Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Alfuzosin and symptoms of chronic prostatitis-chronic pelvic pain syndrome.

BACKGROUND: In men with chronic prostatitis-chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis-chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score. RESULTS: A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, -11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P=0.90). The rates of adverse events in the two groups were also similar. CONCLUSIONS: Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis-chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. (ClinicalTrials.gov number, NCT00103402.)

Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States.

PURPOSE: Bladder pain syndrome/interstitial cystitis is a poorly understood condition that can cause serious disability. We provide the first population based symptom prevalence estimate to our knowledge among United States adult females. MATERIALS AND METHODS: We developed and validated 2 case definitions to identify bladder pain syndrome/interstitial cystitis symptoms. Beginning in August 2007 we telephoned United States households, seeking adult women with bladder symptoms or a bladder pain syndrome/interstitial cystitis diagnosis. Second stage screening identified those subjects who met case definition criteria. Each completed a 60-minute interview on the severity and impact of bladder symptoms, health care seeking and demographics. Data collection ended in April 2009. Using population and nonresponse weights we calculated prevalence estimates based on definitions spanning a range of sensitivity and specificity. We used United States Census counts to estimate the number of affected women in 2006. The random sample included 146,231 households, of which 131,691 included an adult female. Of these households 32,474 reported an adult female with bladder symptoms or diagnosis, of which 12,752 completed the questionnaire. RESULTS: Based on the high sensitivity definition 6.53% (95% CI 6.28, 6.79) of women met symptom criteria. Based on the high specificity definition 2.70% (95% CI 2.53, 2.86) of women met the criteria. These percentages translated into 3.3 to 7.9 million United States women 18 years old or older with bladder pain syndrome/interstitial cystitis symptoms. Symptom severity and impact were comparable to those of adult women with established diagnoses. However, only 9.7% of the women reported being assigned a bladder pain syndrome/interstitial cystitis diagnosis. CONCLUSIONS: Bladder pain syndrome/interstitial cystitis symptoms are widespread among United States women and associated with considerable disability. These results suggest bladder pain syndrome/interstitial cystitis may be underdiagnosed.

AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome.

PURPOSE: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS: The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

Early termination of a trial of mycophenolate mofetil for treatment of interstitial cystitis/painful bladder syndrome: lessons learned.

PURPOSE: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries. RESULTS: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls. CONCLUSIONS: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.

Burch colposuspension versus fascial sling to reduce urinary stress incontinence.

BACKGROUND: Many surgical procedures are available for women with urinary stress incontinence, yet few randomized clinical trials have been conducted to provide a basis for treatment recommendations. METHODS: We performed a multicenter, randomized clinical trial comparing two procedures--the pubovaginal sling, using autologous rectus fascia, and the Burch colposuspension--among women with stress incontinence. Women were eligible for the study if they had predominant symptoms associated with the condition, a positive stress test, and urethral hypermobility. The primary outcomes were success in terms of overall urinary-incontinence measures, which required a negative pad test, no urinary incontinence (as recorded in a 3-day diary), a negative cough and Valsalva stress test, no self-reported symptoms, and no retreatment for the condition, and success in terms of measures of stress incontinence specifically, which required only the latter three criteria. We also assessed postoperative urge incontinence, voiding dysfunction, and adverse events. RESULTS: A total of 655 women were randomly assigned to study groups: 326 to undergo the sling procedure and 329 to undergo the Burch procedure; 520 women (79%) completed the outcome assessment. At 24 months, success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both the overall category of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence (66% vs. 49%, P<0.001). However, more women who underwent the sling procedure had urinary tract infections, difficulty voiding, and postoperative urge incontinence. CONCLUSIONS: The autologous fascial sling results in a higher rate of successful treatment of stress incontinence but also greater morbidity than the Burch colposuspension. (ClinicalTrials.gov number, NCT00064662 [ClinicalTrials.gov] .).

Development, validation and testing of an epidemiological case definition of interstitial cystitis/painful bladder syndrome.

PURPOSE: No standard case definition exists for interstitial cystitis/painful bladder syndrome for patient screening or epidemiological studies. As part of the RAND Interstitial Cystitis Epidemiology study, we developed a case definition for interstitial cystitis/painful bladder syndrome with known sensitivity and specificity. We compared this definition with others used in interstitial cystitis/painful bladder syndrome epidemiological studies. MATERIALS AND METHODS: We reviewed the literature and performed a structured, expert panel process to arrive at an interstitial cystitis/painful bladder syndrome case definition. We developed a questionnaire to assess interstitial cystitis/painful bladder syndrome symptoms using this case definition and others used in the literature. We administered the questionnaire to 599 women with interstitial cystitis/painful bladder syndrome, overactive bladder, endometriosis or vulvodynia. The sensitivity and specificity of each definition was calculated using physician assigned diagnoses as the reference standard. RESULTS: No single epidemiological definition had high sensitivity and high specificity. Thus, 2 definitions were developed. One had high sensitivity (81%) and low specificity (54%), and the other had the converse (48% sensitivity and 83% specificity). These values were comparable or superior to those of other epidemiological definitions used in interstitial cystitis/painful bladder syndrome prevalence studies. CONCLUSIONS: No single case definition of interstitial cystitis/painful bladder syndrome provides high sensitivity and high specificity to identify the condition. For prevalence studies of interstitial cystitis/painful bladder syndrome the best approach may be to use 2 definitions that would yield a prevalence range. The RAND Interstitial Cystitis Epidemiology interstitial cystitis/painful bladder syndrome case definitions, developed through structured consensus and validation, can be used for this purpose.

Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome.

PURPOSE: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports. MATERIALS AND METHODS: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment. RESULTS: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01). CONCLUSIONS: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.

Bladder Pain Syndrome Committee of the International Consultation on Incontinence.

AIMS OF STUDY: The Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis, in a comprehensive fashion. This included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research. STUDY DESIGN, MATERIALS, METHODS: The emphasis was on new information developed since the last consultation 4 years previously. Where possible, existing evidence was assessed and a level of recommendation was developed according to the Oxford system of classification. RESULTS: The consultation decided to refer to the condition as "bladder pain syndrome" (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy. Reasonable definitions of BPS include the definition of the ESSIC European group and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS. The initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture. Urine cytology and cystoscopy are recommended if clinically indicated. Treatment progresses from conservative management through various oral and intravesical therapies, with most surgical therapies reserved for unresponsive cases. Pain management is critical throughout the treatment process. The consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder. Recommendations for future research pathways are suggested.

Urinary incontinence among women with type 1 diabetes--how common is it?

PURPOSE: We compared the prevalence, level of bother and effect on daily activities of urinary incontinence among women with type 1 diabetes enrolled in the Epidemiology of Diabetes Interventions and Complications study to a population based sample of women with normal glucose. MATERIALS AND METHODS: We performed a cross-sectional analysis of women with type 1 diabetes and normal glucose tolerance using 2 study populations. The Diabetes Control and Complications Trial cohort followup, Epidemiology of Diabetes Interventions and Complications, began in 1994. In 2004 women participants (550) completed a self-administered questionnaire on urinary incontinence. Our primary outcome was weekly or greater incontinence, overall and by type. Prevalence of urinary incontinence was compared to a subgroup of women with normal glucose in the 2001 to 2002 National Health and Nutrition Examination Survey (NHANES). RESULTS: Overall 65% of women with type 1 diabetes reported any urinary incontinence (17% reported weekly incontinence). Nearly 40% of these women were greatly bothered by their incontinence and 9% believed it affected their day-to-day activities. Women with type 1 diabetes had a nearly 2-fold greater prevalence of weekly urge incontinence compared to those without diabetes in the NHANES cohort (8.8% vs 4.5%, p = 0.01). CONCLUSIONS: Urinary incontinence is common in women with type 1 diabetes and the prevalence of weekly urge incontinence is far greater compared to that in women with normal glucose levels. Moreover, the prevalence of urinary incontinence in women with type 1 diabetes was greater than that of neuropathy, retinopathy and nephropathy. These findings highlight the importance of screening for urinary incontinence among women with type 1 diabetes. Studies examining factors associated with urinary incontinence in women with type 1 diabetes are warranted.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Challenges of conducting multi-center, multi-disciplinary urinary incontinence clinical trials: experience of the urinary incontinence treatment network.

AIMS: The Urinary Incontinence Treatment Network (UITN) was established in 2000 as a multi-disciplinary, multi-institutional network by the National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDK) to investigate treatments for urinary incontinence in women. METHODS: Over 8 years this network composed of urologists, urogynecologists, geriatricians, behavioral psychologists, physical therapists, nurses, epidemiologists, social scientists and statisticians from nine academic sites and a Data Coordinating Center has been effective in designing and completing prospective randomized clinical trials for treatments of urinary incontinence in women. RESULTS: Two major clinical trials have been completed and a third has completed recruitment. The focus of the completed trials was a comparison of surgical methods to treat stress urinary incontinence whereas the third examined the potential benefit of combined behavioral intervention and antimuscarinic drug therapy to eliminate the need for long-term use of drug therapy alone to manage urge urinary incontinence. The scientific output of the network measured by abstracts, original papers and presentations demonstrates the productivity of the network. CONCLUSIONS: Many unique challenges are posed by a multi-disciplinary team located at sites across the United States undertaking several clinical trials. This review presents some of the logistics, barriers, tactics, and strategies used to create this successful clinical trials network focused on urinary incontinence.

Redesigning a large-scale clinical trial in response to negative external trial results: the CAMUS study of phytotherapy for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the US. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern US, and extracts of the bark of Pygeum africanum, the African plum tree. PURPOSE: The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH. METHODS: CAMUS was originally designed as a 3300-participant, four-arm trial of S. repens, P. africanum, an alpha-adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that S. repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at 1 year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6-18 months) symptom relief could be achieved with increasing doses of S. repens, the phytotherapy most commonly used in the US for BPH. RESULTS: Results are anticipated in 2011. CONCLUSIONS: Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of S. repens had to be established before proceeding to a long-term clinical trial.

Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial.

BACKGROUND: Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy. OBJECTIVE: To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy. DESIGN: 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006. SETTING: 9 university-affiliated outpatient clinics. PATIENTS: 307 women with urge-predominant incontinence. INTERVENTION: 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months. MEASUREMENTS: The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment. RESULTS: 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]). LIMITATIONS: Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%. CONCLUSION: The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms.

Followup of patients with interstitial cystitis responsive to treatment with intravesical bacillus Calmette-Guerin or placebo.

PURPOSE: We evaluated the longer term response in patients with interstitial cystitis who initially responded to intravesical bacillus Calmette-Guerin or placebo in a randomized clinical trial. MATERIALS AND METHODS: Patients with interstitial cystitis who responded positively to treatment with bacillus Calmette-Guerin or placebo after 34 weeks of followup in a double-blind clinical trial were followed for an additional 34 weeks in an observational study to assess response durability. Outcomes at 68 weeks included a patient reported global response assessment, 24-hour voiding diary, and pain, urgency and validated interstitial cystitis symptom indexes. RESULTS: Of responders to bacillus Calmette-Guerin or placebo in the clinical trial 38 continued extended followup in the observational study. A total of 12 (75%) responders who received placebo and 19 (86%) who received bacillus Calmette-Guerin considered themselves to remain moderately or markedly improved at week 68. Improved symptom outcomes were also generally maintained during followup in the 2 groups. CONCLUSIONS: Most patients who respond to therapy with intravesical bacillus Calmette-Guerin or placebo maintain improved symptoms for up to 68 weeks after the initiation of therapy. However, initial response rates are low and placebo responders demonstrated essentially the same durability of response as bacillus Calmette-Guerin responders. These results argue against the routine use of bacillus Calmette-Guerin in this patient group.

Long-term treatment with finasteride results in a clinically significant reduction in total prostate volume compared to placebo over the full range of baseline prostate sizes in men enrolled in the MTOPS trial.

PURPOSE: In the present analysis we examined data from the MTOPS (Medical Therapy of Prostatic Symptoms) trial to determine the effect of long-term finasteride treatment, either alone or in combination with doxazosin, on total prostate volume across the full range of baseline total prostate volume values in men enrolled in this study. MATERIALS AND METHODS: In this trial a total of 3,047 patients with lower urinary tract symptoms were randomized to placebo, doxazosin (4 to 8 mg), finasteride (5 mg) or the combination of doxazosin and finasteride (average length of treatment 4.5 years). Total prostate volume was measured by transrectal ultrasound in all patients at baseline, yearly and at study end or at termination of participation. RESULTS: Long-term treatment with finasteride led to a consistent reduction of approximately 25% in total prostate volume compared to placebo in men with a relatively small prostate (less than 25 to 30 ml), as well as in those with a moderate size (30 to less than 40 ml) or enlarged prostate (40 ml or greater) at baseline. CONCLUSIONS: In this MTOPS data analysis long-term (more than 4 years) treatment with finasteride, either alone or in combination with doxazosin, led to a consistent, clinically significant reduction in total prostate volume compared to placebo in patients with lower urinary tract symptoms and benign prostatic hyperplasia whose baseline prostate size ranged from relatively small (less than 25 to 30 ml) to enlarged (40 ml or greater).

Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To examine interactions between demographic, pain, urinary, psychological and environmental predictors of quality of life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: In all, 253 men previously enrolled in the National Institutes of Health Chronic Prostatitis Cohort study in North American tertiary-care clinical centres (six in the USA and one in Canada) self-reported with validated instruments, including the QOL subscales of the Short Form-12 (physical, SF12-PCS; and mental, SF12-MCS), demographics, urinary symptoms, depression, current pain, pain coping, 'catastrophizing' (catastrophic thinking about pain), pain control, social support and solicitous responses from a partner. Data were collected through a one-time survey. Covariates determined to be significant were entered into a multivariable regression model predicting SF12-PCS and SF12-MCS. RESULTS: Adjusting for covariates, regression models showed that poorer SF12-PCS scores were predicted by worse urinary function (P < 0.001) and increased use of pain-contingent resting as a coping strategy (P = 0.026). Further, poorer SF12-MCS scores were predicted by greater pain catastrophizing (P = 0.002) and lower perceptions of social support (P< 0.001). In separate follow-up analyses, helplessness was the significant catastrophizing subscale (P < 0.001), while support from family and friends were the significant social support subscales (P = 0.002 and <0.001). CONCLUSIONS: These data suggest that specific coping and environmental factors (i.e. catastrophizing, pain-contingent resting, social support) are significant in understanding how patients with CP/CPPS adjust. These data can be used to develop specific cognitive-behavioural programmes for men with CP/CPPS who are refractory to standard medical therapy.

Category III chronic prostatitis/chronic pelvic pain syndrome: insights from the National Institutes of Health Chronic Prostatitis Collaborative Research Network studies.

Chronic prostatitis/chronic pelvic pain syndrome remains an enigmatic medical condition. Creation of the National Institutes of Health-funded Chronic Prostatitis Collaborative Research Network (CPCRN) has stimulated a renewed interest in research on and clinical aspects of chronic prostatitis/chronic pelvic pain syndrome. Landmark publications of the CPCRN document a decade of progress. Insights from these CPCRN studies have improved our management of chronic prostatitis/chronic pelvic pain syndrome and offer hope for continued progress.

The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown. METHODS: We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia. RESULTS: The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone. CONCLUSIONS: Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.

Prevalence and risk factors for urinary incontinence in women with type 2 diabetes and impaired fasting glucose: findings from the National Health and Nutrition Examination Survey (NHANES) 2001-2002.

OBJECTIVE: Diabetes is associated with increased risk of urinary incontinence. It is unknown whether women with pre-diabetes, or impaired fasting glucose (IFG), have increased prevalence of incontinence. We determined the prevalence of, and risk factors for, incontinence among U.S. women with diabetes and IFG. RESEARCH DESIGN AND METHODS: The 2001-2002 National Health and Nutrition Examination Survey measured fasting plasma glucose and obtained information about diabetes and urinary incontinence among 1,461 nonpregnant adult women. Self-reported weekly or more frequent incontinence, both overall and by type (urge and stress), was our outcome. RESULTS: Of the 1,461 women, 17% had diabetes and 11% met criteria for IFG. Prevalence of weekly incontinence was similar among women in these two groups (35.4 and 33.4%, respectively) and significantly higher than among women with normal fasting glucose (16.8%); both urge and stress incontinence were increased. In addition to well-recognized risk factors including age, weight, and oral estrogen use, two microvascular complications caused by diabetes, specifically macroalbuminuria and peripheral neuropathic pain, were associated with incontinence. CONCLUSIONS: Physicians should be alert for incontinence, an often unrecognized and therefore undertreated disorder, among women with diabetes and IFG, in particular those with microvascular complications. The additional prospect of improvements in their incontinence may help motivate some high-risk women to undertake difficult lifestyle changes to reduce their more serious risk of diabetes and its sequelae.