspareunia and mechanical trauma of the vestibular mucosa and urethra [9]. Mechanical irritation of the urethra and/or bladder during intercourse may cause discomfort and exacerbate symptoms of PBS/IC. The pelvic floor and the bladder share common nerve pathways which may also result in shared symptoms. During sexual intercourse, physical irritation to the urethra and urinary bladder causes discomfort and increases the symptoms of BPS/IC.
14.4 Clinical Presentation
Sexual pain or dyspareunia, which is pain experienced during or after intercourse, may be due to an organic or psychological factor [37]. BPS/IC is a potential cause of sexual pain and should be considered in the differential diagnosis of dyspareunia.
Women with BPS/IC may present with the combination of dyspareunia and chronic pelvic pain as chief complains or the symptom of sexual pain can be discovered by the healthcare physician during the history. In a survey of 138 patients with BPS/IC, dyspareunia has been reported by 51 % with a larger proportion (79 %) indicating that sexual intercourse increased their pain [48]. Patients with BPS/IC and sexual dysfunction cannot be easily recognized, particularly in the early stages of the disease. The combination of chronic pelvic pain with urinary symptoms, as increased daytime and nighttime frequency and urgency, associated with vulvar pain or dyspareunia, are the typical presentation picture. Although patients with BPS/IC often present with only one symptom and may not develop the full spectrum of symptoms for several years, more typically symptoms present in a pattern of recurrences followed by remissions, with a gradual progression to a more severe condition along time [51]. In a previous study, 40.3 % of patients with BPS/IC presented with urinary incontinence during sexual intercourse [52]. Considering that BPS/IC patients present with different clinical phenotypes, multiple aspects of the disease should be considered in the clinical presentation and in the therapeutic program for these patients. Nickel et al. developed the UPOINT system to categorize the phenotype of BPS/IC patients into six clinically identifiable domains [22]. It was observed that the number of positive UPOINT domains significantly correlated with the severity of BPS/IC symptoms, as measured using the ICSI questionnaire and pain VAS scores. The UPOINT system does not include a sexual domain, although sexual pain is present in 88 % of patients with BPS/IC. Recently, Liu et al. demonstrated that sexual dysfunction is an important component of BPS/IC phenotype, and adding a sexual dysfunction domain to the UPOINT system improves the association with BPS/IC symptom severity [15]. BPS/IC may be the sole cause of symptoms or occur concurrently with other causes such as endometriosis or myofascial pain [4].
Endometriosis is a common cause of chronic pelvic pain in women and is diagnosed in up to 80 % of these patients. However, increasing evidence suggests that endometriosis in BPS/IC patients with chronic pelvic pain is more prevalent than was previously thought and may play a significant role in the cause of the disease. Symptoms commonly associated with endometriosis include perimenstrual lower abdominal pain and dyspareunia. In addition, patients with endometriosis can also present with dysuria, hematuria, urinary frequency, and painful voiding, particularly if the bladder is involved. When therapy for the symptoms of endometriosis is unsuccessful, it may be thought that BPS/IC may be an underlying cause [4].
Other common differential diagnoses for sexual pain due to BPS/IC are vaginismus, vulvar vestibulitis, vulvodynia, atrophic tissue or impaired lubrication, adnexal pathology, chronic cervicitis, pelvic inflammatory disease, and urethra disorders.
14.5 Diagnosis
The baseline evaluation includes history and physical and laboratory examination in order to assess the presence of BPS/IC and exclude other diseases with similar symptoms. Urinary symptoms and pain level should be adequately investigated and assessed. Pain body maps can be used in patients whose presentation suggests a more global pain syndrome [10]. Most important, any eventual confusable disease should be diagnosed and excluded. In this respect, infection, bladder stone, bladder neck obstruction, overactive bladder, carcinoma of the bladder, endometriosis, urogenital prolapse, and cervical, uterine, and ovarian cancer have to be excluded with appropriate investigations [45]. One crucial point is an appropriate patient’s symptom evaluation. It is important to have a uniform and reliable method to evaluate symptoms, and, in this regard, the use of standardized questionnaires is of extreme usefulness.
14.5.1 Condition-Specific Symptom Questionnaires
ICSI and ICPI questionnaires. These questionnaires have been designed to capture the most important voiding and pain symptoms and to assess how patients find them in the clearest and most concise manner possible [24]. Both instruments have been designed and validated for self-administration, so that trained interviewers are not needed to use them. Psychometric performance of both instruments is good, with the symptom index demonstrating excellent ability to discriminate characteristics between patients and controls [31].
MPQ questionnaire. Also in a more recent short form, this questionnaire provides quantitative information that can be used statistically, and it appears sufficiently sensitive to detect differences among different methods to relieve pain. It measures functional physical component status and mental component status [18, 19]. The MPQ has been used in the assessment of multiple types of acute and chronic pain, and its reliability and validity have been extensively documented.
PUF questionnaire. It is a symptom scale that gives balanced attention to urinary urgency/frequency, pelvic pain, and symptoms associated with sexual intercourse [26].
14.5.2 Psychosocial Parameters
Depressive symptoms can be assessed using the CES-D [32] and anxiety symptoms with the Trait Anxiety Scale of the STAI [40].
The PSS can be used to assess stress [5] and the FSFI is used to measure sexual functioning [34]. The Pain Catastrophizing Scale is used to measure catastrophizing cognitions concerning pain [41].
General questionnaires focused on sexual function include the FSFI and Sexual History Form 12, which were specifically designed to evaluate sexual function [34, 46]. These questionnaires have undergone validation and reliability testing in a general population. Although FSFI questionnaire provides overall metric and specific subscales of sexual functioning, including sexual pain, it is not condition specific and may not be sensitive enough to detect differences due to BPS/IC.
Quality-of-Life Questionnaires, such as the King’s Health Questionnaire and the Incontinence Impact Questionnaire [33, 44], include a few questions addressing sexual function but really deal with the overall impact of incontinence and/or prolapse on the patient’s QoL or well-being and do not focus on sexual function.
14.6 Management Strategies for Patients with BPS/IC and Sexual Pain
According to some studies, treatment of patients with PBS/IC results in improved sexual function and quality of life. Nickel et al. reported that sexual function was the key factor in determining the quality of life in elderly patients with the disease [23]. The authors also suggested the goal of treatment should focus on sexual dysfunction and that the improvement of symptoms of PBS/IC should accompany improvement in sexual function. In patients with sexual dysfunction presenting with BPS/IC, treatment should be approached in many directions, including psychological and social aspects. Patients should be educated that BPS/IC is a chronic condition associated with relapsing and remission phases and that improvement usually occurs gradually. It is important to schedule regular follow-up visit thus giving the patient a sense of attention and more comprehensive cure. As the etiology of the disease appears to be multifactorial, a multimodal approach seems to be more appropriate.
Dietary modification may be useful to reduce symptoms in many patients. There are several “trigger foods” that can vary for each individual patients and a “food diary” is an important tool to use during an elimination diet. It will help the patient keep track of what he/she is eating and determine reaction to specific foods and beverages and whether there is an allergy or a sensitivity. Alcohol, artificial sweeteners (aspartame and saccharin), coffee, citrus juices, cranberry juice, hot peppers, soda, and spicy foods are the most bothersome foods for people with BPS/ IC. Changes in diet and lifestyle can help reduce symptoms, and bladder retraining my reduce voiding frequency in some patients with the disease. When the patients’ symptoms do not respond to nonpharmacological treatment, it is necessary to move toward pharmacological interventions, which often should be given as a combination of drugs. A combination of oral and intravesical therapies together with lifestyle intervention and physical therapy can gradually improve pain and urinary symptoms in patients affected by BPS/IC. Early treatment intervention may prevent the progression of the disease to more severe stages, when tissue damage is permanent and the BPS/IC became a chronic condition.
14.6.1 Self-Care for Patients with BPS/IC and Sexual Pain
There are many self-care approaches that can help women and their partners achieve some levels of sexual intimacy and give her a sense of control over her sexual life. Alternatives to sexual intercourse or different coital positions, assuming drugs to relax pelvic muscles before intercourse, may help to reduce pain during sexual activity. Patients should keep a bladder diary to record any triggers for symptom flares. In addition they should note any event which is linked to symptom exacerbations. Vaginal lubricants could be useful in reducing dyspareunia due to friction to the urethra. Precoital or postcoital voiding or the use of ice packs to the suprapubic area or genitalia can alleviate pain symptoms during or after intercourse [51].
14.6.2 Pharmacological Treatment
Several pharmacological agents have been used in the treatment of patients with BPS/IC. Only few of these drugs have been approved by the Food and Drug Administration, as pentosan polysulfate sodium orally given or intravesical DMSO. Other oral or intravesical agents may be used “off label.” Nickel et al. conducted a study in 128 patients who underwent medical treatment with oral pentosan polysulfate 300 mg/day for 32 weeks [21]. Patients reported statistically significant improvements in pain and in sexual functioning scores after treatment, and symptom improvement was moderately related with improvements in sexual dysfunction. Similar results were observed by Hung et al., who treated patients with BPS/ IC and sexual dysfunction with intravesical hyaluronic acid solution [12]. In their study, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire total scores improved significantly from baseline after 1 month and 6 months of treatment [12].
Welk et al. treated 23 sexually active patients with BPS/IC with an intravesical solution constituted by lidocaine, bicarbonate, and heparin [50]. All patients completed the Pelvic Pain Urgency Frequency symptom scale, voiding diary and the pain domain (questions 17-19) of the FSFI questionnaire before and after therapy. Intravesical instillations were repeated 3 times weekly for 3 weeks. Of the 23 patients, 13 (57 %) reported resolution of dyspareunia. The results of this study demonstrated that an intravesical multidrug solution provides relief of voiding symptoms, pain, and dyspareunia in patients with BPS/IC. In a prospective case- control study conducted in a tertiary referral center, 69 patients with BPS/IC were treated applying determined therapeutical steps including tetracycline, bladder instillation consisting of heparin, local anesthetic and natrium-bicarbonate, prednisolone and antihistaminics, or instillation with DMSO [36]. Pain, nocturia, and urinary frequency and urgency were significantly reduced after treatment. The King’s Health Questionnaire showed a significant improvement of all domains but emotions and sleep, and FSFI improved significantly in all domains but orgasm [36]. Recently, Nickel et al. proposed the use of flexible therapeutic strategy for patients referred to a specialized BPS/IC clinic using an individualized phenotype- directed treatment plan based on clinically based UPOINT categorization [20]. They found that almost 50 % of patients, regardless of the complexity or severity of condition, experienced clinically significant improvement using an individualized phenotype-directed therapeutic approach [20].
Other studies proposed many kinds of different approaches, but, because of the paucity of randomized placebo-controlled studies on different treatments, an evidence-based management approach has not yet been developed [8], and limited evidence exists for the few treatments for BPS/IC. The lack of definitive conclusions is due to the great heterogeneity in methodology, symptom assessment, duration of treatment, and follow-up in both RCTs and nRCTs. In addition, few of the previously published studies considered specifically improvements in sexual activity after treatment.
Conclusions
Sexual dysfunction is a common symptom in women affected by BPS/IC, but it has been only recently recognized, although it highly affects the QoL of patients. Prompt recognition and intervention of BPS/IC are a determinant factor for a successful treatment in these women, in order to alleviate both pain and sexual dysfunction.
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