| BackgroundPremature 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.ObjectiveIn our study the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and primary premature ejaculation was studied.MethodsFrom 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. ResultsBCR 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.ConclusionsPatients 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. BackgroundRetarded 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.ObjectiveIn our study the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and retarded ejaculation was studied.MethodsFrom 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. ResultsBCR 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.ConclusionsPatients with retarded ejaculation have hypoexcitable BCR to stimulation of prostatic urethra,which is probably one of the important factors for its etiology.
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