Overactive Bladder and Outlet Obstruction in Men

Lower urinary tract symptoms (LUTS), overactive bladder, (OAB), and benign prostatic hyperplasia (BPH) are very commonly experienced in men. The mainstay of pharmacotherapy for OAB is the antimuscarinic class of drugs. There has been reluctance to prescribe these agents to men with BPH due to the risk of precipitating urinary retention. Several trials have supported the efficacy and safety of antimuscarinics in treating men with LUTS, alone, or in combination with α-blocker therapy. The combination of 5-α-reductase inhibitors with antimuscarinic agents or surgery are other effective treatments for men with BPH and OAB.     

Overactive bladder and men: Indications for anticholinergics

Similar to bladder outlet obstruction (BOO), overactive bladder (OAB) symptoms are very common and increase in prevalence as men age. Whether or not OAB symptoms are thought to be secondary to BOO, the goal of treatment of symptoms should result in an improved quality of life and ultimately prevent clinical deterioration. A common dilemma when treating men with obstruction and OAB is the risk of acute urinary retention or morbidities related to increasing postvoid residuals. In this article, the relationship of OAB to BOO is examined and the role of urodynamics and data on the use of anticholinergics in men with OAB and obstruction are reviewed. An algorithm for managing men with OAB also is proposed. In men with OAB without evidence of obstruction (including OAB after treatment for BOO), first-line medical therapy with anticholinergics is indicated. However, in men with OAB and concomitant BOO, nomogram has been developed to assist in the management of patients at risk for urinary retention. Men with significant obstruction should be appropriately treated to decrease bladder outlet resistance before adding anticholinergics for the treatment of OAB.     

Pathophysiology and treatment of the overactive bladder syndrome in an aged male patient with voiding difficulty: pharmacological treatment

Pharmacolgical treatment is the main stay in the treatment of overactive bladder (OAB). However, it can be difficult to treat the patients with OAB and voiding difficulty. The present patient was a 75-year-old male, who had wet OAB and voiding difficulty with slight enlargement of the prostate (ultrasound-estimated prostate volume; 28 ml) and a medical history of cerebral infarction. The analysis of clinical data gained from the patients with lower urinary tract symptoms in our institution suggested that the etiology of OAB in this patient was neurogenic bladder with high probability (nearly 80%), and the probability of the existence of bladder outlet obstruction (BOO) was approximately 40%. Given the high probability of the neurogenic OAB, the first-line therapy should be a pharmacological treatment. If he had BOO, the treatment should start with alpha-adrenoceptor blockers, and also the combination of anticholinergic drugs and alpha-blockers would be beneficial. If he had impaired detrusor contractility, we have no evidence-based proposal for his treatment.     

New Data on Tolterodine: Do Recent Findings Dispel Questions About Treating Overactive Bladder in Men?

Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence (UUI), usually with frequency and nocturia. These symptoms represent a subset of lower urinary tract symptoms (LUTS). Results from epidemiologic studies conducted in the United States and Europe suggest that OAB affects 11–16% of men. Although OAB is frequently associated with detrusor overactivity, the coexistence of OAB symptoms and prostatic conditions (e.g., benign prostatic hyperplasia, benign enlargement of the prostate, and bladder outlet obstruction [BOO]) in men adds complexity to the diagnosis and appropriate treatment. Men with OAB symptoms are more often prescribed pharmacotherapies that target the prostate (e.g., α-receptor antagonists, 5α-reductase inhibitors) rather than the bladder (e.g., antimuscarinics), possibly due to a tendency among clinicians to attribute all LUTS to prostate disease. Thus, a subset of men who receive treatment for prostatic conditions may have persistent OAB symptoms. Moreover, some physicians may be concerned that the inhibitory effect of antimuscarinic agents on detrusor contraction could aggravate the voiding difficulties of, or cause urinary retention in, men with OAB and possible BOO. Recent prospective studies and post hoc analyses of data from men with OAB symptoms and other LUTS, with or without concomitant BOO (not significant BOO at risk for urinary retention), have suggested that tolterodine improves OAB symptoms without an increased incidence of acute urinary retention. However, the literature would benefit from larger and longer placebo-controlled studies.     

The pathophysiology underlying overactive bladder syndrome possibly due to benign prostatic hyperplasia

The pathophysiology in the development of overactive bladder syndrome (OAB) possibly due to benign prostatic hyperplasia (BPH) has not fully been understood. The clinical study in male outpatients aged over 50 years with lower urinary tract symptoms showed that the frequency of urgency was significantly associated with aging, bladder outlet obstruction (BOO) and benign prostatic enlargement (BPE). From the results of the experiments we did using rats, the mechanisms underlying the development of OAB were suggested as follows. The functional impairment of acetylcholine neuron in the central nervous system is induced by aging and decreases the bladder capacity. Non-voiding contractions of the bladder may have some bearing on OAB associated with BOO. The C-fiber in the urethra may be involved in the generation of the detrusor overactivity associated with BPE. These results showed that the pathophysiology of OAB related to BPH is quite complex, suggesting that a multidisciplinary approach is necessary for the treatment.     

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.     

Transdermal drug delivery treatment for overactive bladder

Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and incontinence, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing side effects (e.g., dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin (N-DEO) is produced and this compound is deemed to be responsible for anticholinergic side effects such as dry mouth. This novel oxybutynin formulation offers patients with OAB and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.     

高选择性M受体阻滞剂治疗高龄BPH患者膀胱过度活动症的疗效及安全性

目的探讨高选择性M受体阻滞剂索利那新治疗高龄BPH患者膀胱过度活动症（OAB）的疗效及安全性。方法选取2010年7月至2011年5月于我院泌尿外科门诊就诊、年龄≥75岁、确诊为OAB的BPH患者30例,给予索利那新治疗,每日1次,每次5mg,治疗周期3个月。治疗前后以排尿日记、国际前列腺症状评分（IPSS）、膀胱过度活动症状评分（OABSS）、患者感知膀胱症状情况分级量表（PPBC）、生活质量评分（QOL）为主要疗效指标,对疗效及服药安全性进行评价。结果治疗后的24h平均尿急次数、24h平均排尿次数、夜尿次数及每周尿失禁次数均较治疗前好转;IPSS、OABSS、PPBC、QOL评分均低于治疗前,差异具有统计学意义（均P〈0.05）。9例患者出现轻度口干、便秘等不良反应,均能耐受,对症治疗后缓解。2例患者出现排尿困难情况,停药1周并加用α受体阻滞剂后缓解。结论高选择性M受体阻滞剂索利那新治疗高龄BPH患者的膀胱过度活动症疗效较好,不良反应轻,是一种相对安全有效的药物治疗方法。     

Comparison of doxazosin with or without tolterodine in men with symptomatic bladder outlet obstruction and an overactive bladder

OBJECTIVE: To assess the efficacy of combined treatment with doxazosin and tolterodine, as although alpha-blockers are commonly used and generally effective in men with symptomatic bladder outlet obstruction (BOO), a subset of men with BOO and overactive bladder (OAB) symptoms often complain of persistent symptoms. PATIENTS AND METHODS: In a prospective study of 144 consecutive men with BOO at one tertiary urology centre, all had a baseline pressure-flow urodynamic study and were then subdivided into those with BOO or BOO + OAB, based on absence or presence of involuntary detrusor contractions. The Abrams-Griffiths nomogram was used to determine obstructive BOO. After the initial evaluation, all patients were treated with doxazosin 4 mg/day for 3 months. In patients with no symptomatic improvement, tolterodine 2 mg twice daily was added for an additional 3 months. RESULTS: Of the 144 patients, 76 (53%) were diagnosed as having BOO and 68 (47%) BOO + OAB. The patients with BOO + OAB were older (P < 0.05) and had a higher International Prostate Symptom Score. After 3 months of treatment with doxazosin, 60 (79%) with BOO and 24 (35%) BOO + OAB reported a symptomatic improvement. In those patients with no improvement, six of 16 with BOO and 32 of 44 (73%) with BOO + OAB improved after adding tolterodine. Acute urinary retention developed in only two of 60 men (3.3%) treated with the combined therapy. CONCLUSION: About half of men with symptomatic BOO had an OAB; while about three-quarters of men with symptomatic BOO and no OAB improved with doxazosin, only a third with BOO + OAB were helped with doxazosin alone. Combining tolterodine with doxazosin was effective in three-quarters of men with BOO + OAB. Overall, most men with BOO with or with no OAB were helped with doxazosin alone or with the addition of tolterodine.     

Initial combined treatment with anticholinergics and α-blockers for men with lower urinary tract symptoms related to BPH and overactive bladder: a prospective, randomized, multi-center, double-blind, placebo-controlled study

We aimed to evaluate the efficacy and safety of combination treatment using anticholinergics with α-blocker for initial treatment of both overactive bladder (OAB) and other lower urinary tract symptoms (LUTS), secondary to BPH. A 12-week, randomized, double-blind, placebo-controlled trial was conducted at four urology clinics in Korea, involving men, aged 50 years or older, with LUTS related to BPH and OAB. A total of 176 patients were randomly assigned to receive doxazosin (4 mg) plus placebo or doxazosin (4 mg) plus tolterodine SR (4 mg), once a day for 12 weeks. Changes from baseline in total International Prostate Symptom Score (IPSS), bladder diary variables, patient perception of bladder condition (PPBC), uroflowmetry, postvoid residual volume and IPSS subscores (voiding and storage) were analyzed. Of the 176 enrolled patients, 91 had doxazosin gastrointestinal therapeutic system (GITS) and placebo, and 85 had combined medication with doxazosin GITS and tolterodine SR. Compared with the doxazosin plus placebo group, the doxazosin plus tolterodine group showed significant reductions in IPSS storage subscore and improvement in the quality of life item, urgency episodes, as well as in micturition frequency at weeks 4 and 12. However, it failed to improve PPBC at week 4 as well as at week 12. Earlier intervention with anticholinergics plus α-blocker was tolerated well, including the questions about urinary retention (n=1) and dry mouth (n=2). Initial combination treatment of anticholinergics plus α-blocker showed positive results for men with LUTS related to BPH and OAB symptoms and did not increase the risk of urinary retention.     

When to Treat the Prostate,the Bladder,or Both?

ContextPharmacological therapy for relieving lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) has evolved during the past years. The possible benefits of combination therapies to prevent disease progression or to treat LUTS/BPH with concomitant overactive bladder (OAB) or erectile dysfunction (ED) are currently studied.ObjectivesTo review the evidence provided in clinical trials and to assess the current medical practice concerning the pharmacological treatment of men suffering from LUTS/BPH.Evidence acquisitionThis paper is based on a presentation during the symposium “The future of LUTS/BPH: management beyond the prostate” at the European Association of Urology's 2008 annual meeting. The results of a Web survey evaluating the opinion of urologists about treatment of LUTS/BPH patients were discussed and an update lecture on medical therapy for LUTS/BPH was given.Evidence synthesisMen who are highly bothered by their symptoms but with a low risk of disease progression can achieve fast relief of symptoms with α₁-adrenoceptor (α₁-AR) antagonist monotherapy. Those patients at risk for LUTS/BPH progression can benefit from additional 5α-reductase inhibitor therapy. Concomitant OAB symptoms in LUTS/BPH patients can be treated with a combination of an α₁-AR antagonist and an antimuscarinic agent. An α₁-AR antagonist combined with a phosphodiesterase-5 inhibitor might improve symptoms in men with lower urinary tract symptoms (LUTS) and concomitant ED.ConclusionsThe pharmacological treatment of LUTS/BPH patients should be adapted to their individual risk of progression and their individual symptom profile.     

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.     

Transdermal oxybutynin for overactive bladder

Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and frequency and in decreasing incontinence episodes, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing the side effects (eg, dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin is produced (this compound is deemed responsible for the anticholinergic side effects such as dry mouth). This novel oxybutynin formulation offers patients who have overactive bladder and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.     

经尿道前列腺电切术后下尿路症状改善的原因分析

目的分析存在下尿路症状（lower urinary tract symptoms,LUTS）的男性患者接受经尿道前列腺电切（transurethral resection of prostate,TURP）术后症状改善的原因。方法对2006年3月至2010年2月于北京朝阳区院接受TURP手术后症状改善的65例患者进行回顾性分析。记录术前国际前列腺症状评分（international prostate symptom score,IPSS）和生活质量（quality of life,QOL）评分,尿流率,残余尿及压力一流率检查的各项数据,术后随访并再次记录上述指标。按术前存在膀胱过度活动症（overactive bladder,OAB）及膀胱出口梗阻（bladder outlet obstruction,BOO）与否,分别将患者分为OAB组（n=34）与非OAB亚组（n=31）,及B00（n=48）与非B00亚组（n=17）。结果65例患者TURP术中无明显并发症发生,术后5例患者前尿道狭窄,19例逆向射精,11例急迫性尿失禁加重,分别给予针对性处理后症状缓解。整体患者术前、术后相应数据的配对t检验结果显示：术前IPSS评分22．67±4．92,术后IPSS10．51±5．79;术前刺激评分10．27土3．53,术后刺激评分6．32±3．45;术前梗阻评分12．13±3．92,术后梗阻评分4．19±3．33;术前QOL评分4．57±0．89,术后QOL评分2．27±1．30;术前尿流率（5．78±2．91）mL／s,术后尿流率（12．39±5．17）mL／s,术前残余尿（98．98±16．27）mL和术后残余尿（34．43±18．61）mL的配对t检验结果均有显著性意义（P〈0．01）,进一步分析两个亚组的相应数据具有统计学意义。站论前列腺增生导致下尿路症状的男性患者经尿道前列腺电切手术前后IPSS评分（刺激评分及梗阻评分）,生活质量评分均有显著变化;术前存在B00（伴或不伴OAB）的患者可于TURP术后症状改善、无或可疑BOO的患者也可试行TURP手术,术后症状也有望改善。     

Performance of urinary biomarkers in differentiating dysfunctional voiding in women with overactive bladder syndrome: a prospective pilot study

International Urology and Nephrology - Dysfunctional voiding (DV) in women is a common disorder that causes bladder outlet obstruction (BOO) and may aggravate overactive bladder (OAB) symptoms. The...     

Inhibitory effects of nicorandil, a K ATP channel opener and a nitric oxide donor, on overactive bladder in animal models

OBJECTIVES

To investigate the effects of nicorandil, an ATP‐sensitive potassium (K_ATP) channel opener with a nitric oxide (NO) donor property, on overactive bladder (OAB) in animal models. Nicorandil is currently used clinically to treat ischaemic heart disease.

MATERIALS AND METHODS

Three animal OAB models were used: (i) C‐fibre mediated bladder overactivity by infusion of a low concentration of acetic acid (AA) into the bladder in female Wistar rats; (ii) bladder outlet obstruction (BOO) created by partial urethral obstruction in female Wistar rats; and (iii) neuronal NO synthase (nNOS) knockout (KO) mice with urinary frequency. The effects of nicorandil and KRN2391, both of which act as K_ATP channel openers and NO donors, on the OAB models were examined.

RESULTS

Cystometry showed that intravesical instillation of nicorandil and KRN2391 successfully inhibited OAB induced by intravesical instillation of AA. In the BOO model compared with untreated BOO rats, both nicorandil (1 and 3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency. Compared with wild‐type mice, nNOS KO mice had urinary frequency with no change in the total urine volume. Nicorandil (3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency in nNOS KO mice.

CONCLUSIONS

Our in vivo results show that nicorandil, a K_ATP channel opener with a NO donor property, can suppress OAB from both neurogenic and myogenic causes. Nicorandil appears to be a promising candidate for clinical use in patients with OAB.     

Die überaktive Blase im Kindesalter

Enuresis is one of the most frequent urinary symptoms in children. 80% suffer from primary enuresis nocturna. 20% have urinary incontinence with additional symptoms of frequency, urgency and daytime incontinence, which is also defined in children as overactive bladder in absence of urinary tract infections, neurological, anatomical or further local pathology (OAB in childhood). The underlying pathophysiology is a maturation arrest of the bladder control resulting in detrusor hyperactivity. In most of the cases the differentiation between enuresis and OAB is easily possible with non-invasive primary diagnostic procedures.Invasive diagnostic tools like video urodynamic studies may become necessary when first-line therapy fails. The treatment options comprise bladder training with timed voiding and drink protocols (urotherapy) as well as pharmacologic relaxation of detrusor instability by anticholinergic drugs.     

Management of OAB in Those Over Age 65

The International Continence Society (ICS) defines overactive bladder (OAB) as an association of symptoms including “urgency, with or without urge incontinence, usually with increased frequency and nocturia”. This conditon has been associated with a decrease in quality of life and a higher related risk of overall health condition decrease, and is rising since its prevalence increases with age and the forecast for the world population estimates an increase of those over 65 years old. Aging alone can be considered a major risk factor for developing OAB symptoms that are considered multifactorial and due to body tissue and anatomic changes, lifestyle-associated factors, comorbidities and personal characteristics. The high prevalence of this condition and multiple etiology factors makes of its treatment a challenge—especially in the older population. A major concern over OAB treatment of elderly patients is the risk of cognitive side effects due to the pharmacologic treatment with anticholinergic drugs. First-line treatment for OAB symptoms are the use of pharmacologic therapy with antimuscarinic drugs, which has been proved to be effective in controlling urgency, urge incontinence episodes, incontinence episodes, and nocturia. The impact caused by this condition is significant regarding the economic and human costs associated bringing into attention the need of studying and reviewing this specific population. Conservative Management and Lifestyle Modifications: Behavioral therapy’s aims are to reduce urinary frequency and urgency to an accepted level and to increase bladder outlet volume. It consists of actions to teach patients to improve and learn bladder control. Lifestyle modifications are a conjunct of daily activities that can be managed to have the lowest interference on the functioning of the urinary tract. Pharmacologic Therapy: There are various medications with antimuscarinic properties available for the treatment of OAB symptoms. The most commonly used are oxybutinin, tolterodine, solifenacin, darifenacin, fesosterodine and trospium. Second-line Therapy: OAB treatment accounts for some refractory to conventional treatment patients who will require alternative therapies to achieve improvement of symptoms as the use of intradetrusor injection of botulinum A toxin by binding to receptors on the membrane of cholinergic nerves causing temporary chemodenervation and consequent muscle relaxation. Neuromodulation is also an effective therapy that aims to achieve inhibition of detrusor activity by continuous neural stimulation through peripheral nerves as the use of the tibial nerve or central as it is performed by direct spine stimulation on sacral roots through the implantation of an automated generator. In conclusion, evidence from the literature has shown that antimuscarinic treatment of OAB in the elderly population is safe and effective in improving symptoms and patient’s quality of life. Managing OAB symptoms in this population is a great challenge. An optimal therapeutic approach to treat should involve medical treatment with drug and behavioral therapy in addition to lifestyle advice.     

The detrusor muscle: an innocent victim of bladder outlet obstruction

OBJECTIVES: Benign prostatic hyperplasia (BPH) is considered a frequent cause of bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS), although the physiopathologic mechanism through which BPH causes LUTS is not clear. Several morphologic and functional modifications of the bladder detrusor have been described in patients with BPH and could play a direct role in determining symptoms. The opinion is spreading that the enlarged prostates in patients with LUTS is nothing more than a mere bystander. Evidence has accumulated, however, supporting the role of BPH-related BOO as the direct cause determining bladder dysfunction and indirectly causing urinary symptoms. The present review addresses the bladder response to BOO, particularly focusing on the physiopathologic cascade that links obstructive BPH to bladder dysfunction. METHODS: A literature review of peer-reviewed articles has been performed, including both in vivo and in vitro studies on human tissue and animal model experiments. RESULTS: Epithelial and smooth muscle cells in the bladder wall are mechanosensitive, and in response to mechanical stretch stress caused by BOO, undergo modifications of gene expression and protein synthesis. This process involves several transduction mechanisms and finally alter the ultrastructure and physiology of cell membranes, cytoskeleton, contractile proteins, mitochondria, extracellular matrix, and neuronal networks. CONCLUSIONS: BOO is the initiator of a physiopathologic cascade leading to deep changing of bladder structure and function. Before being a direct cause of storing-phase urinary symptoms, the bladder is the first innocent victim of prostatic obstruction.