Urinary nerve growth factor in women with overactive bladder syndrome

Study Type – Aetiology (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Urinary nerve growth factor levels were higher in women with OAB‐dry and OAB‐wet compared to the controls. The link between female OAB and risk factors such as obesity and menopause has not been determined yet. This study found ageing, menopause, or higher BMI did not influence the urinary NGF levels in OAB women. Higher urinary NGF levels in OAB women could be an inflammatory disorder unrelated to ageing or obesity.

OBJECTIVE

? To measure urinary nerve growth factor (NGF) in women with overactive bladder (OAB)‐dry and OAB‐wet and investigate the association of urinary NGF expression with these factors.

PATIENTS AND METHODS

? Differentiation between OAB‐wet and OAB‐dry was based on symptoms and a 3‐day voiding diary. ? Urinary NGF levels were measured by enzyme‐linked immunosorbent assay (ELISA). ? The urinary NGF levels were compared among controls, OAB‐dry and OAB‐wet subgroups, and also between OAB patients ≥55 years and <55 years, as well as between patients with a body mass index (BMI, kg/m²) <20, 20–30 and >30.

RESULTS

? A total of 113 women with OAB‐dry, 106 with OAB‐wet and 84 controls were enrolled. The urinary NGF/creatinine (Cr) levels were significantly highest in OAB‐wet (2.13 ± 3.87) and second highest in OAB‐dry (0.265 ± 0.59) compared to controls (0.07 ± 0.21). ? Analysis of urinary NGF or NGF/Cr levels among controls, OAB‐dry and OAB‐wet groups by age and BMI showed no significant differences, except for the OAB‐dry group. ? Urinary NGF/Cr was not significantly correlated with age (P= 0.088) or BMI (P= 0.886) in women with OAB‐dry and OAB‐wet.

CONCLUSIONS

? Urinary NGF levels were significantly higher in women with OAB‐dry and even higher in women with OAB‐wet. ? The urinary NGF level was not associated with ageing, menopause or higher BMI either in controls or OAB patients.     

索利那新治疗膀胱过度活动症对逼尿肌功能的影响

目的 评估索利那新治疗膀胱过度活动症(overactive bladder,OAB)患者12周前后逼尿肌功能的变化.方法 2010年3-7月,20例OAB患者服用索利那新治疗.男12例,女8例.年龄21～83岁,平均43岁.病程1～20年,平均8年.患者连续服用索利那新5 mg/d 12周.服药前后行尿动力学检查,观察逼尿肌功能变化、记录OABSS得分、感知膀胱症状量表(PPBC)评分,统计学比较治疗前后的差异.结果 患者治疗前后平均逼尿肌无抑制收缩波个数分别为2.3±2.4与0.6±1.3,差异有统计学意义(P＜0.05);其中6例患者服药后逼尿肌无抑制收缩完全消失.治疗前后膀胱初次排尿感容量(103±67 ml与178±89 ml)、膀胱容量(189±133 ml与299±89 ml)差异有统计学意义(P＜0.01);膀胱顺应性、最大尿流率时逼尿肌压力差异无统计学意义(P＞0.05).服药前后OABSS量表的尿急评分(5.0±0.0与2.8±2.0)、白天排尿评分(1.3±0.5与0.4±0.7)、夜尿评分(2.9±0.4与1.4±0.92)、尿失禁评分(3.3±2.1与1.6±2.1)、PPBC评分(5.5±0.5与2.9±1.6)差异均有统计学意义(P＜0.05).6例患者诉有口干现象.结论 索利那新12周治疗可明显降低OAB患者逼尿肌无抑制收缩,增加逼尿肌储尿量,减少OAB症状,提高生活质量.

Abstract：

Objective To investigate the effects of solifenacin on the detrusor instability of patients with overactive bladder (OAB).Methods A total of 20 outpatients with OAB of.1 - 20 ( mean, 8 )years, 12 males and 8 females, aged 21 - 83 ( mean, 43) years were included in this study.Five mg solifenacin was given orally once daily for 12 weeks.Before and after treatment, overactive bladder symptom score (OABSS), patient perception of bladder condition symptoms rating scale (PPBC), and filling cystometry was performed.Results Before and after solifenacin administration, significant decrease were detected in term of unstable detrusor waves ( 2.3 ± 2.4) vs (0.6 ± 1.3 ) ( P ＜ 0.05 ), and detrusor overactivity ( DO ) disappeared in 6 patients.Bladder capacities at first desire to void and maximum bladder capacity were significantly increased (P ＜0.01 ).Bladder compliance and detrusor pressure at maximum urine flow had no significant difference (P ＞ 0.05 ).All patients had significant improvement in OAB symptoms evaluating by OABSS and PPBC ( P ＜ 0.05 ).Six patients had mild side effect of dry mouth and could be relieved by drinking more water.Conclusion Urodynamically, solifenacin decreases the detrusor overactivity, increases the bladder capacity and improves the quality of life of OAB patients.     

Changes of urinary nerve growth factor and prostaglandins in male patients with overactive bladder symptom

AIM: Nerve growth factor (NGF) and prostaglandins (PG) in the urinary bladder can be affected by pathology of bladder, and this change can be noted in the urine. This study was performed to investigate the changes in urinary NGF and PG in male patient with overactive bladder (OAB) symptoms. METHODS: The study group included 75 male patients with OAB symptoms and 20 males without bladder symptoms as controls. Evaluation included history-taking, urinalysis, International Prostate Symptom Score (IPSS) and urodynamic study. The NGF, PGE2, PGF(2alpha) and PGI2 levels in voided urine were analyzed by enzyme linked immunosorbent assay and these results were compared in control and OAB patients. Also, the urinary levels of NGF and PG were correlated with IPSS score and urodynamic parameters in OAB patients. RESULTS: The urinary levels of NGF and PGE2 were signi fi cantly increased in patients with OAB compared with control (P < 0.05). The urodynamic study in OAB patients showed that more than half of the patients had detrusor overactivity and bladder outlet obstruction. The incidence of detrusor underactivity was noted in seven patients in the OAB group. The urinary level of PGE2 was decreased in patients with detrusor underactivity compared with patients without detrusor underactivity (P < 0.05), and negatively correlated with maximum bladder capacity in OAB patients (P < 0.05). CONCLUSIONS: NGF and PG may have important role in male patients with OAB, and the urinary level of PGE2 can change according to detrusor function. Therefore, these results may be used as urinary markers to evaluate the OAB symptoms.     

索利那新加坦索罗辛治疗膀胱过度活动症的疗效分析

目的 探讨索利那新加坦索罗辛治疗膀胱过度活动症(OAB)的疗效.方法 OAB患者53例,男15例,女38例.年龄29～72岁,平均43岁.随机分为2组,A组为单用索利那新组(27例),B组为索利那新加用坦索罗辛组(26例).服药方法:索利那新5 mg/d,坦索罗辛0.2 mg/d.连续14 d后随访,再进行OABSS评分.结果 A组患者治疗前后尿急评分分别为(3.3±1.0)与(1.9±0.6)分,OABSS评分分别为(10.8±4.9)与(5.2±1.8)分;B组患者治疗前后尿急评分分别为(3.6±1.0)与(0.9±0.1)分,OABSS评分分别为(10.7±1.9)与(3.9±1.8)分,2组治疗前后差异均有统计学意义(P＜0.05),2组治疗后尿急评分和OABSS评分差异有统计学意义(P＜0.05).结论 索利那新加用坦索罗辛可以有效缓解OAB患者的尿急症状并降低OABSS评分,索利那新加用坦索罗辛疗效好于单用索利那新.

Abstract：

Objective To evaluate the efficacy of solifenacin with or without tamsulosin in patients with overactive bladder (OAB).Methods Fifty-three patients with OAB were randomly divided into two groups (group A 27 patients, group B 26 patients).The patients received either solifenacin 5 mg/day in group A or combined with Tamsulosin 0.2 mg/day in group B for two weeks.During the treatent period all the patients recorded voiding and adverse events in a diary.The symptoms of urgency, frequency, incontinence were evaluated by OABSS scores at the begining and end of the therapy period.The results of the efficacy and safety were analyzed by using SPSS 13.0.Results The OABSS scores at the begining and end for the two groups were significantly different ( P ＜ 0.01 ).In both groups the efficacy was obvious.The OABSS scores at the end of the therapy between group A and B were significantly different (P ＜0.05 ).The efficacy of group B was better than that of group A.Conclusion The efficacy of solifenacin combined with tamsulosin was better than solifenacin alone in OAB.     

Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder

OBJECTIVE

To determine urinary nerve growth factor (NGF) levels in patients with overactive bladder (OAB) and after treatment with antimuscarinics.

PATIENTS AND METHODS

Urinary NGF levels were measured in 38 ‘normal’ controls and 70 patients with OAB. Patients were treated with tolterodine 4 mg once daily. Urinary NGF levels were measured by enzyme‐linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cr). The urinary NGF/Cr levels and urgency severity scale (USS) were compared at baseline, 1, 2 and 3 months after antimuscarinics, and 1 month after discontinuing treatment.

RESULTS

The urinary NGF/Cr level was very low in normal controls with a mean (sem ) of 0.005 (0.003). Patients with OAB had significantly higher baseline urinary NGF/Cr levels than the controls. Urinary NGF/Cr levels were significantly reduced at 3 months in 50 responders (1.10 [0.26] before vs 0.41 [0.09] after, P = 0.008) but not in the 20 non‐responders (1.38 [0.54] before vs 1.30 [0.46] after, P = 0.879). However, after discontinuing antimuscarinic treatment for 1 month, the urinary NGF/Cr level was elevated in 23 responders at 0.83 (0.33) and in five non‐responders at 2.72 (1.41). The USS scores significantly changed with the change of urinary NGF/Cr levels in responders at different time points. The voided volume increased but maximum urinary flow rate and postvoid residual volume did not increase in responders after 3‐months of antimuscarinic treatment. The limitation of this study was the lack of a control arm for comparison.

CONCLUSIONS

Changes in the urinary NGF levels were associated with the changes of the USS scores after antimuscarinic treatment and discontinued medication. The urinary NGF level could be a potential biomarker for evaluating therapeutic results of antimuscarinics therapy.     

Urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder

Objectives: To investigate the urodynamic effects of solifenacin in untreated female patients with symptomatic overactive bladder (OAB). Methods: A total of 52 untreated female patients with OAB symptoms were given 5 mg solifenacin once daily for 12 weeks. Before and after treatment, the frequency volume chart, overactive bladder symptom score (OABSS), postvoid residual volume, filling cystometry and adverse events were evaluated. Results: After solifenacin treatment, OAB symptoms were improved, voided volume was increased and voiding number was decreased. Bladder capacities at the first sensation of bladder filling, first desire to void and strong desire to void were significantly increased. Intravesical pressure at the first sensation of bladder filling was significantly decreased. Detrusor overactivity (DO) disappeared in five patients. For 28 patients with persisting DO after treatment, bladder capacity at DO was significantly increased. Both groups with and without DO at baseline had significant improvements of OAB symptoms. Conclusions: Solifenacin urodynamically increases bladder capacity in female patients with symptomatic OAB.     

Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder

AIMS: The origin of overactive bladder (OAB), which is a leading cause of lower urinary tract symptoms, remains unknown. Nerve growth factor (NGF) is one of the neurotrophic factors which are needed for the maintenance of sensory neurons. It is known that too much expression of NGF may induce bladder hyperactivity. In this study, we explored the correlation of the level of urinary NGF with various pathogenic OAB such as idiopathic, neurogenic OAB, and bladder outlet obstruction (BOO). METHODS: The study group included 51 OAB patients. Thirteen patients (7 females and 6 males) had idiopathic detrusor overactivity (DO) without BOO, 6 female idiopathic OAB without DO (sensory urgency), 16 patients with BOO due to BPH, and 16 patients with neurogenic DO (10 due to spinal cord injury (SCI), 6 due to cerebrovascular disease (CVD)). Thirty-two patients who had normal cystometric findings (23 females and 9 males) without OAB symptoms were used as controls. Urinary NGF levels were measured by enzyme-linked immunosorbent assay technique (ELISA) and the results were normalized based on creatinine (Cr) concentration. RESULTS: The urinary NGF levels in patients with neurogenic DO due to SCI, BOO, and sensory urgency were significantly higher compared with those of normal cystometric finding patients. However, the levels of urinary NGF were not statistically significant between patients with idiopathic DO without BOO, neurogenic DO due to CVD and patients with normal cystometric findings. CONCLUSIONS: These data suggest that urinary NGF levels could serve as a basis for adjunct diagnosis of OAB.     

Nocturnal polyuria and nocturia relief in patients treated with solifenacin for overactive bladder symptoms

The objectives of this study are to determine whether patients with overactive bladder (OAB) and nocturia achieved relief of their nighttime voiding symptoms when treated with solifenacin and whether having nocturnal polyuria (NP) affected that response. The patients pooled from four phase III clinical trials were evaluated for reductions in nocturia episodes after treatment with solifenacin (5 or 10 mg) or placebo. A second analysis was performed in patients with and without NP. The patients treated with solifenacin experienced statistically significant reductions in nocturia episodes; median reductions were −35.5% for 5 mg of solifenacin and −36.4% for 10 mg of solifenacin compared with −25.0% for placebo, and significantly more patients treated with solifenacin vs placebo achieved a mean nocturic frequency of ≤1 episode/night. Solifenacin significantly reduced nocturia episodes only in patients without NP (mean change was −0.61 episodes/night for both doses compared with −0.43 episodes for placebo). Solifenacin significantly improved nocturia symptoms only in OAB patients without NP.     

Long-term open-label solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome

OBJECTIVE: To examine safety and tolerability findings as primary endpoints, and efficacy outcomes as secondary endpoints, of solifenacin treatment over a period of up to 1 year. Long-term efficacy in the treatment of overactive bladder (OAB) syndrome depends in part on the patient's persistence with pharmacologic therapy. Agents with a favourable therapeutic index supporting high levels of patient satisfaction and persistence are needed. METHODS: The present study was a 40-week open-label extension of two 12-week, placebo-controlled, double-blind studies of solifenacin treatment in patients with OAB. Patients who completed the 12-week studies were offered participation in the open-label extension study. All patients who entered the open-label extension study initially received solifenacin 5 mg daily for 4 weeks, after which a flexible dosing regimen allowed patients to individualise their treatment (5 mg or 10 mg) at each of the 3 study visits. Safety and tolerability assessments (the primary variable) included adverse event reporting. Efficacy data were collected from micturition diaries completed at weeks 16, 28, 40, and 52. RESULTS: Ninety-one percent (1637/1802) of patients who completed the two 12-week randomised studies chose to participate in the long-term open-label extension study. A total of 81% of patients completed 40 weeks of open-label treatment. Solifenacin treatment was safe and well tolerated, and rates of anticholinergic side effects were relatively low. Only 4.7% of patients discontinued treatment owing to adverse events. Improvements in major symptoms of OAB were noted for all patients for up to 52 weeks of treatment. In patients randomised to solifenacin in the double-blind studies, there were small incremental improvements in all efficacy parameters (reductions in episodes per 24 hours of urgency, reductions in frequency and urge incontinence, and increases in volume voided per micturition) over the course of the extension study. Efficacy was confirmed when outcomes were assessed as a function of total solifenacin exposure. Patient satisfaction with solifenacin tolerability (85%) and efficacy (74%) were high. These results indicate that long-term treatment with solifenacin was well tolerated and associated with improvements in efficacy parameters based on patient diary data recorded over the 12-month treatment period. Moreover, the high level of patient satisfaction reported appeared to correlate well with the quantified improvements in key symptoms demonstrated in this study. CONCLUSIONS: Long-term therapy with solifenacin resulted in a favourable tolerability profile, and was associated with improvements in efficacy parameters based on diary data recorded over a 12-month period. This balance of tolerability and efficacy with solifenacin was associated with excellent persistence with therapy. These results suggest that solifenacin may be useful for the long-term treatment of the chronic symptoms associated with OAB.     

Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder

PURPOSE: NGF and PGs in the bladder can be affected by pathological changes in the bladder and these changes can be detected in urine. We investigated changes in urinary NGF and PGs in women with OAB. MATERIALS AND METHODS: The study groups included 65 women with OAB and 20 without bladder symptoms who served as controls. Evaluation included patient history, urinalysis, a voiding diary and urodynamic studies. Urine samples were collected. NGF, PGE2, PGF2alpha and PGI2 were measured using enzyme-linked immunosorbent assay and compared between the groups. In addition, correlations between urinary NGF and PG, and urodynamic parameters in patients with OAB were examined. RESULTS: Urinary NGF, PGE2 and PGF2alpha were significantly increased in patients with OAB compared with controls (p <0.05). However, urinary PGI2 was not different between controls and patients with OAB. In patients with OAB urinary PGE2 positively correlated with volume at first desire to void and maximum cystometric capacity (p <0.05). Urinary NGF, PGF2alpha and PGI2 did not correlate with urodynamic parameters in patients with OAB. CONCLUSIONS: NGF and PGs have important roles in the development of OAB symptoms in female patients. Urinary levels of these factors may be used as markers to evaluate OAB symptoms.     

Changes in urinary nerve growth factor and prostaglandin E2 in women with overactive bladder after anticholinergics

Introduction and hypothesis

The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E₂ (PGE₂) in women with overactive bladder (OAB) following anticholinergic treatment.

Methods

A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE₂ levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared.

Results

Urinary NGF and PGE₂ levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE₂ levels were not significantly different between pre- and post-treatment in either group.

Conclusions

NGF and PGE₂ have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.