后尿道—球海绵体反射在原发性早泄及射精迟缓发病机制中的研究
|
摘要
研究背景
早泄是最常见的男子性功能障碍性疾病,全球发病率高达9%-31%,主要分为原发性早泄和继发性早泄。其中,原发性早泄的发病率低于继发性早泄,但其具体的发病率尚难以确定。根据国际性医学学会(ISSM)的最新定义,原发性早泄需具备以下特征：阴道内射精潜伏期(IELT)总是或几乎总是小于1分钟；缺乏随意控制射精的能力；导致一些负面的影响,如忧虑、烦恼、沮丧或／和回避性生活等。由于约有10%的原发性早泄患者阴道内射精潜伏期介于1-2分钟之间,因此,射精潜伏期的临界值并非严格规定为1分钟。
尽管越来越多的因素如心理性因素、中枢5-羟色胺能神经介质传递紊乱、基因易感性、阴茎高敏感性、异常的体感诱发电位以及增强的阴茎-大脑皮质反射等被报道与原发性的早泄的病因相关,但由于难以建立原发性早泄的动物模型,相关的研究只能通过临床试验进行,导致研究滞后,发病机制尚不明确,给临床分类诊断及分类治疗带来了困难,难以达到理想的治疗效果。现代医学认为,射精的生理过程是包括泌精过程、射精和性高潮的一系列神经反射过程。在性兴奋期,精液分泌至前列腺部后尿道,此时尿道外括约肌紧张性收缩以防止精液流出,促使后尿道内压增高,产生前列腺尿道压力室效应,而诱发射精紧迫感及尿道周围肌群(球海绵体肌、坐骨海绵体肌等)阵挛性收缩并将精液排出尿道.由此可见,正是前列腺部后尿道压力室效应的形成最终诱发了射精。球海绵体肌又称“射精肌”,是位于球部尿道的一对横纹肌,受会阴神经支配,其收缩可增加尿道内压力,阵挛性收缩将精液排出体外。因此探讨前列腺部后尿道-球海绵体反射在射精功能障碍发病机制中的作用具有重要的意义。基于上述研究及理论基础,我们自主发明了一种尿道电刺激电极,在国内外首次将其应用于原发性早泄发病机制的研究,通过诱发前列腺部后尿道-球海绵体反射,同时结合龟头生物感觉阈值测定探讨原发性早泄的发病机制。
目的
探讨前列腺部后尿道-球海绵体反射(BCR)在原发性早泄(PPE)发病机制中的作用。
方法
自2007年9月至2009年3月,从山东大学齐鲁医院泌尿外科门诊筛选42名符合条件的原发性早泄患者,组成原发性早泄组。从劳务市场招募并筛选20名符合条件的男性健康志愿者,组成健康对照组。该研究获得山东大学齐鲁医院伦理委员会批准。每位入选者均被详细的告知该研究的目的、方法以及操作可能带来的并发症,并在完全自愿的条件下签署知情同意书。
原发性早泄组患者：结婚一年以上或有固定的性伴侣一年以上,年龄24-37岁,平均年龄29.6岁,平均身高172.6cm,检查前一个月内至少4次射精(每两次间隔大于24h),平均计时IELT小于2分钟。自述控制射精的能力差,并因此导致个体忧虑、烦恼、沮丧或／和回避性生活等负面影响。
健康对照组：结婚一年以上或有固定的性伴侣一年以上,年龄23-38岁,平均年龄30.8岁,平均身高171.7cm。均自述有良好的控制射精的能力。因计时IELT难以在志愿者中执行,我们采用自我评估IELT,平均IELT大于4分钟。两组受试者间年龄及身高无统计学差异(P>0.05)。
对所有受试者行国际勃起功能评分问卷-5(IIEF-5),排除阴茎勃起功能障碍。行尿液常规和前列腺液常规排除泌尿系统感染。通过问诊及测血压、血糖排除高血压、糖尿病、酒精依赖症、冠心病等系统性疾病。入选前一个月内未曾服用影响射精功能的药物。通过《明尼苏达多项人格测验-Ⅱ》(MMPI-II)排除明显的精神障碍。
在24摄氏度室温环境下,受试者排尿后,仰卧在检查床上。应用美敦力肌电图诱发电位仪(Medtronic Keypoint,丹麦),分别行龟头敏感度检测以及前列腺部后尿道-球海绵体反射。
龟头敏感度检测：生理盐水清洁龟头表面,将两个表面电极分别置于龟头两侧。将矩形电流脉冲持续时间调整为0.04ms,频率调整为3Hz,从OmA逐渐增加电流强度,直至受试者述可感知龟头部轻微针刺样刺激,记录此时刺激量。然后逐渐减小电流强度,直至受试者述刚刚不能感知上述刺激,再次记录刺激量。重复三次,取平均值,即为该受试者者的龟头生物感觉阈值。
前列腺部后尿道-球海绵体反射：将我们自主发明制作的后尿道电刺激电极应用于诱发前列腺部后尿道-球海绵体反射。正负两个环状电极相距1.5cm,附着在一根14F Foley双腔导尿管远端,其中负极位于正极远端,距离球囊边缘lcm。使用前应用万福金安消毒液浸泡30分钟,并用无菌生理盐水冲洗。应用碘伏对受试者会阴部进行消毒,将后尿道电刺激电极经尿道置入膀胱,球囊内注入l0ml生理盐水,然后轻轻牵拉导尿管,以使两个环状电极位于前列腺后尿道部。球海绵体肌(BC)部应用碘伏皮肤消毒,将一同心圆针电极经皮刺入受试者一侧球海绵体肌。调至H-reflex模式,将矩形电流脉冲持续时间调整为0.2ms,频率调整为1Hz,从OmA开始逐渐增加电流强度,直至受试者述有轻微的球海绵体肌部跳动感,记录此时的刺激量。此时,将手指置于球海绵体肌部触诊可触及轻微的跳动感,同心圆针状电极可记录到肌电活动,但潜伏期极不稳定。将刺激量逐渐减小,直至受试者刚刚不能感知上述跳动感,再次记录此时阈值。重复上述操作三次,求平均值即为前列腺部后尿道-球海绵体反射感觉阈值。逐渐增加前列腺部后尿道电刺激量,直至通过同心圆针电极可记录到具有恒定潜伏期的前列腺部后尿道-球海绵体反射,此时可触诊及强烈的球海绵体肌部跳动,记录此时的刺激阈值,并通过叠加技术测定反射潜伏期。
采用SPSS 16.0统计软件,对两组数据应用正态性检验、成组设计的Student t检验以及Pearson相关性分析。P<0.05为差异有统计学意义。原发性早泄组数据以偏离正常组平均值1.96倍的标准差为异常。
结果
通过电刺激前列腺部后尿道,在所有受试者中均可诱发出球海绵体反射。在感觉阈值的刺激下,这种反射的波幅较低且潜伏期不稳定。随着刺激强度的增大,在大约两倍感觉阈值刺激下,可诱发出具有恒定潜伏期的波形,且具有较高的波幅。然而在同一固定刺激下(足以诱发恒定的球海绵体反射),波幅在不同受试者之间差异较大,且在同一受试者,随同心圆针电极在球海绵体肌的位置不同而变化,因此未作为一项参数进行记录。
在正常对照组,平均后尿道感觉阈值、诱发恒定反射阈值、反射潜伏期以及平均龟头生物感觉阈值分别为18.20+/-2.68mA(0.2ms, 1Hz)、34.76+/-4.15mA (0.2ms, 1Hz)、71.2+/-5.77ms和14.16+/-1.94mA (0.04ms,3Hz).而在原发性早泄组分别为12.38+/-3.71mA (0.2ms, 1Hz),23.81+/-5.55mA (0.2ms, 1Hz), 70.48+/-6.33ms和11.89+/-2.26mA (0.04ms,3Hz)。其中,原发性早泄组后尿道感觉阈值、诱发恒定反射阈值以及龟头生物感觉阈值均小于正常对照组,有统计学差异(P<0.001)。而两组间前列腺部后尿道-球海绵体反射潜伏期无统计学差异(P>0.05)。
数据表明,42名原发性早泄患者中,29名患者前列腺部后尿道-球海绵体反射感觉阈值低于正常参考值,占69%；31名患者诱发恒定反射阈值低于正常参考值,占74%,其中两名患者反射感觉阈值在正常范围。然而,仅有10名患者龟头生物感觉阈值低于正常参考值,占24%,其中有9名同时伴有异常的前列腺部后尿道-球海绵体反射感觉阈值及诱发恒定反射阈值。
相关性分析显示,两组受试者前列腺部后尿道-球海绵体反射感觉阈值及诱发恒定反射阈值均存在显著正相关,其中原发性早泄组,r=0.946,P<0.001,对照组r=0.893,P<0.001.然而,龟头生物感觉阈值与前列腺部后尿道-球海绵体反射感觉阈值以及诱发恒定反射阈值均无相关性(P>0.05)。另外,年龄与上述所有参数未见相关性(P>0.05)。
该研究具有良好的安全性,通过检查后多饮水及短期口服抗生素,所有受试者除一过性尿频外,未出现尿路感染以及尿道狭窄等其他并发症。
结论
原发性早泄患者存在高兴奋性的前列腺部后尿道-球海绵体反射,这可能在原发性早泄的发病机制具有重要的作用,同时也为探讨其他有效的治疗方法提供了新的途径。
研究背景
射精迟缓是一种相对少见的男性射精功能功能障碍。上世纪90年代的的人群调查显示其发病率介于0至3%之间。一项针对年龄16至44岁英国男性的研究结果显示,在5000名被调查者中有5.3%的男性在过去的一年中至少有一个月的时间存在射精迟缓或不射精,而仅有2.9%的男性在过去的一年中至少有6个月存在射精迟缓或不射精。精神疾病诊断与统计手册(DSM)将射精迟缓定义为：在足够的性刺激下,男性出现持续或反复的性高潮延迟或缺失,从而给个体带来忧虑的射精功能障碍。射精迟缓分为原发性和继发性,频发性或偶发性。
射精迟缓随男性年龄的增长,发病率随之增加。在男性的二十至三十岁期间,外周快速传导感觉神经元的进展性丧失变的日趋明显。同时,年长男性出现的表皮萎缩、髓鞘胶原的浸润和环形小体的变性,可能导致一定程度的年龄相关的阴茎退化性低麻醉状态,从而难以达到射精所需的阈值。
除年龄外,研究表明生理因素、先天性和解剖原因、,骨盆区手术包括根治性前列腺切除术、经尿道前列腺电切术和膀胱颈部手术等、药物性因素如左旋多巴、噻嗪类利尿剂、5-羟色胺再摄取抑制剂和三环类抗抑郁药、吩噻嗪和酒精等、脊髓损伤和多发性硬化(MS)等神经性因素、糖尿病和几乎所有的心理问题都可能导致射精迟缓。但其具体的发病机制却并不明确。现代医学认为,射精的生理过程是包括泌精过程、射精和性高潮的一系列神经反射过程。在性兴奋期,精液分泌至前列腺部后尿道,此时尿道外括约肌紧张性收缩以防止精液流出,促使后尿道内压增高,产生前列腺尿道压力室效应,而诱发射精紧迫感及尿道周围肌群(球海绵体肌、坐骨海绵体肌等)阵挛性收缩并将精液排出尿道.由此可见,正是前列腺部后尿道压力室效应的形成最终诱发了射精。球海绵体肌又称“射精肌”,是位于球部尿道的一对横纹肌,受会阴神经支配,其收缩可增加尿道内压力,阵挛性收缩将精液排出体外。因此探讨前列腺部后尿道-球海绵体反射在射精功能障碍发病机制中的作用具有重要的意义。基于上述研究及理论基础,我们自主发明了一种尿道电刺激电极,在国内外首次将其应用于射精迟缓发病机制的研究,通过诱发前列腺部后尿道-球海绵体反射,同时结合龟头生物感觉阈值测定探讨射精迟缓的发病机制。
目的
探讨前列腺部后尿道-球海绵体反射(BCR)在射精迟缓(RE)发病机制中的作用。
方法
自2007年9月至2009年3月,从山东大学齐鲁医院泌尿外科门诊筛选5名符合条件的射精迟缓患者,组成射精迟缓组。从劳务市场招募并筛选20名符合条件的男性健康志愿者,组成健康对照组。该研究获得山东大学齐鲁医院伦理委员会批准。每位入选者均被详细的告知该研究的目的、方法以及操作可能带来的并发症,并在完全自愿的条件下签署知情同意书。
射精迟缓组患者：结婚一年以上或有固定的性伴侣一年以上,年龄26～32岁,平均年龄28.8岁,平均身高172.5cm,在过去一年内经常出现射精迟缓,甚至不射精,平均IELT大于30分钟,并因此导致患者本人或其性伴侣、烦恼、沮丧或／和回避性生活等负面影响,并主动寻求治疗。
健康对照组：结婚一年以上或有固定的性伴侣一年以上,年龄23～38岁,平均年龄30.8岁,平均身高171.7cm。均自述有良好的控制射精的能力和满意的性生活。平均IELT大于4分钟。两组受试者间年龄及身高无统计学差异(P>0.05)。
对所有受试者行国际勃起功能评分问卷-5(IIEF-5),排除阴茎勃起功能障碍。行尿液常规和前列腺液常规排除泌尿系统感染。通过问诊及测血压、血糖排除高血压、糖尿病、酒精依赖症、冠心病等系统性疾病。入选前一个月内未曾服用影响射精功能的药物。通过《明尼苏达多项人格测验-Ⅱ》(MMPI-II)排除明显的精神障碍。
在24摄氏度室温环境下,受试者排尿后,仰卧在检查床上。应用美敦力肌电图诱发电位仪(Medtronic Keypoint,丹麦),分别行龟头敏感度检测以及前列腺部后尿道-球海绵体反射。
龟头敏感度检测：生理盐水清洁龟头表面,将两个表面电极(丹迪13L020,丹麦)分别置于龟头两侧。将矩形电流脉冲持续时间调整为0.04ms,频率调整为3Hz,从OmA逐渐增加电流强度,直至受试者述可感知龟头部轻微针刺样刺激,记录此时刺激量。然后逐渐减小电流强度,直至受试者述刚刚不能感知上述刺激,再次记录刺激量。重复三次,取平均值,即为该受试者的龟头生物感觉阈值。
前列腺部后尿道-球海绵体反射：将我们自主发明制作的后尿道电刺激电极应用于诱发前列腺部后尿道-球海绵体反射。正负两个环状电极相距1.5cm,附着在一根14F Foley双腔导尿管远端,其中负极位于正极远端,距离球囊边缘1cm。使用前应用万福金安消毒液浸泡30分钟,并用无菌生理盐水冲洗。应用碘伏对受试者会阴部进行消毒,将后尿道电刺激电极经尿道置入膀胱,球囊内注入10ml生理盐水,然后轻轻牵拉导尿管,以使两个环状电极位于前列腺后尿道部。球海绵体肌(BC)部应用碘伏皮肤消毒,将一同心圆针电极(丹迪DCN37,丹麦)经皮刺入受试者一侧球海绵体肌。调至H-reflex模式,将矩形电流脉冲持续时间调整为0.2ms,频率调整为1Hz,从OmA开始逐渐增加电流强度,直至受试者述有轻微的球海绵体肌部跳动感,记录此时的刺激量。此时,将手指置于球海绵体肌部触诊可触及轻微的跳动感,同心圆针状电极可记录到肌电活动,但潜伏期极不稳定。将刺激量逐渐减小,直至受试者刚刚不能感知上述跳动感,再次记录此时阈值。重复上述操作三次,求平均值即为前列腺部后尿道-球海绵体反射感觉阈值。逐渐增加前列腺部后尿道电刺激量(为保证受试者安全,最高电刺激量定为80mA),直至通过同心圆针电极可记录到具有恒定潜伏期的前列腺部后尿道-球海绵体反射,此时可触诊及强烈的球海绵体肌部跳动,记录此时的刺激阈值,并通过叠加技术测定反射潜伏期。射精迟缓组数据以偏离正常对照组平均值1.96倍的标准差为异常。
结果
通过电刺激前列腺部后尿道,在所有受试者中均可诱发出球海绵体反射。在正常对照组,在感觉阈值的刺激下,这种反射的波幅较低且潜伏期不稳定,随着刺激强度的增大,在大约两倍感觉阈值刺激下,可诱发出具有恒定潜伏期的波形,且具有较高的波幅。然而在同一固定刺激下(足以诱发恒定的球海绵体反射),波幅在不同受试者之间差异较大,且在同一受试者,随同心圆针电极在球海绵体肌的位置不同而变化,因此未作为一项参数进行记录。在射精迟缓组,在80mA(0.2ms, 1Hz)电刺激下(最大安全电刺激量),均未诱发出恒定的前列腺部后尿道-球海绵体反射。
正常对照组后尿道感觉阈值、诱发恒定反射阈值、反射潜伏期以及龟头生物感觉阈值分别为18.20+/-2.68mA (0.2ms, 1Hz)、34.76+/-4.15mA (0.2ms, 1Hz)、71.20+/-5.77ms和14.16+/-1.94mA (0.04ms,3Hz)。射精迟缓组后尿道感觉阈值分别为40.20mA、46.45 mA、60.37 mA、51.96 mA和55.26 mA (0.2ms, 1Hz),对应的龟头生物感觉阈值分别为19.30 mA、15.75 mA、14.82 mA、15.27 mA以及13.63mA。射精迟缓组后尿道感觉阈值明显高于正常对照组,龟头生物感觉阈值与对照组无明显差别。
该研究具有良好的安全性,通过检查后多饮水及短期口服抗生素,所有受试者除一过性尿频外,未出现尿路感染以及尿道狭窄等其他并发症。
结论
射精迟缓患者存在低兴奋性的前列腺部后尿道-球海绵体反射,这可能在射精迟缓的发病机制中具有重要的作用。
Background
Premature ejaculation (PE) is the most common sexual dysfunction all over the world with a prevalence ranging from 9% to 31% of the general male population.It may be mainly divided into lifelong PE and acquired PE.While the incidence of lifelong PE is believed to be much smaller despite it hasn't been reliably determined. According to the ISSM(the International Society for Sexual Medicine) definition of lifelong PE,it is characterized by ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration,the inability to delay ejaculation on all or nearly all vaginal penetrations,and with negative personal consequences,such as distress,bother,frustration,and/or the avoidance of sexual intimacy. While the 1-minute IELT cutoff point should not be applied in the most absolute sense,as about 10% of men seeking treatment for lifelong PE have IELTs of 1-2 minutes.
More and more factors such as psychological factors,disturbance of central serotoninergic neurotransmission,genetic vulnerability,penile hypersensitivity, abnormal somatosensory evoked potentials, greater cortical penile representation and so on have been reported to be related to the etiology of lifelong PE.While because it is very hard to establish the animal model of lifelong PE,the related research could only be carried by clinical trials,which results in the unclear mechanism,and makes diagnosis and therapy difficult. Based on the theory that the sense of "ejaculatory inevitability" occurs in response to distention of the posterior urethra and finally results in pulsatile contractions of periurethral musculature which propel the seminal fluid through the urethra,we invented and designed a special transurethral electrode to study the relationship between bulbocavernosus reflex (BCR) to stimulation of prostatic urethra and lifelong PE, which had never been studied before. Also, sensitivity of glans penis to electrical stimulation was recorded.
Objective
In our study the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and primary premature ejaculation was studied.
Methods
From September 2007 to March 2009,forty-two patients(mean age 29.6 years,range from 24 to 37,mean height 172.6cm)complaining of lifelong PE from our out-patient department of urology and twenty normal potent volunteers (mean age 30.8years,range from 23 to 38,mean height 171.7cm) from labour market were involved in this prospective,case-control study which had been approved by the local ethics committee and all the subjects provided informed consent. All the forty-two patients complaining of unsatisfactory intercourse with poor control over ejaculation and average stopwatch IELT(intravaginal ejaculation latency time) within 2 minutes (38 of them within 1 minute)were classified as the lifelong PE group and all the normal potent men who presented satisfactory sexual intercourse and good control over ejaculation with the average estimated IELT more than 4 minutes were classified as the control group,for the stopwatch IELT was hard to be obtained in the healthy controls. Baseline stopwatch IELT was measured for the 4-week baseline period during which patients were asked to have at least four intercourses at least 24 hours apart.Every subject had marriage history of more than one year. Except for lifelong PE,none of the patients complained of any other diseases and all the controls were healthy volunteers. They were all free of genitourinary tract infection,erectile dysfunction, systemic(diabetes, alcoholism, hypertension and so on,as well as continuous drug use of selective serotonin reuptake inhibitors (SSRIs),alpha blockers and phosphodiesterase-5 (PDE-5) inhibitors et al that might affect sexual activities by detailed medical and sexual history and comprehensive examinations such as routine tests of urine and expressed prostatic secretions and IIEF-5(international index of erectile function of five items)questionaire and so on.Moreover,all the subjects didn't have depressive or anxiety disorder,dysthemia,suicidality,(hypo)manic episode,panic disorder,agoraphobia,social phobia,obsessive-compulsive disorder posttraumatic stress disorder or psychotic disorders excluded by MMPI-II(Minnesota Multiphasic Personality Inventory-Ⅱ).Therefore,comorbidity index wasn't used in our study.Besides, for limitation of some objective reasons,Meares-Stamey test which would be better for assessment of genitourinary tract infection wasn't performed.Hence, it might have mild effect to the enrollment of the subjects.In addition, for the electrical examinations on human beings,only height was highlighted,so we ignored the influence of weight to the outcome measures. And only the subjects'height reported by themselves was recorded in this study.There was no statistically significant differences in age and height between the two groups(P>0.05).
The electrical physiological recordings were performed by using a Medtronic Keypoint Electromyograph(Dantec Medical A/S,Skovlunde,Denmark) and during the course each subject was placed supine in a quiet examining room at 24℃after emptying the bladder.
Sensitivity of the glans penis was detected by electrical stimulation (rectangular pulses 0.04 ms in duration delivered at a frequency of 3 Hz)with two surface electrodes (Dantec 13L020) applied on the opposite side of the glans penis. Intensity was gradually added from 0 mA until the subject presented a mild stimulus-synchronous prickle sensation of glans and the critical value was recorded.Then it was decreased until the subject just couldn't sense the stimulation.The process was repeated for three times and all the critical values were recorded to obtain the mean sensory threshold of glans penis.
A special 14F Foley catheter with two electrodes mounted on its distal surface(an intraurethral catheter electrode) was designed by ourselves (Chinese patent application number:200710116246.5).The distance between the cathode and the balloon was 1 cm,and the distance between the anode and the cathode was 1.5cm to make sure that the two stimulating electrodes could be just located at the surface of prostatic urethra during the performance.A concentric needle electrode(Dantec DCN37) was inserted percutaneously into the bulbocavernosus muscle as the recording electrode.After the sterile catheter was inserted into the bladder as catheterization and pulled outward gently with the balloon inflated by 10ml water,intensity of the electrical rectangular pulses (duaration was 0.2 ms,l Hz) was gradually added from 0 mA until the subject presented a sense of stimulus-synchronous pulsation of the perineal region at the part of the bulbocavernosus(BC) muscle.Then bulbocavernosus reflex could be recorded with the superimposition technique,however the latencies varied greatly.Moreover,the stimulus-synchronous pulsation could be just palpated by fingers while putting at the part of bulbocavernosus muscle.Then the current intensity was decreased until the subject just presented absence of the pulsation.The process was also repeated for three times and all the critical values of stimulus were recorded to count the average value which was regarded as the sensory threshold of the subject's BCR to stimulation of prostatic urethra.Next,we increased the current intensity until stable BCR with fixed latency was evoked,together with fierce sensation of BC pulsation and higher amplitude.The latency and the critical value of intensity were also recorded.
All findings of the mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR,latencies of BCR and mean sensory thresholds of glans penis in patients with lifelong PE were compared with those of normal potent men.A value out of the reference range was considered abnormal,so we considered the deviation of more than 1.96 SD from the mean controls as the cutoff value to classify the normal and abnormal outcome measures.
Statistical analysis was performed with the Student t test and Pearson correlation analysis by SPSS V16.0(SPSS Inc.,Chicago,IL,USA).A value of P<0.05 was considered statistically significant.
Results
BCR to stimulation of prostatic urethra was successfully detected in all the sixty-two subjects including forty-two patients with lifelong PE and twenty normal controls.While the latencies of BCR were variable at sensory threshold with a lower amplitude,which would become stable at about two times the sensory threshold with an obviously higher amplitude.Besides, the amplitude varied widely even among normal controls under a fixed stimulus which was high enough to evoke stable BCR, probably because of different locations of concentric needle in bulbocavernosus muscle of different subjects.Therefore,it wasn't recorded to be a parameter.
The mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR,latencies of BCR and sensory thresholds of glans penis were 12.38+/-3.71mA(0.2ms in duration,1Hz),23.81+/-5.55mA (0.2ms,1Hz),70.48+/-6.33ms and 11.89+/-2.26mA(0.04ms in duration,3Hz) in the patients with lifelong PE,respectively,and were 18.20+/-2.68mA(0.2ms,1Hz), 34.76+/-4.15mA (0.2ms,1Hz),71.20+/-5.77ms and 14.16+/-1.94mA(0.04ms,3Hz) in the normal potent men,respectively(mean+/-SD). Statistically significant differences were seen regarding the mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR and the mean sensory thresholds of glans penis between the two groups(P< 0.001) indicating that men with lifelong PE had a hyperexcitable BCR to stimulation of prostatic urethra and hyperexcitable sensitivity of glans penis to electrical stimulation than normal potent controls. Whereas,there was no statistically significant differences in the latencies of BCR between the two groups(P>0.05).
The overall results indicated that 29 of 42 patients with lifelong PE (69 per cent) had lower sensory thresholds and 31 patients(74 per cent) had lower thresholds to evoke stable BCR than normal reference values of the control group,while only ten of 42 patients(24%) had hypersensitivity of glans penis compared with the normal controls.
There were positive correlations between sensory thresholds of BCR and thresholds to evoke stable BCR(r=0.946,P<0.001 in patients;r= 0.893, P<0.001 in controls).However,no correlation was found between sensory thresholds of glans penis and sensory thresholds of BCR or thresholds to evoke stable BCR(P>0.05).The results also showed no correlation between age and other outcome measures mentioned above(P>0.05).
In addition,the performance was safe for the subjects without adverse effects,except for temporary urinary frequency which would disappear in few days by drinking more water.
Conclusions
Patients with PPE have hyperexcitable BCR to stimulation of prostatic urethra,which is probably one of the important factors for its etiology. Moreover,the findings may provide new approaches to the treatment of PPE.
Background
Retarded ejaculation(RD) is a rare sexual dysfunction among men.Population studies in the 1990s quoted lower rates ranging from 0 to 3%.A more detailed population based study in the UK of five thousand 16-44 year old men found that 5.3% said that they had experienced an inability to reach orgasm for at least one month in the past year,but only 2.9% had experienced the problem for at least six months in the past year.The Diagnostic and Statistical Manual of Mental Disorders defines retarded ejaculation (RE) as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation, which causes personal distress.Retarded ejaculation can be classified as either a lifelong or acquired, or as global or situational.
Retarded ejaculation is more prevalent as men age.The progressive loss of the fast conducting peripheral sensory axons which begins to be apparent in the third decade of life, and the dermal atrophy,myelin collagen infiltration and pacinian corpuscle degeneration observed in older men, may result in a degree of age-related degenerative penile hypoanesthesia and difficulty in achieving the ejaculatory threshold..
Besides age,physiological factors,congenital and anatomical reasons,pelvic surgery such as radical prostatectomy,transurethral resection of the prostate and bladder neck surgery,pharmacological causes including alpha methyldopa,thiazide diuretics, tricyclic and selective serotonin reuptake inhibitor(SSRI) antidepressants, phenothiazine and alcohol,neurological factors including spinal cord injury and multiple sclerosis(MS),diabetes mellitus and almost any and every psychological problems have been reported to be the etiology of retarded ejaculation, while its precise pathologic mechanisms remains unclear.
Based on the theory that the sense of"ejaculatory inevitability "occurs in response to distention of the posterior urethra and finally results in pulsatile contractions of periurethral musculature which propel the seminal fluid through the urethra,we designed this experiment to study the relationship between bulbocavernosus reflex (BCR) to stimulation of prostatic urethra and retarded ejaculation, which had never been studied before. Also, sensitivity of glans penis to electrical stimulation was recorded.
Objective
In our study the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and retarded ejaculation was studied.
Methods
From September 2007 to March 2009,five patients complaining of retarded ejaculation from our out-patient department of urology and twenty normal potent volunteers (mean age 30.8years,range from 23 to 38,mean height 171.7cm) from labour market were involved in this prospective,case-control study which had been approved by the local ethics committee and all the subjects provided informed consent. All the five patients complaining of retarded ejaculation, mean average estimated IELT(intravaginal ejaculation latency time) more than half an hour from the first intercourse and adverse consequences to the patient and his partner were classified as the RE group and all the normal potent men who presented satisfactory sexual intercourse and good control over ejaculation with the average estimated IELT more than 4 minutes were classified as the control group.Every subject had marriage history of more than one year. Except for retarded ejaculation,none of the patients complained of any other diseases and all the controls were healthy volunteers. They were all free of genitourinary tract infection,erectile dysfunction, systemic(diabetes, alcoholism, hypertension and so on,as well as continuous drug use of selective serotonin reuptake inhibitors (SSRIs),alpha blockers and phosphodiesterase-5 (PDE-5) inhibitors et al that might affect sexual activities by detailed medical and sexual history and comprehensive examinations such as routine tests of urine and expressed prostatic secretions and IIEF-5(international index of erectile function of five items)questionnaire and so on.Moreover,all the subjects didn't have depressive or anxiety disorder,dysthemia,suicidality,(hypo)manic episode,panic disorder, agoraphobia,social phobia,obsessive-compulsive disorder posttraumatic stress disorder or psychotic disorders excluded by MMPI-II(Minnesota Multiphasic Personality Inventory-Ⅱ).Therefore,comorbidity index wasn't used in our study.Besides, for limitation of some objective reasons,Meares-Stamey test which would be better for assessment of genitourinary tract infection wasn't performed.Hence, it might have mild effect to the enrollment of the subjects.In addition, for the electrical examinations on human beings,only height was highlighted,so we ignored the influence of weight to the outcome measures. And only the subjects'height reported by themselves was recorded in this study.There was no statistically significant differences in age and height between the two groups(P>0.05).
The electrical physiological recordings were performed by using a Medtronic Keypoint Electromyograph(Dantec Medical A/S,Skovlunde,Denmark) and during the course each subject was placed supine in a quiet examining room at 24℃after emptying the bladder.
Sensitivity of the glans penis was detected by electrical stimulation (rectangular pulses 0.04 ms in duration delivered at a frequency of 3 Hz)with two surface electrodes (Dantec 13L020) applied on the opposite side of the glans penis.Intensity was gradually added from 0 mA until the subject presented a mild stimulus-synchronous prickle sensation of glans and the critical value was recorded.Then it was decreased until the subject just couldn't sense the stimulation.The process was repeated for three times and all the critical values were recorded to obtain the mean sensory threshold of glans penis.
A special 14F Foley catheter with two electrodes mounted on its distal surface(an intraurethral catheter electrode) was designed by ourselves (Chinese patent application number:200710116246.5).The distance between the cathode and the balloon was 1 cm,and the distance between the anode and the cathode was 1.5cm to make sure that the two stimulating electrodes could be just located at the surface of prostatic urethra during the performance.A concentric needle electrode(Dantec DCN37) was inserted percutaneously into the bulbocavernosus muscle as the recording electrode.After the sterile catheter was inserted into the bladder as catheterization and pulled outward gently with the balloon inflated by 10ml water,intensity of the electrical rectangular pulses (duaration was 0.2 ms,l Hz) was gradually added from 0 mA until the subject presented a sense of stimulus-synchronous pulsation of the perineal region at the part of the bulbocavernosus(BC) muscle.Then bulbocavernosus reflex could be recorded with the superimposition technique,however the latencies varied greatly.Moreover,the stimulus-synchronous pulsation could be just palpated by fingers while putting at the part of bulbocavernosus muscle.Then the current intensity was decreased until the subject just presented absence of the pulsation.The process was also repeated for three times and all the critical values of stimulus were recorded to count the average value which was regarded as the sensory threshold of the subject's BCR to stimulation of prostatic urethra.Next,we increased the current intensity (no more than 80mA for safety)until stable BCR with fixed latency was evoked,together with fierce sensation of BC pulsation and higher amplitude.The latency and the critical value of intensity were also recorded.
All findings of the mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR,latencies of BCR and mean sensory thresholds of glans penis in patients with lifelong PE were compared with those of normal potent men.A value out of the reference range was considered abnormal,so we considered the deviation of more than 1.96 SD from the mean controls as the cutoff value to classify the normal and abnormal outcome measures.
Results
BCR to stimulation of prostatic urethra was successfully detected in all the sixty-two subjects including five patients with retarded ejaculation and twenty normal controls.In normal potent controls, the latencies of BCR were variable at sensory threshold with a lower amplitude,which would become stable at about two times the sensory threshold with an obviously higher amplitude.Besides, the amplitude varied widely even among normal controls under a fixed stimulus which was high enough to evoke stable BCR, probably because of different locations of concentric needle in bulbocavernosus muscle of different subjects.Therefore,it wasn't recorded to be a parameter.
The mean sensory thresholds of BCR to stimulation of prostatic urethra, thresholds to evoke stable BCR,latencies of BCR and sensory thresholds of glans penis were 18.20+/-2.68mA(0.2ms in duration, 1Hz),34.76+/-4.15mA(0.2ms,1Hz), 71.20+/-5.77ms and 14.16+/-1.94mA(0.04ms in duration,3Hz) in the normal potent men,respectively(mean+/-SD).While in patients no stable BCR was evoked under the stimulation of 80mA(0.2ms in duration, 1Hz)and the sensory thresholds of BCR to stimulation of prostatic urethra were 40.20mA、46.45 mA、60.37 mA、51.96 m and 55.26 mA(0.2ms, 1Hz). The sensory thresholds of glans penis to electrical stimulation were 19.30 mA、15.75 mA、14.82 mA、15.27 mA and 13.63mA, respectively. Statistically significant differences were seen regarding the sensory thresholds of BCR to stimulation of prostatic urethra between the two groups.No statistically differences were seen regarding the sensory thresholds of glans penis between the two groups.
In addition,the performance was safe for the subjects without adverse effects,except for temporary urinary frequency which would disappear in few days by drinking more water.
Conclusions
Patients with retarded ejaculation have hypoexcitable BCR to stimulation of prostatic urethra,which is probably one of the important factors for its etiology.
早泄是最常见的男子性功能障碍性疾病,全球发病率高达9%-31%,主要分为原发性早泄和继发性早泄。其中,原发性早泄的发病率低于继发性早泄,但其具体的发病率尚难以确定。根据国际性医学学会(ISSM)的最新定义,原发性早泄需具备以下特征：阴道内射精潜伏期(IELT)总是或几乎总是小于1分钟；缺乏随意控制射精的能力；导致一些负面的影响,如忧虑、烦恼、沮丧或／和回避性生活等。由于约有10%的原发性早泄患者阴道内射精潜伏期介于1-2分钟之间,因此,射精潜伏期的临界值并非严格规定为1分钟。
尽管越来越多的因素如心理性因素、中枢5-羟色胺能神经介质传递紊乱、基因易感性、阴茎高敏感性、异常的体感诱发电位以及增强的阴茎-大脑皮质反射等被报道与原发性的早泄的病因相关,但由于难以建立原发性早泄的动物模型,相关的研究只能通过临床试验进行,导致研究滞后,发病机制尚不明确,给临床分类诊断及分类治疗带来了困难,难以达到理想的治疗效果。现代医学认为,射精的生理过程是包括泌精过程、射精和性高潮的一系列神经反射过程。在性兴奋期,精液分泌至前列腺部后尿道,此时尿道外括约肌紧张性收缩以防止精液流出,促使后尿道内压增高,产生前列腺尿道压力室效应,而诱发射精紧迫感及尿道周围肌群(球海绵体肌、坐骨海绵体肌等)阵挛性收缩并将精液排出尿道.由此可见,正是前列腺部后尿道压力室效应的形成最终诱发了射精。球海绵体肌又称“射精肌”,是位于球部尿道的一对横纹肌,受会阴神经支配,其收缩可增加尿道内压力,阵挛性收缩将精液排出体外。因此探讨前列腺部后尿道-球海绵体反射在射精功能障碍发病机制中的作用具有重要的意义。基于上述研究及理论基础,我们自主发明了一种尿道电刺激电极,在国内外首次将其应用于原发性早泄发病机制的研究,通过诱发前列腺部后尿道-球海绵体反射,同时结合龟头生物感觉阈值测定探讨原发性早泄的发病机制。
目的
探讨前列腺部后尿道-球海绵体反射(BCR)在原发性早泄(PPE)发病机制中的作用。
方法
自2007年9月至2009年3月,从山东大学齐鲁医院泌尿外科门诊筛选42名符合条件的原发性早泄患者,组成原发性早泄组。从劳务市场招募并筛选20名符合条件的男性健康志愿者,组成健康对照组。该研究获得山东大学齐鲁医院伦理委员会批准。每位入选者均被详细的告知该研究的目的、方法以及操作可能带来的并发症,并在完全自愿的条件下签署知情同意书。
原发性早泄组患者：结婚一年以上或有固定的性伴侣一年以上,年龄24-37岁,平均年龄29.6岁,平均身高172.6cm,检查前一个月内至少4次射精(每两次间隔大于24h),平均计时IELT小于2分钟。自述控制射精的能力差,并因此导致个体忧虑、烦恼、沮丧或／和回避性生活等负面影响。
健康对照组：结婚一年以上或有固定的性伴侣一年以上,年龄23-38岁,平均年龄30.8岁,平均身高171.7cm。均自述有良好的控制射精的能力。因计时IELT难以在志愿者中执行,我们采用自我评估IELT,平均IELT大于4分钟。两组受试者间年龄及身高无统计学差异(P>0.05)。
对所有受试者行国际勃起功能评分问卷-5(IIEF-5),排除阴茎勃起功能障碍。行尿液常规和前列腺液常规排除泌尿系统感染。通过问诊及测血压、血糖排除高血压、糖尿病、酒精依赖症、冠心病等系统性疾病。入选前一个月内未曾服用影响射精功能的药物。通过《明尼苏达多项人格测验-Ⅱ》(MMPI-II)排除明显的精神障碍。
在24摄氏度室温环境下,受试者排尿后,仰卧在检查床上。应用美敦力肌电图诱发电位仪(Medtronic Keypoint,丹麦),分别行龟头敏感度检测以及前列腺部后尿道-球海绵体反射。
龟头敏感度检测：生理盐水清洁龟头表面,将两个表面电极分别置于龟头两侧。将矩形电流脉冲持续时间调整为0.04ms,频率调整为3Hz,从OmA逐渐增加电流强度,直至受试者述可感知龟头部轻微针刺样刺激,记录此时刺激量。然后逐渐减小电流强度,直至受试者述刚刚不能感知上述刺激,再次记录刺激量。重复三次,取平均值,即为该受试者者的龟头生物感觉阈值。
前列腺部后尿道-球海绵体反射：将我们自主发明制作的后尿道电刺激电极应用于诱发前列腺部后尿道-球海绵体反射。正负两个环状电极相距1.5cm,附着在一根14F Foley双腔导尿管远端,其中负极位于正极远端,距离球囊边缘lcm。使用前应用万福金安消毒液浸泡30分钟,并用无菌生理盐水冲洗。应用碘伏对受试者会阴部进行消毒,将后尿道电刺激电极经尿道置入膀胱,球囊内注入l0ml生理盐水,然后轻轻牵拉导尿管,以使两个环状电极位于前列腺后尿道部。球海绵体肌(BC)部应用碘伏皮肤消毒,将一同心圆针电极经皮刺入受试者一侧球海绵体肌。调至H-reflex模式,将矩形电流脉冲持续时间调整为0.2ms,频率调整为1Hz,从OmA开始逐渐增加电流强度,直至受试者述有轻微的球海绵体肌部跳动感,记录此时的刺激量。此时,将手指置于球海绵体肌部触诊可触及轻微的跳动感,同心圆针状电极可记录到肌电活动,但潜伏期极不稳定。将刺激量逐渐减小,直至受试者刚刚不能感知上述跳动感,再次记录此时阈值。重复上述操作三次,求平均值即为前列腺部后尿道-球海绵体反射感觉阈值。逐渐增加前列腺部后尿道电刺激量,直至通过同心圆针电极可记录到具有恒定潜伏期的前列腺部后尿道-球海绵体反射,此时可触诊及强烈的球海绵体肌部跳动,记录此时的刺激阈值,并通过叠加技术测定反射潜伏期。
采用SPSS 16.0统计软件,对两组数据应用正态性检验、成组设计的Student t检验以及Pearson相关性分析。P<0.05为差异有统计学意义。原发性早泄组数据以偏离正常组平均值1.96倍的标准差为异常。
结果
通过电刺激前列腺部后尿道,在所有受试者中均可诱发出球海绵体反射。在感觉阈值的刺激下,这种反射的波幅较低且潜伏期不稳定。随着刺激强度的增大,在大约两倍感觉阈值刺激下,可诱发出具有恒定潜伏期的波形,且具有较高的波幅。然而在同一固定刺激下(足以诱发恒定的球海绵体反射),波幅在不同受试者之间差异较大,且在同一受试者,随同心圆针电极在球海绵体肌的位置不同而变化,因此未作为一项参数进行记录。
在正常对照组,平均后尿道感觉阈值、诱发恒定反射阈值、反射潜伏期以及平均龟头生物感觉阈值分别为18.20+/-2.68mA(0.2ms, 1Hz)、34.76+/-4.15mA (0.2ms, 1Hz)、71.2+/-5.77ms和14.16+/-1.94mA (0.04ms,3Hz).而在原发性早泄组分别为12.38+/-3.71mA (0.2ms, 1Hz),23.81+/-5.55mA (0.2ms, 1Hz), 70.48+/-6.33ms和11.89+/-2.26mA (0.04ms,3Hz)。其中,原发性早泄组后尿道感觉阈值、诱发恒定反射阈值以及龟头生物感觉阈值均小于正常对照组,有统计学差异(P<0.001)。而两组间前列腺部后尿道-球海绵体反射潜伏期无统计学差异(P>0.05)。
数据表明,42名原发性早泄患者中,29名患者前列腺部后尿道-球海绵体反射感觉阈值低于正常参考值,占69%；31名患者诱发恒定反射阈值低于正常参考值,占74%,其中两名患者反射感觉阈值在正常范围。然而,仅有10名患者龟头生物感觉阈值低于正常参考值,占24%,其中有9名同时伴有异常的前列腺部后尿道-球海绵体反射感觉阈值及诱发恒定反射阈值。
相关性分析显示,两组受试者前列腺部后尿道-球海绵体反射感觉阈值及诱发恒定反射阈值均存在显著正相关,其中原发性早泄组,r=0.946,P<0.001,对照组r=0.893,P<0.001.然而,龟头生物感觉阈值与前列腺部后尿道-球海绵体反射感觉阈值以及诱发恒定反射阈值均无相关性(P>0.05)。另外,年龄与上述所有参数未见相关性(P>0.05)。
该研究具有良好的安全性,通过检查后多饮水及短期口服抗生素,所有受试者除一过性尿频外,未出现尿路感染以及尿道狭窄等其他并发症。
结论
原发性早泄患者存在高兴奋性的前列腺部后尿道-球海绵体反射,这可能在原发性早泄的发病机制具有重要的作用,同时也为探讨其他有效的治疗方法提供了新的途径。
研究背景
射精迟缓是一种相对少见的男性射精功能功能障碍。上世纪90年代的的人群调查显示其发病率介于0至3%之间。一项针对年龄16至44岁英国男性的研究结果显示,在5000名被调查者中有5.3%的男性在过去的一年中至少有一个月的时间存在射精迟缓或不射精,而仅有2.9%的男性在过去的一年中至少有6个月存在射精迟缓或不射精。精神疾病诊断与统计手册(DSM)将射精迟缓定义为：在足够的性刺激下,男性出现持续或反复的性高潮延迟或缺失,从而给个体带来忧虑的射精功能障碍。射精迟缓分为原发性和继发性,频发性或偶发性。
射精迟缓随男性年龄的增长,发病率随之增加。在男性的二十至三十岁期间,外周快速传导感觉神经元的进展性丧失变的日趋明显。同时,年长男性出现的表皮萎缩、髓鞘胶原的浸润和环形小体的变性,可能导致一定程度的年龄相关的阴茎退化性低麻醉状态,从而难以达到射精所需的阈值。
除年龄外,研究表明生理因素、先天性和解剖原因、,骨盆区手术包括根治性前列腺切除术、经尿道前列腺电切术和膀胱颈部手术等、药物性因素如左旋多巴、噻嗪类利尿剂、5-羟色胺再摄取抑制剂和三环类抗抑郁药、吩噻嗪和酒精等、脊髓损伤和多发性硬化(MS)等神经性因素、糖尿病和几乎所有的心理问题都可能导致射精迟缓。但其具体的发病机制却并不明确。现代医学认为,射精的生理过程是包括泌精过程、射精和性高潮的一系列神经反射过程。在性兴奋期,精液分泌至前列腺部后尿道,此时尿道外括约肌紧张性收缩以防止精液流出,促使后尿道内压增高,产生前列腺尿道压力室效应,而诱发射精紧迫感及尿道周围肌群(球海绵体肌、坐骨海绵体肌等)阵挛性收缩并将精液排出尿道.由此可见,正是前列腺部后尿道压力室效应的形成最终诱发了射精。球海绵体肌又称“射精肌”,是位于球部尿道的一对横纹肌,受会阴神经支配,其收缩可增加尿道内压力,阵挛性收缩将精液排出体外。因此探讨前列腺部后尿道-球海绵体反射在射精功能障碍发病机制中的作用具有重要的意义。基于上述研究及理论基础,我们自主发明了一种尿道电刺激电极,在国内外首次将其应用于射精迟缓发病机制的研究,通过诱发前列腺部后尿道-球海绵体反射,同时结合龟头生物感觉阈值测定探讨射精迟缓的发病机制。
目的
探讨前列腺部后尿道-球海绵体反射(BCR)在射精迟缓(RE)发病机制中的作用。
方法
自2007年9月至2009年3月,从山东大学齐鲁医院泌尿外科门诊筛选5名符合条件的射精迟缓患者,组成射精迟缓组。从劳务市场招募并筛选20名符合条件的男性健康志愿者,组成健康对照组。该研究获得山东大学齐鲁医院伦理委员会批准。每位入选者均被详细的告知该研究的目的、方法以及操作可能带来的并发症,并在完全自愿的条件下签署知情同意书。
射精迟缓组患者：结婚一年以上或有固定的性伴侣一年以上,年龄26～32岁,平均年龄28.8岁,平均身高172.5cm,在过去一年内经常出现射精迟缓,甚至不射精,平均IELT大于30分钟,并因此导致患者本人或其性伴侣、烦恼、沮丧或／和回避性生活等负面影响,并主动寻求治疗。
健康对照组：结婚一年以上或有固定的性伴侣一年以上,年龄23～38岁,平均年龄30.8岁,平均身高171.7cm。均自述有良好的控制射精的能力和满意的性生活。平均IELT大于4分钟。两组受试者间年龄及身高无统计学差异(P>0.05)。
对所有受试者行国际勃起功能评分问卷-5(IIEF-5),排除阴茎勃起功能障碍。行尿液常规和前列腺液常规排除泌尿系统感染。通过问诊及测血压、血糖排除高血压、糖尿病、酒精依赖症、冠心病等系统性疾病。入选前一个月内未曾服用影响射精功能的药物。通过《明尼苏达多项人格测验-Ⅱ》(MMPI-II)排除明显的精神障碍。
在24摄氏度室温环境下,受试者排尿后,仰卧在检查床上。应用美敦力肌电图诱发电位仪(Medtronic Keypoint,丹麦),分别行龟头敏感度检测以及前列腺部后尿道-球海绵体反射。
龟头敏感度检测：生理盐水清洁龟头表面,将两个表面电极(丹迪13L020,丹麦)分别置于龟头两侧。将矩形电流脉冲持续时间调整为0.04ms,频率调整为3Hz,从OmA逐渐增加电流强度,直至受试者述可感知龟头部轻微针刺样刺激,记录此时刺激量。然后逐渐减小电流强度,直至受试者述刚刚不能感知上述刺激,再次记录刺激量。重复三次,取平均值,即为该受试者的龟头生物感觉阈值。
前列腺部后尿道-球海绵体反射：将我们自主发明制作的后尿道电刺激电极应用于诱发前列腺部后尿道-球海绵体反射。正负两个环状电极相距1.5cm,附着在一根14F Foley双腔导尿管远端,其中负极位于正极远端,距离球囊边缘1cm。使用前应用万福金安消毒液浸泡30分钟,并用无菌生理盐水冲洗。应用碘伏对受试者会阴部进行消毒,将后尿道电刺激电极经尿道置入膀胱,球囊内注入10ml生理盐水,然后轻轻牵拉导尿管,以使两个环状电极位于前列腺后尿道部。球海绵体肌(BC)部应用碘伏皮肤消毒,将一同心圆针电极(丹迪DCN37,丹麦)经皮刺入受试者一侧球海绵体肌。调至H-reflex模式,将矩形电流脉冲持续时间调整为0.2ms,频率调整为1Hz,从OmA开始逐渐增加电流强度,直至受试者述有轻微的球海绵体肌部跳动感,记录此时的刺激量。此时,将手指置于球海绵体肌部触诊可触及轻微的跳动感,同心圆针状电极可记录到肌电活动,但潜伏期极不稳定。将刺激量逐渐减小,直至受试者刚刚不能感知上述跳动感,再次记录此时阈值。重复上述操作三次,求平均值即为前列腺部后尿道-球海绵体反射感觉阈值。逐渐增加前列腺部后尿道电刺激量(为保证受试者安全,最高电刺激量定为80mA),直至通过同心圆针电极可记录到具有恒定潜伏期的前列腺部后尿道-球海绵体反射,此时可触诊及强烈的球海绵体肌部跳动,记录此时的刺激阈值,并通过叠加技术测定反射潜伏期。射精迟缓组数据以偏离正常对照组平均值1.96倍的标准差为异常。
结果
通过电刺激前列腺部后尿道,在所有受试者中均可诱发出球海绵体反射。在正常对照组,在感觉阈值的刺激下,这种反射的波幅较低且潜伏期不稳定,随着刺激强度的增大,在大约两倍感觉阈值刺激下,可诱发出具有恒定潜伏期的波形,且具有较高的波幅。然而在同一固定刺激下(足以诱发恒定的球海绵体反射),波幅在不同受试者之间差异较大,且在同一受试者,随同心圆针电极在球海绵体肌的位置不同而变化,因此未作为一项参数进行记录。在射精迟缓组,在80mA(0.2ms, 1Hz)电刺激下(最大安全电刺激量),均未诱发出恒定的前列腺部后尿道-球海绵体反射。
正常对照组后尿道感觉阈值、诱发恒定反射阈值、反射潜伏期以及龟头生物感觉阈值分别为18.20+/-2.68mA (0.2ms, 1Hz)、34.76+/-4.15mA (0.2ms, 1Hz)、71.20+/-5.77ms和14.16+/-1.94mA (0.04ms,3Hz)。射精迟缓组后尿道感觉阈值分别为40.20mA、46.45 mA、60.37 mA、51.96 mA和55.26 mA (0.2ms, 1Hz),对应的龟头生物感觉阈值分别为19.30 mA、15.75 mA、14.82 mA、15.27 mA以及13.63mA。射精迟缓组后尿道感觉阈值明显高于正常对照组,龟头生物感觉阈值与对照组无明显差别。
该研究具有良好的安全性,通过检查后多饮水及短期口服抗生素,所有受试者除一过性尿频外,未出现尿路感染以及尿道狭窄等其他并发症。
结论
射精迟缓患者存在低兴奋性的前列腺部后尿道-球海绵体反射,这可能在射精迟缓的发病机制中具有重要的作用。
Background
Premature ejaculation (PE) is the most common sexual dysfunction all over the world with a prevalence ranging from 9% to 31% of the general male population.It may be mainly divided into lifelong PE and acquired PE.While the incidence of lifelong PE is believed to be much smaller despite it hasn't been reliably determined. According to the ISSM(the International Society for Sexual Medicine) definition of lifelong PE,it is characterized by ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration,the inability to delay ejaculation on all or nearly all vaginal penetrations,and with negative personal consequences,such as distress,bother,frustration,and/or the avoidance of sexual intimacy. While the 1-minute IELT cutoff point should not be applied in the most absolute sense,as about 10% of men seeking treatment for lifelong PE have IELTs of 1-2 minutes.
More and more factors such as psychological factors,disturbance of central serotoninergic neurotransmission,genetic vulnerability,penile hypersensitivity, abnormal somatosensory evoked potentials, greater cortical penile representation and so on have been reported to be related to the etiology of lifelong PE.While because it is very hard to establish the animal model of lifelong PE,the related research could only be carried by clinical trials,which results in the unclear mechanism,and makes diagnosis and therapy difficult. Based on the theory that the sense of "ejaculatory inevitability" occurs in response to distention of the posterior urethra and finally results in pulsatile contractions of periurethral musculature which propel the seminal fluid through the urethra,we invented and designed a special transurethral electrode to study the relationship between bulbocavernosus reflex (BCR) to stimulation of prostatic urethra and lifelong PE, which had never been studied before. Also, sensitivity of glans penis to electrical stimulation was recorded.
Objective
In our study the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and primary premature ejaculation was studied.
Methods
From September 2007 to March 2009,forty-two patients(mean age 29.6 years,range from 24 to 37,mean height 172.6cm)complaining of lifelong PE from our out-patient department of urology and twenty normal potent volunteers (mean age 30.8years,range from 23 to 38,mean height 171.7cm) from labour market were involved in this prospective,case-control study which had been approved by the local ethics committee and all the subjects provided informed consent. All the forty-two patients complaining of unsatisfactory intercourse with poor control over ejaculation and average stopwatch IELT(intravaginal ejaculation latency time) within 2 minutes (38 of them within 1 minute)were classified as the lifelong PE group and all the normal potent men who presented satisfactory sexual intercourse and good control over ejaculation with the average estimated IELT more than 4 minutes were classified as the control group,for the stopwatch IELT was hard to be obtained in the healthy controls. Baseline stopwatch IELT was measured for the 4-week baseline period during which patients were asked to have at least four intercourses at least 24 hours apart.Every subject had marriage history of more than one year. Except for lifelong PE,none of the patients complained of any other diseases and all the controls were healthy volunteers. They were all free of genitourinary tract infection,erectile dysfunction, systemic(diabetes, alcoholism, hypertension and so on,as well as continuous drug use of selective serotonin reuptake inhibitors (SSRIs),alpha blockers and phosphodiesterase-5 (PDE-5) inhibitors et al that might affect sexual activities by detailed medical and sexual history and comprehensive examinations such as routine tests of urine and expressed prostatic secretions and IIEF-5(international index of erectile function of five items)questionaire and so on.Moreover,all the subjects didn't have depressive or anxiety disorder,dysthemia,suicidality,(hypo)manic episode,panic disorder,agoraphobia,social phobia,obsessive-compulsive disorder posttraumatic stress disorder or psychotic disorders excluded by MMPI-II(Minnesota Multiphasic Personality Inventory-Ⅱ).Therefore,comorbidity index wasn't used in our study.Besides, for limitation of some objective reasons,Meares-Stamey test which would be better for assessment of genitourinary tract infection wasn't performed.Hence, it might have mild effect to the enrollment of the subjects.In addition, for the electrical examinations on human beings,only height was highlighted,so we ignored the influence of weight to the outcome measures. And only the subjects'height reported by themselves was recorded in this study.There was no statistically significant differences in age and height between the two groups(P>0.05).
The electrical physiological recordings were performed by using a Medtronic Keypoint Electromyograph(Dantec Medical A/S,Skovlunde,Denmark) and during the course each subject was placed supine in a quiet examining room at 24℃after emptying the bladder.
Sensitivity of the glans penis was detected by electrical stimulation (rectangular pulses 0.04 ms in duration delivered at a frequency of 3 Hz)with two surface electrodes (Dantec 13L020) applied on the opposite side of the glans penis. Intensity was gradually added from 0 mA until the subject presented a mild stimulus-synchronous prickle sensation of glans and the critical value was recorded.Then it was decreased until the subject just couldn't sense the stimulation.The process was repeated for three times and all the critical values were recorded to obtain the mean sensory threshold of glans penis.
A special 14F Foley catheter with two electrodes mounted on its distal surface(an intraurethral catheter electrode) was designed by ourselves (Chinese patent application number:200710116246.5).The distance between the cathode and the balloon was 1 cm,and the distance between the anode and the cathode was 1.5cm to make sure that the two stimulating electrodes could be just located at the surface of prostatic urethra during the performance.A concentric needle electrode(Dantec DCN37) was inserted percutaneously into the bulbocavernosus muscle as the recording electrode.After the sterile catheter was inserted into the bladder as catheterization and pulled outward gently with the balloon inflated by 10ml water,intensity of the electrical rectangular pulses (duaration was 0.2 ms,l Hz) was gradually added from 0 mA until the subject presented a sense of stimulus-synchronous pulsation of the perineal region at the part of the bulbocavernosus(BC) muscle.Then bulbocavernosus reflex could be recorded with the superimposition technique,however the latencies varied greatly.Moreover,the stimulus-synchronous pulsation could be just palpated by fingers while putting at the part of bulbocavernosus muscle.Then the current intensity was decreased until the subject just presented absence of the pulsation.The process was also repeated for three times and all the critical values of stimulus were recorded to count the average value which was regarded as the sensory threshold of the subject's BCR to stimulation of prostatic urethra.Next,we increased the current intensity until stable BCR with fixed latency was evoked,together with fierce sensation of BC pulsation and higher amplitude.The latency and the critical value of intensity were also recorded.
All findings of the mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR,latencies of BCR and mean sensory thresholds of glans penis in patients with lifelong PE were compared with those of normal potent men.A value out of the reference range was considered abnormal,so we considered the deviation of more than 1.96 SD from the mean controls as the cutoff value to classify the normal and abnormal outcome measures.
Statistical analysis was performed with the Student t test and Pearson correlation analysis by SPSS V16.0(SPSS Inc.,Chicago,IL,USA).A value of P<0.05 was considered statistically significant.
Results
BCR to stimulation of prostatic urethra was successfully detected in all the sixty-two subjects including forty-two patients with lifelong PE and twenty normal controls.While the latencies of BCR were variable at sensory threshold with a lower amplitude,which would become stable at about two times the sensory threshold with an obviously higher amplitude.Besides, the amplitude varied widely even among normal controls under a fixed stimulus which was high enough to evoke stable BCR, probably because of different locations of concentric needle in bulbocavernosus muscle of different subjects.Therefore,it wasn't recorded to be a parameter.
The mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR,latencies of BCR and sensory thresholds of glans penis were 12.38+/-3.71mA(0.2ms in duration,1Hz),23.81+/-5.55mA (0.2ms,1Hz),70.48+/-6.33ms and 11.89+/-2.26mA(0.04ms in duration,3Hz) in the patients with lifelong PE,respectively,and were 18.20+/-2.68mA(0.2ms,1Hz), 34.76+/-4.15mA (0.2ms,1Hz),71.20+/-5.77ms and 14.16+/-1.94mA(0.04ms,3Hz) in the normal potent men,respectively(mean+/-SD). Statistically significant differences were seen regarding the mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR and the mean sensory thresholds of glans penis between the two groups(P< 0.001) indicating that men with lifelong PE had a hyperexcitable BCR to stimulation of prostatic urethra and hyperexcitable sensitivity of glans penis to electrical stimulation than normal potent controls. Whereas,there was no statistically significant differences in the latencies of BCR between the two groups(P>0.05).
The overall results indicated that 29 of 42 patients with lifelong PE (69 per cent) had lower sensory thresholds and 31 patients(74 per cent) had lower thresholds to evoke stable BCR than normal reference values of the control group,while only ten of 42 patients(24%) had hypersensitivity of glans penis compared with the normal controls.
There were positive correlations between sensory thresholds of BCR and thresholds to evoke stable BCR(r=0.946,P<0.001 in patients;r= 0.893, P<0.001 in controls).However,no correlation was found between sensory thresholds of glans penis and sensory thresholds of BCR or thresholds to evoke stable BCR(P>0.05).The results also showed no correlation between age and other outcome measures mentioned above(P>0.05).
In addition,the performance was safe for the subjects without adverse effects,except for temporary urinary frequency which would disappear in few days by drinking more water.
Conclusions
Patients with PPE have hyperexcitable BCR to stimulation of prostatic urethra,which is probably one of the important factors for its etiology. Moreover,the findings may provide new approaches to the treatment of PPE.
Background
Retarded ejaculation(RD) is a rare sexual dysfunction among men.Population studies in the 1990s quoted lower rates ranging from 0 to 3%.A more detailed population based study in the UK of five thousand 16-44 year old men found that 5.3% said that they had experienced an inability to reach orgasm for at least one month in the past year,but only 2.9% had experienced the problem for at least six months in the past year.The Diagnostic and Statistical Manual of Mental Disorders defines retarded ejaculation (RE) as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation, which causes personal distress.Retarded ejaculation can be classified as either a lifelong or acquired, or as global or situational.
Retarded ejaculation is more prevalent as men age.The progressive loss of the fast conducting peripheral sensory axons which begins to be apparent in the third decade of life, and the dermal atrophy,myelin collagen infiltration and pacinian corpuscle degeneration observed in older men, may result in a degree of age-related degenerative penile hypoanesthesia and difficulty in achieving the ejaculatory threshold..
Besides age,physiological factors,congenital and anatomical reasons,pelvic surgery such as radical prostatectomy,transurethral resection of the prostate and bladder neck surgery,pharmacological causes including alpha methyldopa,thiazide diuretics, tricyclic and selective serotonin reuptake inhibitor(SSRI) antidepressants, phenothiazine and alcohol,neurological factors including spinal cord injury and multiple sclerosis(MS),diabetes mellitus and almost any and every psychological problems have been reported to be the etiology of retarded ejaculation, while its precise pathologic mechanisms remains unclear.
Based on the theory that the sense of"ejaculatory inevitability "occurs in response to distention of the posterior urethra and finally results in pulsatile contractions of periurethral musculature which propel the seminal fluid through the urethra,we designed this experiment to study the relationship between bulbocavernosus reflex (BCR) to stimulation of prostatic urethra and retarded ejaculation, which had never been studied before. Also, sensitivity of glans penis to electrical stimulation was recorded.
Objective
In our study the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and retarded ejaculation was studied.
Methods
From September 2007 to March 2009,five patients complaining of retarded ejaculation from our out-patient department of urology and twenty normal potent volunteers (mean age 30.8years,range from 23 to 38,mean height 171.7cm) from labour market were involved in this prospective,case-control study which had been approved by the local ethics committee and all the subjects provided informed consent. All the five patients complaining of retarded ejaculation, mean average estimated IELT(intravaginal ejaculation latency time) more than half an hour from the first intercourse and adverse consequences to the patient and his partner were classified as the RE group and all the normal potent men who presented satisfactory sexual intercourse and good control over ejaculation with the average estimated IELT more than 4 minutes were classified as the control group.Every subject had marriage history of more than one year. Except for retarded ejaculation,none of the patients complained of any other diseases and all the controls were healthy volunteers. They were all free of genitourinary tract infection,erectile dysfunction, systemic(diabetes, alcoholism, hypertension and so on,as well as continuous drug use of selective serotonin reuptake inhibitors (SSRIs),alpha blockers and phosphodiesterase-5 (PDE-5) inhibitors et al that might affect sexual activities by detailed medical and sexual history and comprehensive examinations such as routine tests of urine and expressed prostatic secretions and IIEF-5(international index of erectile function of five items)questionnaire and so on.Moreover,all the subjects didn't have depressive or anxiety disorder,dysthemia,suicidality,(hypo)manic episode,panic disorder, agoraphobia,social phobia,obsessive-compulsive disorder posttraumatic stress disorder or psychotic disorders excluded by MMPI-II(Minnesota Multiphasic Personality Inventory-Ⅱ).Therefore,comorbidity index wasn't used in our study.Besides, for limitation of some objective reasons,Meares-Stamey test which would be better for assessment of genitourinary tract infection wasn't performed.Hence, it might have mild effect to the enrollment of the subjects.In addition, for the electrical examinations on human beings,only height was highlighted,so we ignored the influence of weight to the outcome measures. And only the subjects'height reported by themselves was recorded in this study.There was no statistically significant differences in age and height between the two groups(P>0.05).
The electrical physiological recordings were performed by using a Medtronic Keypoint Electromyograph(Dantec Medical A/S,Skovlunde,Denmark) and during the course each subject was placed supine in a quiet examining room at 24℃after emptying the bladder.
Sensitivity of the glans penis was detected by electrical stimulation (rectangular pulses 0.04 ms in duration delivered at a frequency of 3 Hz)with two surface electrodes (Dantec 13L020) applied on the opposite side of the glans penis.Intensity was gradually added from 0 mA until the subject presented a mild stimulus-synchronous prickle sensation of glans and the critical value was recorded.Then it was decreased until the subject just couldn't sense the stimulation.The process was repeated for three times and all the critical values were recorded to obtain the mean sensory threshold of glans penis.
A special 14F Foley catheter with two electrodes mounted on its distal surface(an intraurethral catheter electrode) was designed by ourselves (Chinese patent application number:200710116246.5).The distance between the cathode and the balloon was 1 cm,and the distance between the anode and the cathode was 1.5cm to make sure that the two stimulating electrodes could be just located at the surface of prostatic urethra during the performance.A concentric needle electrode(Dantec DCN37) was inserted percutaneously into the bulbocavernosus muscle as the recording electrode.After the sterile catheter was inserted into the bladder as catheterization and pulled outward gently with the balloon inflated by 10ml water,intensity of the electrical rectangular pulses (duaration was 0.2 ms,l Hz) was gradually added from 0 mA until the subject presented a sense of stimulus-synchronous pulsation of the perineal region at the part of the bulbocavernosus(BC) muscle.Then bulbocavernosus reflex could be recorded with the superimposition technique,however the latencies varied greatly.Moreover,the stimulus-synchronous pulsation could be just palpated by fingers while putting at the part of bulbocavernosus muscle.Then the current intensity was decreased until the subject just presented absence of the pulsation.The process was also repeated for three times and all the critical values of stimulus were recorded to count the average value which was regarded as the sensory threshold of the subject's BCR to stimulation of prostatic urethra.Next,we increased the current intensity (no more than 80mA for safety)until stable BCR with fixed latency was evoked,together with fierce sensation of BC pulsation and higher amplitude.The latency and the critical value of intensity were also recorded.
All findings of the mean sensory thresholds of BCR to stimulation of prostatic urethra,thresholds to evoke stable BCR,latencies of BCR and mean sensory thresholds of glans penis in patients with lifelong PE were compared with those of normal potent men.A value out of the reference range was considered abnormal,so we considered the deviation of more than 1.96 SD from the mean controls as the cutoff value to classify the normal and abnormal outcome measures.
Results
BCR to stimulation of prostatic urethra was successfully detected in all the sixty-two subjects including five patients with retarded ejaculation and twenty normal controls.In normal potent controls, the latencies of BCR were variable at sensory threshold with a lower amplitude,which would become stable at about two times the sensory threshold with an obviously higher amplitude.Besides, the amplitude varied widely even among normal controls under a fixed stimulus which was high enough to evoke stable BCR, probably because of different locations of concentric needle in bulbocavernosus muscle of different subjects.Therefore,it wasn't recorded to be a parameter.
The mean sensory thresholds of BCR to stimulation of prostatic urethra, thresholds to evoke stable BCR,latencies of BCR and sensory thresholds of glans penis were 18.20+/-2.68mA(0.2ms in duration, 1Hz),34.76+/-4.15mA(0.2ms,1Hz), 71.20+/-5.77ms and 14.16+/-1.94mA(0.04ms in duration,3Hz) in the normal potent men,respectively(mean+/-SD).While in patients no stable BCR was evoked under the stimulation of 80mA(0.2ms in duration, 1Hz)and the sensory thresholds of BCR to stimulation of prostatic urethra were 40.20mA、46.45 mA、60.37 mA、51.96 m and 55.26 mA(0.2ms, 1Hz). The sensory thresholds of glans penis to electrical stimulation were 19.30 mA、15.75 mA、14.82 mA、15.27 mA and 13.63mA, respectively. Statistically significant differences were seen regarding the sensory thresholds of BCR to stimulation of prostatic urethra between the two groups.No statistically differences were seen regarding the sensory thresholds of glans penis between the two groups.
In addition,the performance was safe for the subjects without adverse effects,except for temporary urinary frequency which would disappear in few days by drinking more water.
Conclusions
Patients with retarded ejaculation have hypoexcitable BCR to stimulation of prostatic urethra,which is probably one of the important factors for its etiology.
引文
1 Giuliano F, Patrick DL, Porst H, La Pera G, Kokoszka A, Merchant S, Rothman M, Gagnon DD,Polverejan E, for the 2004 Study Group. Premature ejaculation:Results from a five-country European observational Study.Eur Urol 2008;53:1048-57.
2 McMahon CG, Althof SE,Waldinger MD, Porst H,Dean J, Sharlip ID, Adaikan PG, Becher E, Broderick GA, Buvat J, Dabees K, Giraldi A, Giuliano F,Hellstrom WJ, Incrocci L, Laan E, Meuleman E,Perelman MA, Rosen RC, Rowland DL, Segraves R.An evidence-based definition of lifelong premature ejaculation:Report of the International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the definition of premature ejaculation.J Sex Med 2008;5:1590-606.
3 Waldinger MD.Premature ejaculation:different pathophysiologies and etiologies determine its treatment.J Sex Marital Ther 2008;34(1):1-13
4 Waldinger MD.Quinn P,Dilleen M,Mundayat R,Schweitzer DH,Boolell MA. Multinational population.survey of intravaginal ejaculation latency time.J Sex Med 2005;2:492-7.
5 Waldinger MD, Berendsen HHG, Blok BFM,Olivier B, Holstege G. Premature ejaculation andserotonergic antidepressants-induced delayed ejaculation:The involvement of the serotonergic system.Behav Brain Res 1998;92:111-8.
6 De Jong TR, Veening JG, Waldinger MD, CoolsAR, Olivier B. Serotonin and the neurobiology of the ejaculatory threshold. Neurosci Biobehav Rev 2006;30:893-907.
7 Giuliano F, Clement P. Serotonin and premature ejaculation:From physiology to patient management.Eur Urol 2006;50:454-66.
8 Giuliano F. Interview with Dr Francois Giuliano (by Christine McKillop):New avenues in the pharmacologicaltreatment of premature ejaculation. Eur Urol 2007;52:1254-7.
9 Waldinger MD, Rietschel M, Nothen MM, Hengeveld.MW, Oliver B. Familial occurrence of primary premature ejaculation. Psychiatr Genet 1998;8:37-40
10 Jern P, Santtila P, Witting K, Alanko K, Harlaar N, Johansson A, von der Pahlen B, Varjonen M, Vikstrom N, Algars M, Sandnabba K. Premature and Delayed Ejaculation:Genetic and Environmental Effects in a Population-Based Sample of Finnish Twins. J Sex Med 2007;4:1739-1749.
11 Janssen PK, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, Waldinger MD. Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation. J Sex Med 2009;6:276-284.
12 Xin ZC, Chung WS, Choi YD,SEONG DH,CHOI YJ,CHOI HK.Penile sensitivity in patients with primary premature ejaculation. J Urol 156:979-981,1996.
13 Rowland DL, Haensel SM, Blom JH, Slob AK.Penile sensitivity in men with premature ejaculation and erectile dysfunction. J Sex Marital Ther 1993; 19:189-97.
14 Paick JS,Jeong H,Park MS. Penile sensitivity in men with premature ejaculation.Int J Impot Res 1998; 10:247-50.
15 Xin ZC,Choi YD,Rha KH,Choi HK.Somatosensory evoked potentials in patients with primary premature ejaculation. J Urol 1997 158 (2):451-5.
16 Colpi GM, Fanciullacci F, Beretta G, Negri L,Zanollo A. Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986;18:583-6.
17 Fanciullacci F,Colpi GM,Beretta G,Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988;20:326-30.
18 Ozcan C,Ozbek E,Soylu A,Yilmaz U,Guzelipek M,Balbay MD.Auditory event-related potentials in patients with premature ejaculation.Urology 2001;58:1025-9.
19 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro-muscular reflexes.Arch Androl 1998 41(2):71-8.
20 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9.
21 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993; 11:89-95.
22 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002; 14:245-250.
23 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul;170(1):126-9.
24 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerations.J Urol 1991 Jul;146(1):118-23.
25 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
26 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
27 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra:histological and immuno-histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
28 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999; 110:412-418.
29 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
30 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
31 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
32 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
33 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
34 Murphy,J.B.and Lipshultz,L.:Abnormalities of ejaculation. Urol. Clin. N.Amer 1987;14:583.
35 Lechtenberg,R.and Ohl,D.A.:Sexual Dysfunction. Neurologic, Urologic, and Gynecologic Aspects.Philadelphia:Lea&Febiger 1994,176pp.
36 Fanciullacci F, Colpi GM, Beretta G, Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988 Jul- Aug;20(4):326-30.
37 Colpi GM, Fanciullacci F, Beretta G,Neqri L,Zanollo A.Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986;18:583-586.
38 Salonia A, Sacca A, Briganti A, Carro UD, Deho F, Zanni G, Rocchini L,Raber M, Guazzoni G, Rigatti P, and Montorsi F. Quantitative sensory testing of peripheral thresholds in patients with lifelong premature ejaculation:A case-controlled study.J Sex Med 2009;6:1755-1762.
39 A.Perretti,A.Catalano,V.Mirone,C.Imbimbo,P.Balbi,A.Palmieri,N.Longo,F.fusco, P.Verze and L Santoro.Neurophysiologic evaluation of central-peripheral sensory and motor pudendal pathways in primary premature ejaculation.Urology 2003;61:623-628.
40 Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy.Eur Urol 1995;28 (2): 126-30.
41 Perelman MA.A new combination treatment for premature ejaculation:a sex therapists's perspective.J Sex Med 2006 Nov;3(6):1004-12.
1 Fugl-Meyer AR,Sjogren Fugl-Meyer K.Sexual disabilities,problems and satisfaction in 18-74 year olds Swedes.Scand J Sexol 1999;3:79-105
2 Linda E,Stephansson JG.The lifetime prevalence of psychosexual dysfunction among55-57 year olds in Iceland.Soc Psychiatry psychiatr Epidemiol 1993;28:91-5
3 Solstad K,Hertoft P.Frequency of sexual problems and sexual dysfunction in middle aged Danish men.Arch Sex Behav 1993;22:51-8
4 Mercer CH,Fenton KA,Johnson AM,et al.Sexual function problems and health seeking behaviour in ditain:probability sample survey.BMJ 2003;327:426-7
5 American Psychiatry Association. Diagnostic and statistical manual of mental disorders. DSM-Ⅳ.4th edition. Washington DC:American Psychiatric Association; 1994
6 Feldman HA, Goldstein I, Hatzichristou DG, et al.Impotence and its medical and psychosocial correlates:Results of the Massachusetts Male Aging Study. J Urol 1994;151:54.
7 Bindley Gs,Gillan P.Men and women who do not have orgasms.Br J Psychiatry 1982;140:351-6
8 Sank LI.Traumatic masturbatory syndrome.J Sex Marital Ther 1998;24:37-42.
9 Lipsith J,McCann D,Goldmeier D.Male psychogenic dysfunction:the role of masturbation.J sex Relat Ther 2003; 18:447-71
10 McMahon CQAbdo C,Incrocci L,et al.Disorders of orgasm and ejaculation in men.J Sex Med 2004;1:58-64
11 Hendry WF.Disorders of Ejaculation:congenital,acquired and functional.Br J Urol 1998;82:331-41
12 Bores E,Comarr AE.Neurologcal Disturbances of sexual function with special reference to 529 patients with spinal cord injury.Urol Surv 1960; 10:191
13 DasGupta R,Fowler CJ.Sexual and urological dysfunction in multiple sclerosis better understanding and improved therapies.Curr Opin Neurol 2002;15:271-8
14 Thomas A,Lopicollo J.Sexual function in persons with diabetes:issues in research,treatment and education.Clin Psychol Rev 1994; 14:1-86
15 Enzlin P,Mathieu C,Van Den Bruel A,Vanderschueren D,Demyttenaere K.Prevalence and predictors of sexual dysfunction in patients with type Ⅰ diabetes.Diab Care 2003;26:409-14
16 Shull GR,Sprenkle DH.Retarded ejaculaton:reconceptualisation and implications for treatment.J Sex Marital Ther 1980;6:234-46
17 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro-muscular reflexes.Arch Androl 1998 41(2):71-8
18 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9
19 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993;11:89-95
20 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002; 14:245-250.
21 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul;170(1):126-9.
22 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerationsJ Urol 1991 Jul; 146(1):118-23.
23 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
24 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
25 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra:histological and immuno- histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
26 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999;110:412-418.
27 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
28 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
29 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
30 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
31 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
1 Giuliano F, Patrick DL, Porst H, La Pera G, Kokoszka A, Merchant S, Rothman M, Gagnon DD,Polverejan E, for the 2004 Study Group. Premature ejaculation:Results from a five-country European observational Study.Eur Urol 2008;53:1048-57.
2 McMahon CG, Althof SE,Waldinger MD, Porst H,Dean J, Sharlip ID, Adaikan PG, Becher E, Broderick GA, Buvat J, Dabees K, Giraldi A, Giuliano F,Hellstrom WJ, Incrocci L, Laan E, Meuleman E,Perelman MA, Rosen RC, Rowland DL, Segraves R.An evidence-based definition of lifelong premature ejaculation:Report of the International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the definition of premature ejaculation.J Sex Med 2008;5:1590-606.
3 Waldinger MD.Premature ejaculation:different pathophysiologies and etiologies determine its treatment.J Sex Marital Ther 2008;34(1):1-13
4 Waldinger MD,Quinn P,Dilleen M,Mundayat R,Schweitzer DH,Boolell MA. Multinational population.survey of intravaginal ejaculation latency time.J Sex Med 2005;2:492-7.
5 Waldinger MD, Berendsen HHG, Blok BFM,Olivier B, Holstege G. Premature ejaculation andserotonergic antidepressants-induced delayed ejaculation:The involvement of the serotonergic system.Behav Brain Res 1998;92:111-8.
6 De Jong TR, Veening JG, Waldinger MD, CoolsAR, Olivier B. Serotonin and the neurobiology of the ejaculatory threshold. Neurosci Biobehav Rev 2006;30:893-907.
7 Giuliano F, Clement P. Serotonin and premature ejaculation:From physiology to patient management.Eur Urol 2006;50:454-66.
8 Giuliano F. Interview with Dr Francois Giuliano (by Christine McKillop):New avenues in the pharmacologicaltreatment of premature ejaculation. Eur Urol 2007;52:1254-7.
9 Waldinger MD, Rietschel M, Nothen MM, Hengeveld.MW, Oliver B. Familial occurrence of primary premature ejaculation. Psychiatr Genet 1998;8:37-40
10 Jern P, Santtila P, Witting K, Alanko K, Harlaar N, Johansson A, von der Pahlen B, Varjonen M, Vikstrom N, Algars M, Sandnabba K. Premature and Delayed Ejaculation:Genetic and Environmental Effects in a Population-Based Sample of Finnish Twins. J Sex Med 2007;4:1739-1749.
11 Janssen PK, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, Waldinger MD.Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation. J Sex Med 2009;6:276-284.
12 Xin ZC, Chung WS, Choi YD,SEONG DH,CHOI YJ,CHOI HK.Penile sensitivity in patients with primary premature ejaculation. J Urol 156:979-981,1996.
13 Rowland DL, Haensel SM, Blom JH, Slob AK.Penile sensitivity in men with premature ejaculation and erectile dysfunction. J Sex Marital Ther 1993; 19:189-97.
14 Paick JS,Jeong H,Park MS. Penile sensitivity in men with premature ejaculation.Int J Impot Res 1998;10:247-50.
15 Xin ZC,Choi YD,Rha KH,Choi HK.Somatosensory evoked potentials in patients with primary premature ejaculation. J Urol 1997 158 (2):451-5.
16 Colpi GM, Fanciullacci F, Beretta G, Negri L,Zanollo A. Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986; 18:583-6.
17 Fanciullacci F,Colpi GM,Beretta G,Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988;20:326-30.
18 Ozcan C,Ozbek E,Soylu A,Yilmaz U,Guzelipek M,Balbay MD.Auditory event-related potentials in patients with premature ejaculation.Urology 2001;58:1025-9.
19 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro- muscular reflexes.Arch Androl 1998 41(2):71-8.
20 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9.
21 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993;11:89-95.
22 Yuan YM, Xin ZC, Jiang H, Guo YJ, Liu WJ, Tian L, Zhu JC. Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation. Asian J Androl 2004;6:121-6.
23 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002; 14:245-250.
24 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul; 170(1):126-9.
25 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerations J Urol 1991 Jul;146(1):118-23.
26 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
27 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
28 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra.histological and immuno-histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
29 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999;110:412-418.
30 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
31 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
32 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
33 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
34 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
35 Murphy,J.B.and Lipshultz,L.:Abnormalities of ejaculation. Urol. Clin. N.Amer 1987;14:583.
36 Lechtenberg,R.and Ohl,D.A.:Sexual Dysfunction. Neurologic, Urologic, and Gynecologic Aspects.Philadelphia:Lea&Febiger 1994,176pp.
37 Fanciullacci F, Colpi GM, Beretta G, Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988 Jul- Aug;20(4):326-30.
38 Colpi GM, Fanciullacci F, Beretta G,Neqri L,Zanollo A.Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986;18:583-586.
39 Salonia A, Sacca A, Briganti A, Carro UD, Deho F, Zanni G, Rocchini L,Raber M, Guazzoni G, Rigatti P, and Montorsi F. Quantitative sensory testing of peripheral thresholds in patients with lifelong premature ejaculation:A case-controlled study.J Sex Med 2009;6:1755-1762.
40 A.Perretti,A.Catalano,V.Mirone,C.Imbimbo,P.Balbi,A.Palmieri,N.Longo,F.fusco, P. Verze and L Santoro.Neurophysiologic evaluation of central-peripheral sensory and motor pudendal pathways in primary premature ejaculation.Urology 2003;61:623-628.
41 Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy.Eur Urol 1995;28 (2): 126-30.
42 Perelman MA.A new combination treatment for premature ejaculation:a sex therapists's perspective.J Sex Med 2006 Nov;3(6):1004-12.
1 Fugl-Meyer AR,Sjogren Fugl-Meyer K.Sexual disabilities,problems and satisfaction in 18-74 year olds Swedes.Scand J Sexol 1999;3:79-105
2 Linda E,Stephansson JGThe lifetime prevalence of psychosexual dysfunction among55-57 year olds in Iceland.Soc Psychiatry psychiatr Epidemiol 1993;28:91-5
3 Solstad K,Hertoft P.Frequency of sexual problems and sexual dysfunction in middle aged Danish men.Arch Sex Behav 1993;22:51-8
4 Mercer CH,Fenton KA,Johnson AM,et al.Sexual function problems and health seeking behaviour in Britain:probability sample survey.BMJ 2003;327:426-7
5 American Psychiatry Association. Diagnostic and statistical manual of mental disorders. DSM-IV.4th edition. Washington DC:American Psychiatric Association; 1994
6 Feldman HA, Goldstein I, Hatzichristou DG, et al.Impotence and its medical and psychosocial correlates:Results of the Massachusetts Male Aging Study. J Urol 1994;151:54.
7 Bindley Gs,Gillan P.Men and women who do not have orgasms.Br J Psychiatry 1982;140:351-6
8 Sank LI.Traumatic masturbatory syndromeJ Sex Marital Ther 1998;24:37-42.
9 Lipsith J,McCann D,Goldmeier D.Male psychogenic dysfunction:the role of masturbation.J sex Relat Ther 2003;18:447-71
10 McMahon CQ,Abdo C,Incrocci L,et al.Disorders of orgasm and ejaculation in men.J Sex Med 2004;1:58-64
11 Hendry WF.Disorders of Ejaculation:congenital,acquired and functional.Br J Urol 1998;82:331-41
12 Bores E,Comarr AE.Neurologcal Disturbances of sexual function with special reference to 529 patients with spinal cord injury.Urol Surv 1960;10:191
13 DasGupta R,Fowler CJ.Sexual and urological dysfunction in multiple sclerosis better understanding and improved therapies.Curr Opin Neurol 2002;15:271-8
14 Thomas A,Lopicollo J.Sexual function in persons with diabetes:issues in research,treatment and education.Clin Psychol Rev 1994; 14:1-86
15 Enzlin P,Mathieu C,Van Den Bruel A,Vanderschueren D,Demyttenaere K.Prevalence and predictors of sexual dysfunction in patients with type Ⅰ diabetes.Diab Care 2003;26:409-14
16 Shull GR,Sprenkle DH.Retarded ejaculaton:reconceptualisation and implications for treatment.J Sex Marital Ther 1980;6:234-46
17 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro- muscular reflexes.Arch Androl 1998 41(2):71-8
18 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9
19 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993;11:89-95
20 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002;14:245-250.
21 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul; 170(1):126-9.
22 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerations.J Urol 1991 Jul;146(1):118-23.
23 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
24 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
25 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra:histological and immuno-histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
26 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999;110:412-418.
27 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
28 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
29 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
30 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
31 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
1.NIH Consensus Conference:Impotence.NIH Consensus Development Panel on Impotence.JAMA,1993,270:83-90.
2. Harwood PJ, Grotz M, Eardley I, Giannoudis PV.Erectile dysfunction after fracture of the pelvis. J Bone Joint Surg [Br] 2005;87:281-90.
3. EL Rhodenl, C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research (2002) 14,245-250
4.Knoll LD, Abrams JH. Application of nocturnal electrobioimpedance volumetric assessment:a feasibility study in men without erectile dysfunction. Urol. 1999,161 (4):1137-40.
5. Aversa A, Sarteschi LM. The role of penile colorduplex ultrasound for the evaluation of erectile dysfunction. J Sex Med 2007;4:1437-47.
6. Broderick GA, Arger P. Duplex Doppler ultrasonography:Non-invasive assessment of penile anatomy and function. Semin Roentgenol 1993;28:43-6
7. Lue TF, Hricak H, Marich KW, Tanagho EA. Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Radiology 1985;155:777-81
8. Shawn J. Bird, Philip M. Hanno.Bulbocavernosus reflex studies and autonomic testing in the diagnosis of erectile dysfunction Journal of Neurological Sciences 154 (1998) 8-13
9. Chao Feng, Yue-Min Xu, Jian-Jun Yu, Xiao-Fang Fei, Lei Chen. Risk Factors for Erectile Dysfunction in Patients with Urethral Strictures Secondary to Blunt Trauma. J Sex Med 2008;5:2656-2661
10. Sarica Y,Karacan I.Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol.1987 Jul;138(1):55-8
11.Andersson KE, Wagner G.Physiology of penile erection.Physiol Rev, 1995,75:191-236.
12.Malavaud B, Mouzin M, Tricoire JL, Game X,Rischmann P, Sarramon JP, et al. Evaluation of male sexual function after pelvic trauma by the International Index of Erectile Function. Urology 2000;55:842-6.
2 McMahon CG, Althof SE,Waldinger MD, Porst H,Dean J, Sharlip ID, Adaikan PG, Becher E, Broderick GA, Buvat J, Dabees K, Giraldi A, Giuliano F,Hellstrom WJ, Incrocci L, Laan E, Meuleman E,Perelman MA, Rosen RC, Rowland DL, Segraves R.An evidence-based definition of lifelong premature ejaculation:Report of the International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the definition of premature ejaculation.J Sex Med 2008;5:1590-606.
3 Waldinger MD.Premature ejaculation:different pathophysiologies and etiologies determine its treatment.J Sex Marital Ther 2008;34(1):1-13
4 Waldinger MD.Quinn P,Dilleen M,Mundayat R,Schweitzer DH,Boolell MA. Multinational population.survey of intravaginal ejaculation latency time.J Sex Med 2005;2:492-7.
5 Waldinger MD, Berendsen HHG, Blok BFM,Olivier B, Holstege G. Premature ejaculation andserotonergic antidepressants-induced delayed ejaculation:The involvement of the serotonergic system.Behav Brain Res 1998;92:111-8.
6 De Jong TR, Veening JG, Waldinger MD, CoolsAR, Olivier B. Serotonin and the neurobiology of the ejaculatory threshold. Neurosci Biobehav Rev 2006;30:893-907.
7 Giuliano F, Clement P. Serotonin and premature ejaculation:From physiology to patient management.Eur Urol 2006;50:454-66.
8 Giuliano F. Interview with Dr Francois Giuliano (by Christine McKillop):New avenues in the pharmacologicaltreatment of premature ejaculation. Eur Urol 2007;52:1254-7.
9 Waldinger MD, Rietschel M, Nothen MM, Hengeveld.MW, Oliver B. Familial occurrence of primary premature ejaculation. Psychiatr Genet 1998;8:37-40
10 Jern P, Santtila P, Witting K, Alanko K, Harlaar N, Johansson A, von der Pahlen B, Varjonen M, Vikstrom N, Algars M, Sandnabba K. Premature and Delayed Ejaculation:Genetic and Environmental Effects in a Population-Based Sample of Finnish Twins. J Sex Med 2007;4:1739-1749.
11 Janssen PK, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, Waldinger MD. Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation. J Sex Med 2009;6:276-284.
12 Xin ZC, Chung WS, Choi YD,SEONG DH,CHOI YJ,CHOI HK.Penile sensitivity in patients with primary premature ejaculation. J Urol 156:979-981,1996.
13 Rowland DL, Haensel SM, Blom JH, Slob AK.Penile sensitivity in men with premature ejaculation and erectile dysfunction. J Sex Marital Ther 1993; 19:189-97.
14 Paick JS,Jeong H,Park MS. Penile sensitivity in men with premature ejaculation.Int J Impot Res 1998; 10:247-50.
15 Xin ZC,Choi YD,Rha KH,Choi HK.Somatosensory evoked potentials in patients with primary premature ejaculation. J Urol 1997 158 (2):451-5.
16 Colpi GM, Fanciullacci F, Beretta G, Negri L,Zanollo A. Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986;18:583-6.
17 Fanciullacci F,Colpi GM,Beretta G,Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988;20:326-30.
18 Ozcan C,Ozbek E,Soylu A,Yilmaz U,Guzelipek M,Balbay MD.Auditory event-related potentials in patients with premature ejaculation.Urology 2001;58:1025-9.
19 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro-muscular reflexes.Arch Androl 1998 41(2):71-8.
20 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9.
21 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993; 11:89-95.
22 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002; 14:245-250.
23 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul;170(1):126-9.
24 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerations.J Urol 1991 Jul;146(1):118-23.
25 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
26 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
27 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra:histological and immuno-histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
28 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999; 110:412-418.
29 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
30 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
31 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
32 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
33 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
34 Murphy,J.B.and Lipshultz,L.:Abnormalities of ejaculation. Urol. Clin. N.Amer 1987;14:583.
35 Lechtenberg,R.and Ohl,D.A.:Sexual Dysfunction. Neurologic, Urologic, and Gynecologic Aspects.Philadelphia:Lea&Febiger 1994,176pp.
36 Fanciullacci F, Colpi GM, Beretta G, Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988 Jul- Aug;20(4):326-30.
37 Colpi GM, Fanciullacci F, Beretta G,Neqri L,Zanollo A.Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986;18:583-586.
38 Salonia A, Sacca A, Briganti A, Carro UD, Deho F, Zanni G, Rocchini L,Raber M, Guazzoni G, Rigatti P, and Montorsi F. Quantitative sensory testing of peripheral thresholds in patients with lifelong premature ejaculation:A case-controlled study.J Sex Med 2009;6:1755-1762.
39 A.Perretti,A.Catalano,V.Mirone,C.Imbimbo,P.Balbi,A.Palmieri,N.Longo,F.fusco, P.Verze and L Santoro.Neurophysiologic evaluation of central-peripheral sensory and motor pudendal pathways in primary premature ejaculation.Urology 2003;61:623-628.
40 Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy.Eur Urol 1995;28 (2): 126-30.
41 Perelman MA.A new combination treatment for premature ejaculation:a sex therapists's perspective.J Sex Med 2006 Nov;3(6):1004-12.
1 Fugl-Meyer AR,Sjogren Fugl-Meyer K.Sexual disabilities,problems and satisfaction in 18-74 year olds Swedes.Scand J Sexol 1999;3:79-105
2 Linda E,Stephansson JG.The lifetime prevalence of psychosexual dysfunction among55-57 year olds in Iceland.Soc Psychiatry psychiatr Epidemiol 1993;28:91-5
3 Solstad K,Hertoft P.Frequency of sexual problems and sexual dysfunction in middle aged Danish men.Arch Sex Behav 1993;22:51-8
4 Mercer CH,Fenton KA,Johnson AM,et al.Sexual function problems and health seeking behaviour in ditain:probability sample survey.BMJ 2003;327:426-7
5 American Psychiatry Association. Diagnostic and statistical manual of mental disorders. DSM-Ⅳ.4th edition. Washington DC:American Psychiatric Association; 1994
6 Feldman HA, Goldstein I, Hatzichristou DG, et al.Impotence and its medical and psychosocial correlates:Results of the Massachusetts Male Aging Study. J Urol 1994;151:54.
7 Bindley Gs,Gillan P.Men and women who do not have orgasms.Br J Psychiatry 1982;140:351-6
8 Sank LI.Traumatic masturbatory syndrome.J Sex Marital Ther 1998;24:37-42.
9 Lipsith J,McCann D,Goldmeier D.Male psychogenic dysfunction:the role of masturbation.J sex Relat Ther 2003; 18:447-71
10 McMahon CQAbdo C,Incrocci L,et al.Disorders of orgasm and ejaculation in men.J Sex Med 2004;1:58-64
11 Hendry WF.Disorders of Ejaculation:congenital,acquired and functional.Br J Urol 1998;82:331-41
12 Bores E,Comarr AE.Neurologcal Disturbances of sexual function with special reference to 529 patients with spinal cord injury.Urol Surv 1960; 10:191
13 DasGupta R,Fowler CJ.Sexual and urological dysfunction in multiple sclerosis better understanding and improved therapies.Curr Opin Neurol 2002;15:271-8
14 Thomas A,Lopicollo J.Sexual function in persons with diabetes:issues in research,treatment and education.Clin Psychol Rev 1994; 14:1-86
15 Enzlin P,Mathieu C,Van Den Bruel A,Vanderschueren D,Demyttenaere K.Prevalence and predictors of sexual dysfunction in patients with type Ⅰ diabetes.Diab Care 2003;26:409-14
16 Shull GR,Sprenkle DH.Retarded ejaculaton:reconceptualisation and implications for treatment.J Sex Marital Ther 1980;6:234-46
17 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro-muscular reflexes.Arch Androl 1998 41(2):71-8
18 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9
19 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993;11:89-95
20 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002; 14:245-250.
21 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul;170(1):126-9.
22 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerationsJ Urol 1991 Jul; 146(1):118-23.
23 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
24 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
25 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra:histological and immuno- histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
26 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999;110:412-418.
27 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
28 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
29 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
30 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
31 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
1 Giuliano F, Patrick DL, Porst H, La Pera G, Kokoszka A, Merchant S, Rothman M, Gagnon DD,Polverejan E, for the 2004 Study Group. Premature ejaculation:Results from a five-country European observational Study.Eur Urol 2008;53:1048-57.
2 McMahon CG, Althof SE,Waldinger MD, Porst H,Dean J, Sharlip ID, Adaikan PG, Becher E, Broderick GA, Buvat J, Dabees K, Giraldi A, Giuliano F,Hellstrom WJ, Incrocci L, Laan E, Meuleman E,Perelman MA, Rosen RC, Rowland DL, Segraves R.An evidence-based definition of lifelong premature ejaculation:Report of the International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the definition of premature ejaculation.J Sex Med 2008;5:1590-606.
3 Waldinger MD.Premature ejaculation:different pathophysiologies and etiologies determine its treatment.J Sex Marital Ther 2008;34(1):1-13
4 Waldinger MD,Quinn P,Dilleen M,Mundayat R,Schweitzer DH,Boolell MA. Multinational population.survey of intravaginal ejaculation latency time.J Sex Med 2005;2:492-7.
5 Waldinger MD, Berendsen HHG, Blok BFM,Olivier B, Holstege G. Premature ejaculation andserotonergic antidepressants-induced delayed ejaculation:The involvement of the serotonergic system.Behav Brain Res 1998;92:111-8.
6 De Jong TR, Veening JG, Waldinger MD, CoolsAR, Olivier B. Serotonin and the neurobiology of the ejaculatory threshold. Neurosci Biobehav Rev 2006;30:893-907.
7 Giuliano F, Clement P. Serotonin and premature ejaculation:From physiology to patient management.Eur Urol 2006;50:454-66.
8 Giuliano F. Interview with Dr Francois Giuliano (by Christine McKillop):New avenues in the pharmacologicaltreatment of premature ejaculation. Eur Urol 2007;52:1254-7.
9 Waldinger MD, Rietschel M, Nothen MM, Hengeveld.MW, Oliver B. Familial occurrence of primary premature ejaculation. Psychiatr Genet 1998;8:37-40
10 Jern P, Santtila P, Witting K, Alanko K, Harlaar N, Johansson A, von der Pahlen B, Varjonen M, Vikstrom N, Algars M, Sandnabba K. Premature and Delayed Ejaculation:Genetic and Environmental Effects in a Population-Based Sample of Finnish Twins. J Sex Med 2007;4:1739-1749.
11 Janssen PK, Bakker SC, Rethelyi J, Zwinderman AH, Touw DJ, Olivier B, Waldinger MD.Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation. J Sex Med 2009;6:276-284.
12 Xin ZC, Chung WS, Choi YD,SEONG DH,CHOI YJ,CHOI HK.Penile sensitivity in patients with primary premature ejaculation. J Urol 156:979-981,1996.
13 Rowland DL, Haensel SM, Blom JH, Slob AK.Penile sensitivity in men with premature ejaculation and erectile dysfunction. J Sex Marital Ther 1993; 19:189-97.
14 Paick JS,Jeong H,Park MS. Penile sensitivity in men with premature ejaculation.Int J Impot Res 1998;10:247-50.
15 Xin ZC,Choi YD,Rha KH,Choi HK.Somatosensory evoked potentials in patients with primary premature ejaculation. J Urol 1997 158 (2):451-5.
16 Colpi GM, Fanciullacci F, Beretta G, Negri L,Zanollo A. Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986; 18:583-6.
17 Fanciullacci F,Colpi GM,Beretta G,Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988;20:326-30.
18 Ozcan C,Ozbek E,Soylu A,Yilmaz U,Guzelipek M,Balbay MD.Auditory event-related potentials in patients with premature ejaculation.Urology 2001;58:1025-9.
19 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro- muscular reflexes.Arch Androl 1998 41(2):71-8.
20 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9.
21 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993;11:89-95.
22 Yuan YM, Xin ZC, Jiang H, Guo YJ, Liu WJ, Tian L, Zhu JC. Sexual function of premature ejaculation patients assayed with Chinese Index of Premature Ejaculation. Asian J Androl 2004;6:121-6.
23 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002; 14:245-250.
24 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul; 170(1):126-9.
25 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerations J Urol 1991 Jul;146(1):118-23.
26 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
27 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
28 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra.histological and immuno-histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
29 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999;110:412-418.
30 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
31 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
32 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
33 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
34 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
35 Murphy,J.B.and Lipshultz,L.:Abnormalities of ejaculation. Urol. Clin. N.Amer 1987;14:583.
36 Lechtenberg,R.and Ohl,D.A.:Sexual Dysfunction. Neurologic, Urologic, and Gynecologic Aspects.Philadelphia:Lea&Febiger 1994,176pp.
37 Fanciullacci F, Colpi GM, Beretta G, Zanollo A.Cortical evoked potentials in subjects with true premature ejaculation.Andrologia 1988 Jul- Aug;20(4):326-30.
38 Colpi GM, Fanciullacci F, Beretta G,Neqri L,Zanollo A.Evoked sacral potentials in subjects with true premature ejaculation.Andrologia 1986;18:583-586.
39 Salonia A, Sacca A, Briganti A, Carro UD, Deho F, Zanni G, Rocchini L,Raber M, Guazzoni G, Rigatti P, and Montorsi F. Quantitative sensory testing of peripheral thresholds in patients with lifelong premature ejaculation:A case-controlled study.J Sex Med 2009;6:1755-1762.
40 A.Perretti,A.Catalano,V.Mirone,C.Imbimbo,P.Balbi,A.Palmieri,N.Longo,F.fusco, P. Verze and L Santoro.Neurophysiologic evaluation of central-peripheral sensory and motor pudendal pathways in primary premature ejaculation.Urology 2003;61:623-628.
41 Cavallini G. Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy.Eur Urol 1995;28 (2): 126-30.
42 Perelman MA.A new combination treatment for premature ejaculation:a sex therapists's perspective.J Sex Med 2006 Nov;3(6):1004-12.
1 Fugl-Meyer AR,Sjogren Fugl-Meyer K.Sexual disabilities,problems and satisfaction in 18-74 year olds Swedes.Scand J Sexol 1999;3:79-105
2 Linda E,Stephansson JGThe lifetime prevalence of psychosexual dysfunction among55-57 year olds in Iceland.Soc Psychiatry psychiatr Epidemiol 1993;28:91-5
3 Solstad K,Hertoft P.Frequency of sexual problems and sexual dysfunction in middle aged Danish men.Arch Sex Behav 1993;22:51-8
4 Mercer CH,Fenton KA,Johnson AM,et al.Sexual function problems and health seeking behaviour in Britain:probability sample survey.BMJ 2003;327:426-7
5 American Psychiatry Association. Diagnostic and statistical manual of mental disorders. DSM-IV.4th edition. Washington DC:American Psychiatric Association; 1994
6 Feldman HA, Goldstein I, Hatzichristou DG, et al.Impotence and its medical and psychosocial correlates:Results of the Massachusetts Male Aging Study. J Urol 1994;151:54.
7 Bindley Gs,Gillan P.Men and women who do not have orgasms.Br J Psychiatry 1982;140:351-6
8 Sank LI.Traumatic masturbatory syndromeJ Sex Marital Ther 1998;24:37-42.
9 Lipsith J,McCann D,Goldmeier D.Male psychogenic dysfunction:the role of masturbation.J sex Relat Ther 2003;18:447-71
10 McMahon CQ,Abdo C,Incrocci L,et al.Disorders of orgasm and ejaculation in men.J Sex Med 2004;1:58-64
11 Hendry WF.Disorders of Ejaculation:congenital,acquired and functional.Br J Urol 1998;82:331-41
12 Bores E,Comarr AE.Neurologcal Disturbances of sexual function with special reference to 529 patients with spinal cord injury.Urol Surv 1960;10:191
13 DasGupta R,Fowler CJ.Sexual and urological dysfunction in multiple sclerosis better understanding and improved therapies.Curr Opin Neurol 2002;15:271-8
14 Thomas A,Lopicollo J.Sexual function in persons with diabetes:issues in research,treatment and education.Clin Psychol Rev 1994; 14:1-86
15 Enzlin P,Mathieu C,Van Den Bruel A,Vanderschueren D,Demyttenaere K.Prevalence and predictors of sexual dysfunction in patients with type Ⅰ diabetes.Diab Care 2003;26:409-14
16 Shull GR,Sprenkle DH.Retarded ejaculaton:reconceptualisation and implications for treatment.J Sex Marital Ther 1980;6:234-46
17 Shafic A. The mechanism of ejaculation:the glans-vasal and urethro- muscular reflexes.Arch Androl 1998 41(2):71-8
18 Shenassa B, Hellstrom W. Understanding ejaculatory disorders.Contemp Urol 2001;13:51-9
19 Witt MA,Grantmyre JE. Ejaculatory failure. World J Urol 1993;11:89-95
20 EL Rhodenl,C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research 2002;14:245-250.
21 Gustafson KJ,Creasey GH,Grill WM.A catheter based method to activate urethral sensoty nerve fibers.J Urol.2003 Jul; 170(1):126-9.
22 Ganzer H, Madersbacher H, Rumpl E.Cortical evoked potentials by stimulation of the vesicourethral junction:clinical value and neurophysiological considerations.J Urol 1991 Jul;146(1):118-23.
23 Sarica Y,Karacan I Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol 1987 Jul;138(1):55-8.
24 Shafik.A,EI-sibai.Mechanism of ejection during ejaculation:identification of a urethrocavernosus.reflex.Arch Androl 2000 Jan-Feb;44(1);77-83
25 I. Karam, S. Moudouni, S. Droupy, I. Abd-Alsamad, J. F. Uhl and V. Delmas. The structure and innervation of the male urethra:histological and immuno-histochemical studies with three-dimensional reconstruction J.Anat 2005; 206:395-403.
26 Yang.C, Bradley WE..Somatic innervation of the human bulbocavernosus muscle.Clinical Neurophysiology 1999;110:412-418.
27 Shafik A. Response of the urethral and intracorporeal pressures to cavernosus muscle stimulation:role of the muscles in erection and ejaculation.Urology 1995 July;46(1):85-8.
28 Gerstenberg T, Levin R, Wagner G. Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles.Br J Urol 1990;65:395-402.
29 Dick H, Bradley W, Scott F, Timm G. Pudendal sexual reflexes: electro-physiologic investigations.Urology 1973;3:376-9.
30 Yang C, Bradley WE. Innervation of the human anterior urethra by the dorsal nerve of the penis. Muscle Nerve 1998;21:514-8.
31 Kyung Won, PhD. Chung (2005). Gross Anatomy (Board Review). Hagerstown, MD:Lippincott Williams & Wilkins 2005,268pp.
1.NIH Consensus Conference:Impotence.NIH Consensus Development Panel on Impotence.JAMA,1993,270:83-90.
2. Harwood PJ, Grotz M, Eardley I, Giannoudis PV.Erectile dysfunction after fracture of the pelvis. J Bone Joint Surg [Br] 2005;87:281-90.
3. EL Rhodenl, C Telo¨ken, PR Sogari, CA Vargas Souto.The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction. International Journal of Impotence Research (2002) 14,245-250
4.Knoll LD, Abrams JH. Application of nocturnal electrobioimpedance volumetric assessment:a feasibility study in men without erectile dysfunction. Urol. 1999,161 (4):1137-40.
5. Aversa A, Sarteschi LM. The role of penile colorduplex ultrasound for the evaluation of erectile dysfunction. J Sex Med 2007;4:1437-47.
6. Broderick GA, Arger P. Duplex Doppler ultrasonography:Non-invasive assessment of penile anatomy and function. Semin Roentgenol 1993;28:43-6
7. Lue TF, Hricak H, Marich KW, Tanagho EA. Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler spectrum analysis. Radiology 1985;155:777-81
8. Shawn J. Bird, Philip M. Hanno.Bulbocavernosus reflex studies and autonomic testing in the diagnosis of erectile dysfunction Journal of Neurological Sciences 154 (1998) 8-13
9. Chao Feng, Yue-Min Xu, Jian-Jun Yu, Xiao-Fang Fei, Lei Chen. Risk Factors for Erectile Dysfunction in Patients with Urethral Strictures Secondary to Blunt Trauma. J Sex Med 2008;5:2656-2661
10. Sarica Y,Karacan I.Bulbocavernosus reflex to somatic and visceral nerve stimulation in normal subjects and in diabetics with erectile impotence.J Urol.1987 Jul;138(1):55-8
11.Andersson KE, Wagner G.Physiology of penile erection.Physiol Rev, 1995,75:191-236.
12.Malavaud B, Mouzin M, Tricoire JL, Game X,Rischmann P, Sarramon JP, et al. Evaluation of male sexual function after pelvic trauma by the International Index of Erectile Function. Urology 2000;55:842-6.