Benign prostatic hyperplasia

Male lower urinary tract symptoms (LUTS) have a multifactorial aetiology and are not simply solely due to bladder outflow obstruction (BOO) from benign prostatic hyperplasia (BPH). Other causes of LUTS include bladder dysfunction, malignant prostatic disease, urethral disease and medical conditions such as polyuria. Complications from BPH include acute urinary retention, urinary tract infection and haematuria. Following investigation, men are treated with medical therapy for BPH using α-blockers and 5α-reductase inhibitors. Some men undergo surgery for their symptoms and this can be in the form of open prostatectomy, transurethral resection of the prostate (TURP) and a variety of laser ablating and enucleating techniques.     

良性前列腺增生合并梗阻的相关因素

前列腺增生、膀胱出口梗阻和下尿路症状是一组既独立又相关的因素 ,良性前列腺梗阻 (BPO)则反映上述 3因素的交错和重合 ,也是临床治疗的直接目标 ,本文综述近年来有关前列腺增生合并BPO的相关因素的研究进展 ,着重讨论了尿流动力学、前列腺组织学、前列腺及其尿道形态学等改变与BPO关系     

Mirabegron for Male Lower Urinary Tract Symptoms

Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with BPH often present with a combination of obstructive and overactive bladder (OAB) symptoms. It is postulated that bladder outlet obstruction (BOO) from BPH results in concomitant OAB symptoms through ischemic induced variations in the response to neurotransmitters of both the detrusor and the urothelium. This altered response leads to the pathologic activation of the micturition reflex, generating sensory dysfunction and involuntary bladder contractions. Alpha-1 adrenoceptor antagonists (alpha-blockers) and 5-alpha reductase inhibitors (5-ARIs) are commonly used to treat the BOO caused by BPH. Anticholinergic agents are frequently used to treat concurrently OAB symptoms caused by the BOO. Unfortunately, anticholinergic medications demonstrate bothersome side effects and a theoretical risk of urinary retention. Basic science and clinical research has led to the development of a new class of pharmaceuticals for the treatment of overactive bladder with diminished risk of urinary retention and lacking many anticholinergic side effects. This novel compound, mirabegron (Mybertriq, Astellas Pharma US, Inc.), is a β₃-adrenoceptor agonist and represents a promising new class of oral agents designed for the treatment of OAB symptoms, with minimal effect on voiding.     

Pre-clinical evidence for the use of phosphodiesterase-5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms

OBJECTIVE: To evaluate the potential of sildenafil, vardenafil and tadalafil, all phosphodiesterase-5 (PDE-5) inhibitors used for treating erectile dysfunction, for treating benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: The mRNA expression of the PDE-5 was determined in rat LUT tissues. The PDE-5 inhibitors were also tested in organ-bath experiments and in a partial bladder outlet obstruction (BOO) rat model in vivo. RESULTS: The highest PDE-5 mRNA expression was in the bladder, followed by the urethra and prostate. PDE-5 inhibitors dose-dependently reduced the contraction of the isolated bladder, urethral and prostate strips. The rank order of potency was vardenafil > sildenafil > tadalafil. In human prostate stromal cells vardenafil inhibited cell proliferation and was more effective than tadalafil and sildenafil. In the BOO model, there was a reduction in the non-voiding contractions after bolus intravenous administration of 3 mg/kg sildenafil and vardenafil. CONCLUSION: These results show that PDE-5 is expressed in LUT tissues. PDE-5 inhibitors induced significant relaxation of these tissues, inhibited the proliferation of human prostate stromal cells and reduced the irritative symptoms of BPH/LUTS in vivo. Therefore, PDE-5 inhibitors could be used as an effective treatment for BPH/LUTS.     

α1-Adrenoceptor subtypes and lower urinary tract symptoms

Abstract:   Benign prostatic hyperplasia (BPH) is a common cause of urinary outflow obstruction in aging men leading to lower urinary tract symptoms (LUTS). α₁-Adrenoceptors (α₁ARs) antagonists (blockers) have become a mainstay of LUTS treatment because they relax prostate smooth muscle and decrease urethral resistance, as well as relieving bladder LUTS symptoms. A review of key recent clinical trials suggests new insights into the role of specific α₁AR subtypes in the treatment of LUTS.     

Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology

There is ample evidence from many epidemiological studies that lower urinary tract symptoms (LUTS) and sexual dysfunction are strongly linked, independently of age and comorbidities such as hypertension, diabetes, dyslipidaemia and coronary heart disease. However, a causal link between both conditions is not yet established. Four pathophysiological mechanisms currently support the relationship between LUTS and erectile dysfunction (ED): (i) The nitric oxide synthase (NOS)/NO theory; there is a reduction in NOS-containing nerves in the prostate and bladder/urethra in patients with bladder outlet obstruction (BOO), and that lack of NO or loss of protein kinase G causes ED; (ii) The autonomic hyperactivity and metabolic syndrome hypothesis: benign prostatic hyperplasia (BPH) may be part of the metabolic syndrome, which includes cardiovascular diseases (e.g. hypertension, ischaemic heart disease) and diabetes mellitus, known risk factors for ED. Hypertension, obesity, and hyperinsulinaemia have all been claimed to be associated with an increased sympathetic activity. Increased sympathetic activity is involved in LUTS/BPH and may have a role in ED/sexual dysfunction, with noradrenaline and alpha1-adrenoceptors representing a common link; (iii) the Rho-kinase activation/endothelin pathway; there can be increased Rho-kinase activity, and consequently calcium sensitivity of the contractile machinery, in prostate smooth muscle in BPH, the detrusor in BOO, corpora cavernosa in ED, and in the resistance vessels in hypertension. The actions of several factors beside noradrenaline (e.g. endothelin-1, angiotensin II), possibly involved in the increased smooth muscle activity found in both LUTS/BPH and sexual dysfunction, are dependent on Rho-kinase activity. Thus increased Rho-kinase activity might represent a common link between LUTS and sexual dysfunction; (iv) Pelvic atherosclerosis; animal models mimicking pelvic ischaemia and hypercholesterolaemia show similar smooth muscle alterations of the detrusor and corpora. Pelvic ischaemia may induce the biological modifications described above and may thus represent as well a common link between LUTS and sexual dysfunction. Studies treating one condition (e.g. ED) and measuring the impact on the other (e.g. LUTS) should further contribute to support this common link.     

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.     

Is the short‐term outcome of transurethral resection of the prostate affected by preoperative degree of bladder outlet obstruction,status of detrusor contractility or detrusor overactivity?

AIM: The aim of this study was to investigate whether the preoperative degree of bladder outlet obstruction (BOO), detrusor underactivity (DUA) or detrusor overactivity (DO) affected the short-term outcome of transurethral resection of the prostate (TURP) for patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). METHODS: Ninety-two patients with LUTS/BPH aged 50 years or older who were considered to be appropriate candidates for TURP were included in this study. Pressure-flow study and filling cystometry were performed to determine BOO, DUA and DO before TURP. The efficacy of TURP was determined at 3 months after surgery using the efficacy criteria for treatment of BPH assessed by the International Prostate Symptom Score, QOL index, maximum flow rate and postvoid residual urine volume. RESULTS: On preoperative urodynamics, 60%, 40% and 48% of patients showed BOO, DUA and DO, respectively. After TURP, 76% showed 'excellent' or 'good' overall efficacy, whereas only 13% fell into the 'poor/worse' category. The efficacy was higher as the preoperative degree of BOO worsened. In contrast, neither DO nor DUA influenced the outcome of TURP. However, the surgery likely provided unfavorable efficacy for patients having DO but not BOO. Only 20% of the patients who had both DO and DUA but did not have BOO achieved efficacy. CONCLUSIONS: Transurethral resection of the prostate is an effective surgical procedure for treatment of LUTS/BPH, especially for patients with BOO. DUA may not be a contraindication for TURP. The surgical indication should be circumspect for patients who do not have BOO but have DO.     

Connexin45 expression in the human obstructed detrusor muscle

Purpose  Patients with benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) frequently develop lower urinary tract symptoms (LUTS). To elucidate the underlying pathomechanisms we focused on altered cellular communication between detrusor cells. Methods  Bladder biopsies were collected from eight BPH patients with compensated BOO and from eight non-obstructed patients. Detrusor areas were separated by laser capture microdissection microscopy, and extracted RNA was subjected to quantitative RT-PCR for connexin43 and connexin45. Furthermore, localization of connexin45 and lysosome membrane associated protein 1 was studied by immunohistochemistry. Results  We found the human detrusor to express connexin45 rather than connexin43. Compared to controls, connexin45 expression was not significantly changed in detrusors of obstructed patients. However, connexin45 protein patterns were focally altered in obstruction. Conclusions  Our study is the first to provide evidence that connexin45-coupling of detrusor cells may be regionally impaired in patients with BOO due to BPH. The altered connexin45 coupling may contribute to LUTS.     

Clinical relevance of transurethral resection of the prostate in "asymptomatic" patients with an elevated prostate-specific antigen level

OBJECTIVES: To determine the clinical relevance of transurethral resection of the prostate (TURP) in patients with minor lower urinary tract symptoms (LUTS) but elevated prostate-specific antigen (PSA) levels. METHODS: We retrospectively included 82 patients, aged 50.2-78.2 yr, with minor LUTS, elevated PSA (> or =4 ng/ml), and no signs of prostate cancer (PCa) after (multiple) negative multisite biopsies who underwent TURP after they were diagnosed by urodynamics with bladder outlet obstruction (BOO). We evaluated the clinical benefit of TURP by assessing its effect on International Prostate Symptom Score (IPSS) and PSA and the diagnostic value of histologic examination of the resected tissue for the presence of PCa. RESULTS: After TURP, histologic analysis of the resected specimen revealed that eight patients (9.8%) had PCa; seven of these patients had a tumour that needed further treatment. The remaining 74 patients (90.2%) were diagnosed with BOO due to benign prostatic hyperplasia/benign prostatic enlargement (BPH/BPE). In this group, the mean PSA level decreased from 8.8 ng/ml before TURP to 1.1 ng/ml in the first year and 1.3 ng/ml in the second year after TURP; the mean IPSS decreased from 8.8 to 1.5 in the first year after TURP. CONCLUSIONS: The current data suggest that patients with minor LUTS and elevated PSA without evidence of PCa are very likely to have BOO due to BPH/BPE and may benefit from TURP if obstruction is proved. However, a prospective trial is warranted to assess the impact of these results on clinical practice.     

Botulinum toxin A treatment for lower urinary tract symptoms/benign prostatic hyperplasia

Botulinum toxin A (BoNT-A) has been widely used in the treatment of overactive bladder and neurogenic detrusor overactivity. Recently, prostatic injection of BoNT-A had been tried to reduce the prostate volume and relieve lower urinary tract symptoms (LUTS) in patients with benign prostatic enlargement (BPE) due to benign prostatic hyperplasia (BPH). However, the efficacy of BoNT-A on BPE is still controversial. Traditionally, male LUTS have been considered as synonym of BPE because most male LUTS developed in aging men. Recent investigations have revealed that bladder dysfunction and bladder outlet dysfunction other than BPE contribute equally in male LUTS. Injecting BoNT-A into the prostatic urethra and bladder neck yielded improvement of LUTS, but not reduction of the prostatic volume, especially in men with small prostatic volume. The therapeutic effects of BoNT-A on LUTS might not be due to prostatic volume reduction, but through inhibiting the adrenergic hyperactivity in men with LUTS/BPH. This article discusses the current consensus and controversy of BoNT-A treatment on LUTS/BPH.     

Overactive bladder in the male patient: bladder,outlet, or both?

Generations of urologists have presumed that the cause of lower urinary tract symptoms (LUTS) in men is infravesical (prostatic) obstruction. When symptoms such as urinary urgency and frequency can’t easily be explained directly by obstruction, secondary effects of obstruction on the bladder are identified as causative factors. Although to some extent this explanation may still be accurate, emerging concepts in the pathophysiology of LUTS in men may be at odds with these traditional explanations. The idea that primary bladder pathology may explain the symptom complex in at least one subset of men with LUTS has both experimental and clinical support. This review discusses the physiologic and clinical observations used to explain the mechanisms underlying LUTS. Specifically, this review focuses on two data sets: one supporting infravesical obstruction as the causative factor for LUTS, and another positing that a primary bladder abnormality is responsible.     

良性前列腺增生患者膀胱出口梗阻和逼尿肌功能的分析

目的：探讨尿动力学检查对BPH患者膀胱出口梗阻（BOO）和逼尿肌功能的诊断意义.方法：对95例BPH患者进行压力-容积和压力-流率测定.结果：95例BPH患者中BOO 57例,无BOO23例,其余15例为可疑或分析困难.BOO组前列腺体积大于无BOO组（62.4±16.1）cm^3 vs（41.0±7.1）cm^3（P＜0.05）,最大尿流率（Qmax）小于无BOO组（5.4±1.9）ml/s vs（12.4±5.0）ml/s（P＜0.05）,两组IPSS评分无差别（23.7±4.4）分vs（25.2±4.9）分（P＞0.05）.BOO组有逼尿肌不稳定收缩（DD34例,无BOO组D119例.结论：尿动力学检查有助于判断有无BOO存在,了解BPH患者的逼尿肌功能.IPSS不能判断患者的下尿路症状（LUTS）是否因BOO导致.BPH患者前列腺体积不足很大,但LUTS明显时,应行尿动力学检查.自由尿流率测定对BOO诊断有一定帮助.DI是无BOO患者发生LUTS的重要因素.     

Videourodynamic analysis in men with lower urinary tract symptoms: Correlation between age and prostate size with lower urinary tract dysfunction

ObjectivesLower urinary tract symptoms (LUTS) are highly prevalent in aging men. In this study we examined the relationship between age, total prostate volume (TPV), and videourodynamic study findings.MethodsWe retrospectively analyzed a total of 971 men ≥ 40 years of age referred to us for investigation of LUTS. We analyzed the distribution of the different videourodynamic study diagnoses in male LUTS by correlating their age and prostate size.ResultsThe most common diagnosis in the bladder outlet obstruction (BOO) group differed significantly by age and poor relaxation of the external sphincter (PRES) in those aged < 50 years; bladder neck dysfunction in those aged 50–69 years, and benign prostatic obstruction in those ≥ 60 years. Detrusor overactivity was the most common diagnosis in all ages in the bladder dysfunction group, and the cases of hyperactivity with impaired contractility (DHIC) increased with age. In patients < 50 years of age, PRES was the most common diagnosis in the BOO group in both those with small prostates (total prostate volume ≤ 40 mL) and large prostates (total prostate volume > 40 mL). In patients aged 50–69 years, the most common diagnosis in those with BOO and a small prostate was bladder neck dysfunction, and that in those with BOO and a large prostate was benign prostatic obstruction. Similar results were observed in patients aged ≥ 70 years. In all age groups, the majority of patients with detrusor overactivity, hypersensitive bladder, detrusor underactivity, and DHIC had a small prostate.ConclusionIn male LUTS, the diagnoses in the BOO group differed by age and prostate volume. In young patients with BOO, the leading diagnosis was PRES, and the contribution of prostate volume to BOO increased with age. As age increased, the bladder function became more complex with an increased percentage of patients with DHIC. Both bladder outlet and bladder functions were affected by age.     

Antimuscarinic therapy in men with lower urinary tract symptoms: What is the evidence?

Lower urinary tract symptoms (LUTS) in men have, until recently, been assumed to arise from bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia. Given this presumption, all manifestations (obstructive and irritative) of LUTS have been presumed to be responsive to therapy for prostatic disorders such as α-blockade (with or without the relatively recent addition of 5α-reductase inhibitors) or surgical intervention for benign prostatic hyperplasia. However, evidence demonstrates that persistence of irritative urinary symptoms is often encountered in men despite presumed adequate management of their obstructive complaints. Although antimuscarinic drugs have been found to be effective for irritative urinary symptoms attributed to the overactive bladder syndrome, concern regarding the use of this class of drugs in men with even potential coexistent BOO has limited the use of these drugs. Data are now accumulating that suggest that the antimuscarinic class may be used in men with bothersome, irritative symptoms, despite the presence of BOO (as defined by symptoms and urodynamics) and with a reasonable expectation of efficacy and little added risk. Critical evaluation of this evidence suggests that a role may exist for the antimuscarinic class in management of LUTS in men. However, areas of incomplete knowledge, including the risk associated with long-term (greater than 3 months) use of these drugs and the value of the antimuscarinic class as monotherapy in men with LUTS, still remain to be investigated.     

Vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia

α-Blockers, the current common treatment for lower urinary tract symptoms (LUTS), are also used to treat bladder outlet obstruction (BOO), but the effect is not as clinically significant as in LUTS. All currently marketed phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to significantly affect LUTS, although BOO-related efficacy has not been determined. Therefore, the extent of a causal relationship between LUTS and underlying benign prostatic enlargement (BPE) is questionable. LUTS may also be interpreted as symptoms related to detrusor overactivity, especially when no significant BOO is associated with BPE. Research is required to understand the efficacy of PDE5 inhibitors in LUTS but not in BOO. For vardenafil, nonclinical experiments and initial, preliminary clinical data suggest that the underlying effect may occur on the detrusor and not the prostate.     

Clinical guidelines for male lower urinary tract symptoms associated with non-neurogenic overactive bladder

The purpose of this guideline is to direct urologists and patients regarding how to identify overactive bladder (OAB) in male patients with lower urinary tract symptoms (LUTS) and to make an accurate diagnosis and establish treatment goals to improve the patients' quality of life (QoL). LUTS are commonly divided into storage, voiding, and postmicturition symptoms, and are highly prevalent in elderly men. LUTS can result from a complex interplay of pathophysiologic features that can include bladder dysfunction and bladder outlet dysfunction such as benign prostatic obstruction (BPO) or poor relaxation of the urethral sphincter. Diagnosis of OAB in male LUTS leads to accurate diagnosis of pure OAB and bladder outlet-related OAB, and appropriate treatment in men with residual storage symptoms after treatment for LUTS.     

Serum prostate-specific antigen to predict the presence of bladder outlet obstruction in men with urinary symptoms

OBJECTIVE: To determine whether prostate specific antigen (PSA) level can usefully predict or exclude bladder outlet obstruction (BOO), in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: A cohort of men from 1996 to 1999 who had LUTS caused by BPH was evaluated by serum PSA and pressure-flow urodynamic studies, and a blinded comparison made. The settings were teaching hospitals in London, UK and L'Aquila, Italy. Men (302) were referred by primary-care practitioners with LUTS and a PSA of < 10 ng/mL. Regression analysis was used to predict the extent of BOO, and create likelihood ratios and predictive values for BOO according to the PSA value. RESULTS: PSA was significantly associated with BOO (P < 0.001; r2 0.07), with significant likelihood ratios altering the probability of BOO. If the PSA was > 4 ng/mL, mild or definite BOO was likely (89%), whereas if the PSA was <2 ng/mL, there was about a one-third chance each of no, mild and definite BOO. CONCLUSION: High PSA levels in patients with LUTS are significantly associated with BOO; low PSA levels mean that definite BOO is unlikely.