多沙唑嗪能够改善BPH患者的ED症状

Actas Urol Esp,2004,28(4):290-297.勃起功能障碍(ED)是良性前列腺增生(BPH)常见的合并症,为了调查西班牙有中到重度下尿路症状的BPH患者中ED的患病率,以及探讨应用多沙唑嗪4mg/d治疗对ED症状的改善效果,Hernandez Fernandez等进行了一项开放、无对照、多中心的研究。从3901个     

良性前列腺增生组织中PDE5表达及其临床意义研究

良性前列腺增生症(BPH)是与年龄和雄激素相关的老年男性常见病、多发病.BPH的发生与患者的性功能减退密切相关[1].相关研究发现,用于治疗勃起功能障碍(ED)的磷酸二酯酶5型抑制剂(phosphodiesterase 5 inhibitors,PDE5i)可减轻大鼠动物模型膀胱出口梗阻(bladder outlet obstruction,BOO)症状,提示PDE5i治疗BPH导致下尿路症状的可能性[2].本文采用免疫组化技术检测PDE5在前列腺组织中的表达,并探讨其与临床资料的相关性.     

PDE5抑制剂治疗LUTS的进展及意义

勃起功能障碍及下尿路症状均为中老年男性常见疾病,多个流行病学研究证实二者密切相关。近年来多项研究证实PDE5抑制剂在改善ED患者勃起功能的同时,可有效改善患者的LUTS,但对患者的尿动力学指标无改善。本文就国内外ED与LUTS之间的联系、PDE5抑制剂治疗LUTs的进展及其可能的机制做一概述。     

良性前列腺增生/下尿路症状合并勃起功能障碍治疗的新靶点——PDE5

伴有下尿路症状(LUTS)的良性前列腺增生(BPH)是中老年男性常见病和多发病,其发病率随着年龄的增长而显著升高。研究表明,BPH/LUTS和勃起功能障碍(ED)之间密切相关,并对中老年男性的生活质量产生重要影响。磷酸二酯酶5抑制剂(PDE5i)在治疗ED的同时,可改善患者的BPH/LUTS,PDE5有望作为BPH/LUTS合并ED治疗的新靶点。对PDE5的结构、功能以及PDE5i的作用机制进一步探索,可为BPH/LUTS合并ED的临床治疗提供更加有效的策略。     

西地那非改善ED合并BPH患者的勃起功能以及下尿路症状

为了评估西地那非对男性勃起功能障碍(ED)合并良性前列腺增生(BPH)患者的勃起功能以及下尿路症状(LUTS)的治疗效果,McVary K等人进行了一项历时12周的双盲、安慰剂对照研究,研究入选     

BPH相关LUTS的临床特点及其对患者生活质量影响的研究

目的探讨良性前列腺增生症(BPH)患者出现下尿路症状(LUTS)的临床特点及其对患者生活质量的影响.方法对2003年7月至2009年10月收治的548例前列腺增生症患者的资料进行回顾性研究.分析患者住院时填写的国际前列腺症状问卷调查表(IPSS)、自行设计的夜尿症状评分表及性功能问卷调查表(MSF-4)上的数据.结果548例患者LUTS中,中度(8~19分)占24.8%,重度(20~35分)占75.2%.LUTS及其中各单个症状均与年龄存在正相关但相关性较小.LUTS及其中各单个症状与QoL正相关,症状评分越高,Q o L 评分也高.其中夜尿增多(Q 7)与Q o L 相关性最大,其次是排尿不尽(Q 1)、排尿无力(Q 5).28.6%(157/548)的患者认为夜尿增多对自己影响最大,主要影响患者的睡眠(NQ 5),其次是引起患者次日疲倦、注意力下降(NQ 1)及担心影响家人或伴侣的睡眠(NQ 6).经Spearman等级相关分析发现IPSS评分与性功能问卷(MSF-4评分)存在正相关(P<0.0001),其中夜尿增多、排尿困难及尿频是影响患者性功能最大的三个尿路症状(r=0.20648、0.20635、0.18861).结论 LUTS严重地影响BPH患者的生活质量,并影响患者的性功能.应重视对BPH患者夜尿增多的研究及其对患者睡眠及生活质量的影响.     

ED与LUTS药物治疗的相关性研究

目的探索、研究勃起功能障碍(ED)和下尿路症状(LUTS)在药物治疗方面是否存在相关性。方法本组研究对象80例病人均患有ED和LUTS,分为3组,每例研究对象在初诊时,必须填写IIEF-5、IPSS评分表,作为研究开始的基线。A组服用两地那非,B组服用多沙唑嗪控释片,C组联合应用西地那非和多沙唑嗪控释片。用药6个月后再次填写IIEF-5和IPSS评分表以作对比。用方差分析检验方法,进行用药前后数据统计学分析。结果3组治疗前后IIEF-5、IPSS评分变化差异均有编者计学意义,C组(联合用药组)变化最大(P<0.001)。结论ED与LUTS相互影响,ED患者LUTS发生率明显升高,而LUTS患者的ED危险性亦显著增加。西地那非可显著改善ED患者合并的LUTS症状,多沙唑嗪可改善LUTS患者的性功能;西地那非联合多沙唑嗪治疗ED、LUTS患者具协同作用。     

万艾可——一种治疗阴茎勃起障碍的新药

阴茎勃起功能障碍 (ＥＤ)是泌尿男科常见病之一 ,发病率约 10 % [1] 。在美国约 30 0 0万人患ＥＤ ,每年 4 0 0万门诊患者 ,30万人需要住院治疗。治疗ＥＤ的有效方法主要包括 :负压吸引、血管活性药物阴茎海绵体内注射、前列腺素Ｅ1尿道内灌注、假体植入及一些动静脉手术等 ,多存在一定的副作用 ,不方便 ,不接近自然状态 ,不易为患者接受 ,退出率较高[2 ] 。万艾可 (Ｖｉａｇｒａ)是一种磷酸二酯酶Ｖ (Ｐｈｏｓ ｐｈｏｄｉｅｓｔｅｒａｓｅＴｙｐｅＶ ,ＰＤＥ5)的拮抗剂 ,是第一个通过ＦＤＡ用于治疗ＥＤ的口服药物 ,疗效佳、副作用少、使用…     

PDE5在ED治疗中的靶向作用

作为细胞内信号传导的第二信使，cAMP和cGMP在细胞的生命活动中有重要的意义，细胞内cAMP和cGMP水平的调控是由环化酶的合成和磷酸二酯酶（PDEs）的水解作用来实现。PDEs能特异性地催化环嘌呤核苷酸的3’，5’-磷酸二酯键，水解生成相应的无活性的5’-GMP或5’-AMP。自1962年Sulherland和Rall首次发现别对细胞内第二信使cGMP和cAMP具有水解活性的PDE以来。     

万艾可治疗老年糖尿病性勃起功能障碍疗效分析

目的:观察万艾可治疗我国老年糖尿病性勃起功能障碍患者的临床安全性和疗效。方法:用国际勃起功能问卷的勃起功能评分、性生活日记的问题2及问题3和总体评价问卷评估452例患者服用万艾可前后勃起功能状况。结果:服药后,患者的国际勃起功能问卷的勃起功能评分提高程度、性生活日记问题2和问题3作肯定回答的患者百分率,以及总体评价问卷回答百分率均显著高于基线值,统计学分析差异有极显著性(P<0.01)。结论:万艾可显著改善糖尿病性勃起功能障碍患者的勃起能力,提高性生活质量。     

速尿联合多沙唑嗪治疗BPH/LUTS患者夜尿增多的研究

目的:探讨速尿联合多沙唑嗪治疗BPH/LUTS患者夜尿增多的疗效及安全性。方法:将64例BPH/LUTS夜尿增多患者随机均分为两组,一组患者给予多沙唑嗪(4 mg/d),另一组患者给予速尿(睡前6 h40 mg)联合多沙唑嗪,两组患者分别治疗4周后,记录并分析治疗前后患者的尿量、IPSS评分、QOL评分、血电解质和血浆渗透压变化情况。结果:速尿联合多沙唑嗪组与单用多沙唑嗪组比较,夜尿次数明显减少(P<0.01),白天尿量增加(P<0.01),夜间尿量减少(P<0.01),总尿量无明显改变(P>0.05),IPSS评分下降(P<0.05),QOL评分明显下降(P<0.01),血钠、钾、氯、渗透压无明显变化(P>0.05)。结论:速尿联合多沙唑嗪治疗BPH/LUTS患者夜尿增多的疗效明显,4周的治疗是安全的。     

良性前列腺增生与下尿路症状及急性尿潴留的关系

目的　探讨前列腺移行带增生与下尿路症状 (LUTS)及急性尿潴留 (AUR)的关系。方法　将 119例良性前列腺增生(BPH)患者按有无AUR及LUTS严重程度分为 3组 :无AUR但LUTS较重者为A组 ,有AUR且LUTS较重者为B组 ,有AUR但LUTS较轻者为C组。对各组行I PSS评分 ,测量F PSA、T PSA及F/T PSA ;耻骨上经膀胱切除前列腺时观察移行带向膀胱内突出情况及前列腺部尿道狭窄情况 ,术后测定移行带质量 (TZW ) ,计算移行带体积 (TZV)。结果　各组F/T PSA、TZW、TZV差别无统计学意义 (P >0 .0 5 )。A、B两组I PSS评分及前列腺部尿道狭窄百分比明显高于C组 (P <0 .0 5 ) ;A组F PSA、T PSA、移行带向膀胱内突出百分比明显低于C组 (P <0 .0 5 ) ,而B、C两组这 3项指标无明显差异 (P >0 .0 5 )。A组F PSA、T PSA明显小于B组 (P <0 .0 0 1) ,I PSS、前列腺部尿道狭窄及移行带向膀胱内突出百分比与B组无显著性差异 (P >0 .0 5 )。结论　前列腺移行带质量及体积与BPH引起的LUTS及AUR的发生无关 ;而移行带的增生使前列腺部尿道狭窄、延长是BPH引起的LUTS的主要原因 ;移行带向膀胱突出则是AUR的主要原因。BPH合并AUR的患者F PSA及T PSA均明显增高 ,F/T PSA变化则不明显。     

合并组织学前列腺炎的良性前列腺增生患者TURP手术对下尿路症状的影响

目的:探讨合并组织学前列腺炎的良性前列腺增生(BPH)患者行经尿道前列腺电切术(TURP)对下尿路症状的影响。方法:对2009年5月至2011年5月行TURP术后病理诊断证实为BPH的432例患者进行研究。剔除术前和术后合并有影响下尿路症状因素的病例,参照国际前列腺炎组织学分类诊断标准,分为A组:单纯BPH组(30例)、B组:合并轻度炎症组(55例)、C组:合并中度炎症组(31例)、D组:合并重度炎症组(28例)。采取国际前列腺症状评分(IPSS)评估各组术前及术后1个月的下尿路症状,将得分进行统计学分析。结果:合并组织学前列腺炎患者399例,检出率为92.4%。其中轻度炎症组269例(67.4%)、中度炎症组86例(21.6%)、重度炎症组44例(11.0%)。术前各组IPSS评分为:A组(21.43±6.09)分、B组(21.75±5.97)分、C组(27.84±4.18)分、D组(31.00±2.92)分,仅A组和B组差异无统计学意义(P=1.000),其余各组间差异均有统计学意义(P值均<0.01)。术后各组IPSS评分为:A组(5.60±2.16)分、B组(7.36±2.77)分、C组(11.55±3.39)分、D组(16.89±3.37)分,各组间差异均有统计学意义(P值均<0.01)。手术治疗后各组IPSS评分均较术前明显降低,差异有统计学意义(P值均<0.01)。合并炎症的BPH患者的病理切片中浸润的炎性细胞几乎均为淋巴细胞。结论:BPH大都合并有组织学慢性前列腺炎。合并组织学炎症的BPH患者手术前和手术后的下尿路症状严重程度要高于无炎症的BPH患者,且与炎症分级程度呈正相关。对合并中、重度炎症患者,术后仍需积极运用药物控制下尿路症状。     

Effect of tamsulosin on ejaculatory function in BPH/LUTS

This study was undertaken to determine the impact on ejaculatory function of tamsulosin (0.2 mg) given once daily (OD) for 12 weeks and to identify risk factors for ejaculatory dysfunction in patients undergoing this treatment. Males with an International Prostatic Symptom Score (IPSS) ≥8 were enrolled in this study. All participants completed questionnaires, including the IPSS and the Male Sexual Health Questionnaire (MSHQ), and serum prostate-specific antigen, transrectal ultrasound and uroflowmetry with post-void residual were measured. After initiating 0.2 mg OD tamsulosin, patients were re-evaluated on the fourth and twelfth weeks of medication. The chi-squared test, the independent t-test and one-way ANOVA were used to compare means. Binary logistic regression analysis was used to calculate the odds ratio for all risk factors. A total of 177 men constituted the study cohort. No significant difference was observed between baseline and follow-up for the erectile function, ejaculatory function, satisfaction, sexual activity and desire domains (EFD, EjFD, SDA and ADD) or for erectile or ejaculatory bother mean scores. After 12 weeks, the overall incidence of ejaculatory dysfunction (EjD) was 13.4%. Incidences of the seven different types of EjD (decreased frequency, delay, dryness, decreased strength/force, decreased volume, decreased pleasure and pain at ejaculation) were 2.4%, 3.1%, 3.9%, 3.9%, 6.3%, 7.1% and 3.1%, respectively. Baseline EjFD scores were higher for IPSS responders than for non-responders (26.09 vs. 24.06, P=0.03). An EjFD score reduction was more frequent in IPSS responders. The incidence of EjD was small, but not negligible and was more frequent in patients with less lower urinary tract symptoms, a smaller prostate, higher baseline MSHQ totals and higher EjFD scores.     

Impacts of medical treatments for lower urinary tract symptoms suggestive to benign prostatic hyperplasia on male sexual functions

Although alpha blockers with or without 5-alpha reductase inhibitors (5-ARIs) have become the standard of treatment for men with moderate to severe lower urinary tract symptoms suggestive to benign prostatic hyperplasia (LUTS/BPH), their negative adverse effects on male sexual functions have become another major issue, which may have a direct impact on patients' quality of life and overall satisfaction. Erectile dysfunction, ejaculation disorders, reduced libido, or anorgasmia have been noted among patients receiving these standards of treatments and these adverse events may be irreversible even after discontinuation of medications. Physicians should inform and discuss with their patients about these potential side effects before prescribing these medications for their LUTS/BPH treatment. Tadalafil is the first phosphodiesterase type 5 inhibitor which has the indications for LUTS/BPH and erectile dysfunction and its efficacy is comparable to alpha-blockers with regards to the reduction of LUTS and improvement of quality of life. Moreover, early clinical studies have showed that the combination use tadalafil with alpha blockers or 5-ARIs may have an additional benefit on symptom relief and maximum urinary flow rate (Q_max) improvement. As expected, the improvement on erectile function is significant, especially among patients taking 5-ARIs regularly. Although there are promising data from the combination use of tadalafil with 5-ARIs or tadalafil with alpha-blockers, more large-scale clinical studies are still needed to confirm their long term safety and efficacy profiles.     

A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS

Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so-called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre-clinical pharmacological testing and large-scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor-mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor-mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short-term clinical efficacy, set the stage for a large-scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms.     

A new experimental rat model of erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: the testosterone‐supplemented spontaneously hypertensive rat

What's known on the subject? and What does the study add? Lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are common problems in the aging male population. Moreover, several recent studies have shown that ED is closely associated with the presence and severity of LUTS independently of co‐morbidities. However, the pathophysiological mechanisms linking LUTS/BPH and ED remain largely unexplored. The major difficulty in studying such relationships between ED and LUTS/BPH, and of exploring the impact of new therapeutic approaches for both LUTS/BPH and ED, is the lack of experimental model combining ED, prostate enlargement and bladder dysfunction all at once. The present study describes a new model of BPH, the SHR supplemented with testosterone which is the first animal model which displays all at once the key features of BPH: prostate enlargement and an increased sympathetic tone of bladder outlet mimicking the static and the dynamic components of voiding symptoms of BPH, a significant impairment of bladder function which reflects the storage symptoms of BPH and finally, ED. This model could be very relevant to better characterize the close relationship that exists between BPH/LUTS and ED, and to evaluate new therapeutic strategies for BPH together with their side effect profile on sexual function on the same animal, thus allowing a reduction of the number of animals to be used in such studies. Study Type – Aetiology (case control) Level of Evidence 3b

OBJECTIVE

• ? To design a new experimental model combining erectile dysfunction, prostate enlargement and urodynamic impairment characteristic of lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH).

MATERIALS AND METHODS

• ? Three groups of animals (12‐week‐old; n= 7/group) were considered: Wistar Kyoto (control) rats (WKY), untreated spontaneously hypertensive rats (SHR) and SHR treated with testosterone (SHR‐T, 3 mg/kg/day) for 3 weeks.
• ? Cystometry experiments and evaluation of erectile function were performed. Prostate enlargement was evaluated.

RESULTS

• ? SHR displayed a significant decrease in the intercontraction interval (ICI) and in the voided volume (VV) whereas non‐voiding contractions (NVC) were increased. SHR‐T exhibited a further decreased ICI and VV and an increased frequency of NVC.
• ? Erectile responses to electrical stimulation of the cavernous nerve were significantly impaired in both SHR (?66%) and SHR‐T (?58%).
• ? The prostate weight was similar in WKY and SHR, but significantly increased in SHR‐T.

CONCLUSIONS

• ? The testosterone‐supplemented SHR represents an experimental model for urodynamic impairment combining both static and dynamic components of voiding symptoms with erectile dysfunction and prostate enlargement.
• ? This model is suitable for the assessment of sexual side effects of LUTS/BPH treatments and efficacy of new therapeutic agents in LUTS/BPH and associated erectile dysfunction.

     

Common approach to managing lower urinary tract symptoms and erectile dysfunction

The present paper serves as a review of the associations between lower urinary tract symptoms （LUTS） and erectile dysfunction （ED）, with a focus on common and combined pathways for treatment. LUTS and ED are common conditions seen in general urologic practice. Research has started to establish epidemiologic and pathophysiologic links between the two conditions and a strong association confirmed across multiple studies. Men seeking care for one condition should always be interviewed for complaints of the other condition. Proposed common pathways include α-1 adrenergic receptor imbalance, Rho-kinase overactivity, endothelial cell dysfunction and atherosclerosis-induced ischemia. Medical therapy has replaced surgery as the first-line treatment for LUTS in most patients, with the incorporation of α-adrenergic receptor antagonists （α-ARAs） and 5-α-reductase inhibitors （5-ARIs） into everyday practice. Treatment with α-ARAs contributes to some improvement in ED, whereas use of 5-ARIs results in worsened sexual function in some patients. Phosphodiesterase-5 （PDE-5） inhibitors have revolutionized the treatment of ED with a simple oral regimen, and new insights demonstrate a benefit of combined use of PDE-5 inhibitors and α-ARAs. The mechanisms of action of these medications support these observed benefits, and they are being studied in the basic science and clinical settings. In addition, novel mechanisms for therapy have been proposed based on clinical and research observations. The minimally invasive and surgical treatments for LUTS are known to have adverse effects on ejaculatory function, while their effects on erectile function are still debated. Much remains to be investigated, but it is clear that the associations between LUTS and ED lay the foundation for future therapies and possible preventative strategies.