The effect of plasma melatonin levels in the treatment of lifelong premature ejaculation with selective serotonin reuptake inhibitors

The aim of our study was to compare melatonin levels of patients with lifelong premature ejaculation (LPE) (n:60) with healthy controls (n:30) and to investigate the changes of melatonin levels in the treatment with dapoxetine and sertraline. Age, body mass index, duration of marriage, weekly intercourse number, International Index of Erectile Function scores, Intravaginal Ejaculation Latency Time (IELT) and melatonin levels were recorded. LPE patients were divided into two treatment groups. The first group was included 30 patients, who received 60 mg dapoxetine for six weeks, twice a week, an hour before intercourse. The second group received 50 mg of sertraline daily, for six weeks. IELT and melatonin measures were repeated after the treatment. IELT (dapoxetine group: 41.22 ± 21.3 s, sertraline group: 48 ± 23.11 s, control group: 195.54 ± 84.14 s; p < .001) and melatonin levels (dapoxetine group: 5.75 ± 2.04 pg/mL, sertraline group: 5.49 ± 2.88 pg/mL, control group: 13.4 ± 12.09 pg/mL; p < .001) of both LPE groups were significantly lower than control group. Following the six-week sertraline (before: 48 ± 23.11 s, after: 101.01 ± 59.55 s; p < .001) and dapoxetine (before: 41.22 ± 21.3 s, after: 97.39 ± 44.1 s; p < .001) treatments, IELT increased. The melatonin levels increased in the sertraline group (before: 5.49 ± 2.88 pg/mL, after: 10.6 ± 7.37 pg/mL; p < .001). Our results indicate that melatonin levels of LPE patients are lower than levels of healthy volunteers. Furthermore, we found a significant increase in melatonin levels following sertraline treatment.     

Oral dapoxetine versus topical lidocaine as on-demand treatment for lifelong premature ejaculation: A randomised controlled trial

This trial aimed to assess the efficacy of on-demand oral dapoxetine versus topical lidocaine treatments for lifelong PE. Cases with lifelong PE were randomised to start treatment by oral dapoxetine 60 mg or topical lidocaine 10% spray. The intravaginal ejaculatory latency time (ILET), validated Arabic Index for PE (AIPE), Sexual Health Inventory for Men (SHIM) and frequency of intercourse/week were recorded at the baseline and after 12 weeks treatment period of the first medication before two weeks washout period and then crossing over to the other one for another 12 weeks. Results showed that both medications significantly increased both IELT and AIPE scores compared with the baseline being significantly better with topical lidocaine (63.44 s, 179.4 s versus 21.87 s, p < .05). Significant decrease of SHIM score was recorded with lidocaine but not with dapoxetine. Global Efficacy Question for the patient's assessment of the effectiveness of drugs showed that lidocaine was described as being effective by 43 cases and ineffective by 12 cases, oral dapoxetine was described as being effective by 16 cases and ineffective by 39 cases. From these accumulated data, it is concluded that topical lidocaine is more effective on-demand therapy for lifelong PE compared with oral dapoxetine.     

Comparison of the clinical efficacy and safety of the on‐demand use of paroxetine,dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation: A randomised placebo‐controlled clinical trial

The aim of the study was to compare the clinical efficacy and safety of the on‐demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation (PE). In a single‐blind placebo‐controlled clinical study, 150 PE patients without erectile dysfunction (ED) were included during the period of March 2015 to May 2016. Patients were randomly divided into five groups (30 patients each). On demand placebo, paroxetine (30 mg), dapoxetine (30 mg), sildenafil citrate (50 mg) and combined dapoxetine (30 mg) with sildenafil citrate (50 mg) were given for patients for 6 weeks in each group respectively. All patients were instructed to record intravaginal ejaculatory latency time (IELT) and evaluated with Premature Ejaculation Diagnostic Tool (PEDT) and the patient satisfaction score before and after treatment. The mean of IELT, satisfaction score and PEDT in all groups was significantly improved after treatment (p value = .001). Combined dapoxetine with sildenafil group had the best values of IELT, satisfaction scores and PEDT in comparison with other treatment groups (p value <.001). The combined dapoxetine with sildenafil therapy could significantly improve PE patients without ED as compared to paroxetine alone or dapoxetine alone or sildenafil alone with tolerated adverse effects.     

帕罗西汀与达帕西汀的对比，治疗早泄的新的选择性5-羟色胺再摄取抑制剂

达帕西汀氢氯化物是一种选择性5-羟色胺再摄取抑制剂,也是第一种被批准可以按需服用治疗早泄的药物。本文目的为研究按需服用达帕西汀（30mg和H60mg）和每日服用帕罗西汀（20mg）对早泄的疗效。研究募集了150名患者进行了长达1个月的研究。患者被分成3组,每组50人。第一组按需服用达帕西汀30mg。第二组按需服用达帕西汀60mg。第三组每日服用帕罗西汀20mg。治疗结束后,我们的结果检测值相对于基准阴道内射精潜伏期（IELT）延长了。与基准IELT相比,帕罗西汀组、30mg达帕西汀组和60mg达帕西汀组的治疗后IELT分别延长了117％（P〈0．01）,117％（P〈0．01）和170％（P〈0．01）。30mg达帕西汀组和帕罗西汀组的IELT增幅相同（P〉0．05）,而60mg达帕西汀组的IELT增幅明显高于30mg达帕西汀组（P〈0．05和帕罗西汀组P〈0．01）。性交前1～3小时服用达帕西汀60mg是针对早泄的非常有效的治疗方法。然而,与当前普遍使用的帕罗西汀相比,达帕西汀30mg疗效并不显著。     

Combination therapy with selective serotonin reuptake inhibitors and phosphodiesterase‐5 inhibitors in the treatment of premature ejaculation

We aimed to evaluate the effectiveness of paroxetine and tadalafil combination in the treatment of premature ejaculation (PE). A total of 150 primary (lifelong)PE patients were randomly distributed into three groups of 50 patients each. Group 1 received 20 mg paroxetine every day for 1 month, Group 2 received 20 mg tadalafil on demand 2 h before intercourse, and Group 3 received paroxetine and tadalafil on demand 2 h before intercourse. Intravaginal ejaculatory latency times (IELT) scores were evaluated at baseline, at the end of the first month of therapy and 1 month after discontinuation of the treatment, while International Index of Erectile Function (IIEF) questionnaire scores were evaluated both prior to and after the treatment. At the end of the first month of therapy, IELT scores were compared with the basal values and statistically significant changes were detected (60.6 ± 30.2–117.3 ± 67.3, 68.5 ± 21.4–110.2 ± 37.3, 71.56 ± 40.23–175.2 ± 60.2)(P < 0.01). IELT scores after discontinuation of treatment were found to be close to the baseline IELT scores (P > 0.05). IIEF scores were evaluated both prior to and after the treatment, and no statistically significant difference was detected (P > 0.05). It is concluded that utilisation of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase‐5 inhibitors (PDE5i) combination before intercourse seems to provide significantly longer ejaculatory latency times as compared with SSRI alone for a long time in patients with PE.     

Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover study

We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0–8 (0 = almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT) was measured. Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg). After a wash-out phase for 1 week, medication was changed in a cross-over design. Initially, all 72 men with PE received behavioural therapy. Twenty-three men were satisfied with treatment and excluded. The remaining 49 men graded their PE as 5.94 ± 1.6 and IELT was 0.59 min and patients were randomised. Four men discontinued the study. Vardenafil improved PE grading: 2.7 ± 2.1 ( P  < 0.01) and IELT increased to 5.01 ± 3.69 ( P  < 0.001). PE grading improved 1.92 ± 1.32, ( P  < 0.01) and IELT 3.12 ± 1.89 ( P  < 0.001) with sertraline. It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE.     

A prospective randomized study to compare pelvic floor rehabilitation and dapoxetine for treatment of lifelong premature ejaculation

Premature ejaculation (PE) is the most common male sexual disorder. We compared pelvic floor muscle rehabilitation to on-demand treatment with the selective serotonin reuptake inhibitor dapoxetine in 40 men with lifelong PE (baseline intra-vaginal ejaculatory latency time (IELT) ≤1 min). Subjects were randomized into the following two treatment groups: (1) PFM rehabilitation or (2) 30 or 60 mg of on-demand dapoxetine. Total treatment time for both groups was 12 weeks, at the end of which, IELT mean values were calculated to compare the effectiveness of the two different therapeutic approaches. At the end of treatment, 11 of the 19 patients (57%) treated with rehabilitation were able to control the ejaculation reflex, with a mean IELT of 126.6 sec (range: 123.6-152.4 sec). In the dapoxetine group, after 12 weeks of therapy, 5 of 8 (62.5%) patients in the 30 mg subgroup and five of seven (72%) in the 60 mg subgroup had an IELT >180 sec (mean: 178.2 and 202.8 sec, respectively). The results obtained in the group treated with pelvic floor rehabilitation are promising, and this treatment represents an important cost reduction if compared to dapoxetine on-demand treatment. The present study confirms the data that are previously available in the literature on the efficacy and safety of the new inhibitor of serotonin reuptake, dapoxetine, as well as proposes and evaluates a new type of physical treatment that may be a viable therapeutic option for treatment of PE.     

Efficacy of sertraline hydrochloride in treatment of premature ejaculation: a placebo-controlled study using a validated questionnaire

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used to treat premature ejaculation. We report a large prospective placebo-controlled crossover study of sertraline in premature ejaculation (PE) using Arabic Index of Premature Ejaculation (AIPE). One hundred and forty-seven men suffering from PE were enrolled in a randomized single-blinded crossover study of sertraline hydrochloride and placebo. Patients were randomized into group 1 (n=77) and group 2 (n=70). Both groups received sertraline and placebo interchangeably for 4 weeks. Overall, 127 (81%) of 157 subjects experienced a significant increase in their AIPE total score after sertraline treatment. Sixty-six (66%) of 100 patients available for follow-up experienced relapse of PE within 6 months after sertraline withdrawal. The active drug was generally well tolerated. Our relatively large study, using a validated questionnaire (AIPE), confirmed the useful effect of sertraline on PE.     

Effect of premature ejaculation desensitisation therapy combined with dapoxetine hydrochloride on the treatment of primary premature ejaculation

To evaluate the overall treatment benefits of premature ejaculation desensitisation therapy combined with 30 mg dapoxetine hydrochloride treatment on patients with primary premature ejaculation (PPE). Ninety‐nine PPE patients were randomly divided into two groups at the ratio of 2:1. Sixty‐six PPE patients received premature ejaculation desensitisation therapy accomplished by Weili Automatic Semen Collection—Penis Erection Detection and Analysis workstation (WLJY‐2008) combined with 30 mg dapoxetine hydrochloride treatment (DTCD group), and another 33 patients received 30 mg dapoxetine hydrochloride‐only treatment (DO group). Intravaginal ejaculation latency time (IELT) and premature ejaculation profile (PEP) were recorded before and during the treatment, and clinical global impression of change (CGIC) in PPE was recorded at the fourth week and the end of the treatment and the items. In both groups were significantly improved (p < 0.0001) in IELT, PEP and CGIC for premature ejaculation compared with baseline, and DTCD treatment showed a more significant improvement on PPE patients in the items compared with DO treatment (p < 0.05). Thus, premature ejaculation desensitisation combined with dapoxetine therapy may be a better choice for improving premature ejaculation with PPE.     

Impact of physical activity on patient self‐reported outcomes of lifelong premature ejaculation patients: Results of a prospective,randomised, sham‐controlled trial

Previous studies have investigated whether physical activity increases serotonin hormone levels. Serotonin receptor dysfunction is one of the frequently accused factors of premature ejaculation (PE). Nevertheless, no studies up to date have demonstrated that the association between physical activity and premature ejaculation. We aimed to investigate the relationship between physical activity and PE and determine whether moderate physical activity might delay ejaculation time or be an alternative treatment for PE. A total of 105 patients diagnosed with PE were enrolled in this study. Of the patients, 35 were treated with dapoxetine, (30 mg) on demand (Group 1), 35 performed moderate physical activities (Group 2), and 35 performed minimal physical activity (Group 3‐sham). Demographic characteristics, metabolic equivalents (MET), premature ejaculation diagnostic tool (PEDT) and intravaginal ejaculatory latency time (IELT) were recorded. There were no significant differences among three groups in terms of age, BMI, MET, PEDT or IELT before treatment. At the end of the study, there was significant decrease in PEDT scores, and increase in IELT in groups 1 and 2 as compared to Group 3. In conclusion, a moderate physical activity longer than 30 min at least 5 times a week leads to ejaculation delay, and appears as an alternative to dapoxetine on demand for the treatment of PE.     

Dapoxetine for the Treatment of Premature Ejaculation: Results from a Randomized,Double-Blind,Placebo-Controlled Phase 3 Trial in 22 Countries

Background

Dapoxetine is being developed for the on-demand treatment of premature ejaculation (PE). Previous clinical trials have demonstrated its safety and efficacy.

Objective

To evaluate the long-term efficacy and safety of dapoxetine in men with PE.

Design, setting, and participants

This randomized, double-blind, parallel-group, placebo-controlled, phase 3 trial, conducted in 22 countries, enrolled men (N = 1162) ≥18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for ≥6 mo, with an intravaginal ejaculatory latency time (IELT) ≤2 min in ≥75% of intercourse episodes at baseline.

Intervention

Dapoxetine 30 mg or dapoxetine 60 mg or placebo on demand (1–3 h before intercourse) for 24 wk.

Measurements

Stopwatch-measured IELT, Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change, adverse events (AEs).

Results and limitations

The study was completed by 618 men. Mean average IELT increased from 0.9 min at baseline (all groups) to 1.9 min, 3.2 min, and 3.5 min with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively, at study end point; geometric mean IELT increased from 0.7 min at baseline to 1.1 min, 1.8 min, and 2.3 min, respectively, at study end point. All PEP measures and IELTs improved significantly with dapoxetine versus placebo at week 12 and week 24 (p < 0.001 for all). The most common AEs were nausea, dizziness, diarrhea, and headache. AEs led to discontinuation in 1.3%, 3.9%, and 8.2% of subjects with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively. Limitations of this study included the exclusion of men who were not in long-term monogamous relationships.

Conclusions

Dapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population.     

Analysis of association between the 5‐HTTLPR and STin2 polymorphisms in the serotonin‐transporter gene and clinical response to a selective serotonin reuptake inhibitor (sertraline) in patients with premature ejaculation

Study Type – Therapy (cohort)
Level of Evidence 2b

OBJECTIVE

To test the hypothesis that polymorphism within the gene‐linked polymorphic region (5‐HTTLPR) and second intron of SLC6A4 gene (STin2) is associated with selective serotonin‐reuptake inhibitors (SSRIs) response in subjects with premature ejaculation (PE).

PATIENTS AND METHODS

In all, 246 men with PE were recruited in this study. They were asked to take sertraline 50 mg daily for 2 weeks, and thereafter 100 mg daily, for a 12‐week treatment period. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IELT), and International Index of Erectile Function (IIEF). The efficacy of treatment was assessed using responses to IIEF, and geometric mean IELT evaluation. 5‐HTTLPR was genotyped using polymerase chain reaction techniques. A repeated‐measures analysis of variance of geometric mean IELT was done to test a genotype effect on treatment outcome with SSRI (sertraline).

RESULTS

Of 227 participants who completed the study, 175 (77.1%) responded to sertraline (IELT >1 min). Overall the patients had a 3.7‐fold (95% confidence interval, CI, 1.72–5.46) increase of the geometric mean IELT (P = 0.001). The results showed that responses were significantly better for the L_A/L_A genotype of the 5‐HTTLPR polymorphism than for S‐allele carriers (P = 0.001). The STin2 12/12 genotype was found more often in those responding to sertraline than in those not responding (P = 0.001). The probability of patients responding sufficiently to sertraline with an L_A/L_A genotype was highest (odds ratio 4.66, 95% CI, 2.48–6.14).

CONCLUSIONS

These findings indicate that the genotype of 5‐HTT contributes in unique ways to the variation in the outcome of PE treatment with SSRIs.     

Efficacy and safety of daily use of tadalafil in treatment of patients with premature ejaculation: A randomised placebo‐controlled clinical trial

The study aimed to evaluate the efficacy and safety of the once‐daily use of 5 mg tadalafil in the treatment of patients with premature ejaculation (PE). In a single‐blind placebo‐controlled clinical study, it was carried out on 100 patients with PE. All patients were randomised equally divided into two groups (50 patients each). Group 1 was given placebo in the form of oral multivitamin tablet once a day for 6 weeks. Group 2 was given 5 mg tadalafil once a day for 6 weeks. All patients were asked to complete Arabic Index of Premature Ejaculation (AIPE) before and after the treatment. This study showed that there were no statistically significant differences between patients in the placebo and tadalafil groups regarding the mean values of the seven questions and total scores of the AIPE questionnaire before treatment (p value >.05). The mean values of the seven questions and total scores of AIPE questionnaire in the tadalafil group were significantly higher than the placebo group after treatment (p value = .001). This study concluded that once‐daily use of 5 mg tadalafil for 6 weeks was effective and well tolerated in the treatment of patients with PE.     

Treatment of premature ejaculation

Premature ejaculation (PE) is the most common male sexual disorder, and it may have a profound negative impact on a man and his partner's lives. Different organizations and societies have no consensus on the definition and classifications of PE. However, most organizations and societies include in their definitions the intravaginal ejaculation latency time (IELT), the control of ejaculation, and the distress or impact of interpersonal difficulties. Evaluation procedures have been standardized in clinical studies by the development of an objective measurement of IELT (using a stopwatch) and by the introduction of patient-reported outcome (PRO) questionnaires on ejaculation control and sexual satisfaction. The identification of four different patterns of PE—lifelong, acquired, normal variant, and premature-like ejaculatory dysfunction—is critical because of different underlying pathogeneses and consequently different management approaches. The optimal treatment for PE should be individualized, based on a patient's symptoms, expectations, and underlying variant causes. Most lifelong PE patients need pharmacotherapy (possibly in combination with psychosexual counseling) as a first-line treatment because of the underlying neurobiological etiology and the impact of PE on the couple's relationship. The management of acquired PE is etiologically specific and may include pharmacotherapy for erectile function management in men with comorbid erectile dysfunction (ED). Men with natural variable PE complain of early ejaculation in situational or coincidental conditions; the ejaculation is inconsistent and occurs irregularly. Psychoeducation and reassurance are indicated for men with this type of PE. Psychotherapy or sex counseling is the first choice of treatment for men with premature-like ejaculatory dysfunction. All pharmacotherapies such as long-term selective serotonin reuptake inhibitors (SSRIs) or on-demand topical anesthetics are off-label indications, The benefits of pharmacotherapy toward improving ejaculation times should be weighed against their safety profiles. The development of the short-acting selective serotonin reuptake inhibitor (SSRI) dapoxetine hydrochloride (30 mg and 60 mg) for oral on-demand use opened a new era of PE treatment. Other potential pharmacotherapies such as tramadol, lidocaine/prilocaine spray, and phosphodiesterase inhibitors are still under development. Their safety and efficacy profiles should be further evaluated and supported by additional clinical studies.     

Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment �C topical versus systemic

Premature ejaculation (PE) is a common sexual dysfunction affecting 20% to 30% of men worldwide. Definitions of PE vary, but it is typically characterized by short intravaginal ejaculatory latency time (IELT) with concomitant sexual dissatisfaction and distress. PE may be lifelong or acquired, but its etiology remains unclear. Treatment of PE typically involves pharmacotherapy, particularly when lifelong. Although there are numerous reports on the off-label use of selective serotonin reuptake inhibitors (SSRIs) and other compounds, only 2 treatments have been evaluated in randomized controlled phase 3 clinical trials: PSD502 and dapoxetine (SSRI). Both significantly improved IELT and patient-reported outcome domains of ejaculatory control, sexual satisfaction, and distress as measured by the index of premature ejaculation (IPE), compared with placebo. They constitute the focus of this review. Evidence demonstrated that PSD502, dapoxetine and other SSRIs all significantly improve the symptoms of PE. Systemic use of SSRIs presents risks associated with the known pharmacology of this class. PSD502 allows for topical on-demand treatment applied applied immediately before intercourse, and is not associated with systemic adverse events.     

A Novel Treatment of Premature Ejaculation

The investigation of the etiology and treatment of premature ejaculation (PE), a common and significant problem for men and their partners, has been limited by the lack of defined outcomes and differences in clinical trial designs. Currently, no medication has been approved for the treatment for PE worldwide. Recognition of serotonin as a key mediator in ejaculatory signaling has raised interest in the utility of pharmacologic intervention for treating PE. Selective serotonin reuptake inhibitors (SSRIs) have been used off-label for PE, with varied results. However, treatment with currently available SSRIs typically requires chronic dosing that increases drug accumulation and the attendant risk of adverse events. Dapoxetine is an SSRI with a short half-life (1.2 h), developed specifically for the treatment of men with PE. This agent has a unique pharmacokinetic profile characterized by rapid absorption and elimination. Dapoxetine is metabolized by multiple pathways, and no clinically relevant drug–drug interactions have been identified. Furthermore, dapoxetine pharmacokinetics do not appear to be affected by food, age, alcohol, or phosphodiesterase type 5 (PDE5) inhibitors to a relevant degree. In two placebo-controlled phase 3 trials involving >2600 men with PE, dapoxetine 60 mg given as needed over 12 wk significantly prolonged the stopwatch-assessed intravaginal ejaculatory latency time (IELT) from 0.91 min at baseline to 3.32 min (p < 0.0001), increased control over ejaculation, and increased sexual satisfaction for men and their partners compared with placebo (both p < 0.0001). These results suggest that dapoxetine may meet the medical need for on-demand therapy for PE.     

Pharmacotherapy of premature ejaculation: a systematic review and network meta-analysis

Purpose

The purpose of the study was to conduct a systematic evaluation of the different general prescribed drugs for premature ejaculation (PE).

Methods

A systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for Systematic Reviews was performed on 1 March 2018. Intravaginal ejaculation latency time (IELT) was the main outcome. Analysis was performed under multivariate random-effects network model and efficacies of drugs were ranked with surface under the cumulative ranking (SUCRA) probabilities.

Results

A total of 48 studies were reviewed and 40 of them were further enrolled into network meta-analysis. The majority of RCTs were of unclear methodological quality. Pooled evidence suggested that topical anaesthetic creams (TAs), tramadol, selective serotonin reuptake inhibitors (SSRIs), and phosphodiesterase type 5 inhibitors (PDE5is) are more effective at prolonging IELT comparing with placebo. TAs (90%) on demand (OD) and PDE5is plus SSRI (89.8%) had the highest SUCRA, which meant the most probable to be the most effective intervention.

Conclusions

We recommend the initial use of dapoxetine 30 mg OD for PE because it has been tested in largest and better designed clinical trials rather than it is more effective than the other drugs studied. TAs and tramadol 50 mg OD can be used as a viable alternative to oral treatment with SSRIs. PDE5is combined with SSRIs are more effective than SSRIs monotherapy but are also associated with more side effects. PDE5is OD can be recommended to PE patients with ED.

     

On‐demand d‐modafinil may be an effective treatment option for lifelong premature ejaculation: a case report

Premature ejaculation (PE) is considered to be the most common form of male sexual dysfunction. Given that acute oral administration of d‐isomer of modafinil (d‐modafinil) can extend the latency to ejaculation in rats without suppressing sexual behaviour, the effects of on‐demand d‐modafinil treatment were examined on a 30‐year‐old male patient with lifelong PE. The patient was instructed to take d‐modafinil 100 mg 3 h prior to the sexual relation for four times and was invited for a control visit. The patient was re‐evaluated 2 weeks later. He reported that his IELT increased to 15 min. He reported heartburn and insomnia when he used d‐modafinil for the first time; however, these symptoms were transient and did not recur after the initial dose. Overall, he reported considerable improvement and noted that he feels much better with the treatment. Based on this limited data, on‐demand d‐modafinil seems to be an effective treatment for men with lifelong PE. The side effects were transient and mild in the reported case. Further randomised clinical trials are necessary to elucidate the therapeutic concept of this drug in patients with lifelong PE.     

按需服用达泊西汀对早泄疗效的Meta分析

目的:评价按需服用达泊西汀对早泄的疗效,为临床决策提供依据。方法:检索PubMed、Embase、BIOSIS Previews、Cochrane Library、CNKI数据库、万方资源数据库有关按需服用达泊西汀治疗早泄的研究文献,并进行Meta分析;主要评价阴道内射精潜伏时间(intravaginal ejaculatory latency time,IELT)、患者总体感觉改善情况(patient-reported global impression of change,PGI)、综合临床受益(composite PRO criteria for clinical benefit,CCCB)3项结局指标。结果:检索出相关文献159篇,剔除142篇,共有4篇文献符合纳入标准,累计患者6 081例。Meta分析结果显示:与安慰剂相比,按需服用达泊西汀在IELT[WMD=1.39,95%CI(1.23,1.55),P<0.000 01],PGI[OR=2.59,95%CI(2.21,3.04),P<0.000 01],CCCB[OR=2.59,95%CI(1.98,3.39),P<0.00001]方面差异均有显著性意义;达泊西汀60 mg与30 mg治疗组间比较,60 mg组在IELT[WMD=0.46,95%CI(0.19,0.74),P=0.0010],PGI[OR=1.32,95%CI(1.06,1.64),P=0.01]方面差异有显著性意义,在CCCB[OR=1.39,95%CI(0.90,2.15),P=0.13]方面无显著性差异。结论:本研究表明按需服用达泊西汀60 mg及30 mg均能延长早泄患者IELT,提高其PGI及改善CCCB;其中60 mg较30 mg剂量在延长早泄患者IELT及提高PGI方面效果更佳。     

Relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors treatment on premature ejaculation: decreased nitric oxide is associated with premature ejaculation

The aim of the present study was to determine the relevance of serum nitric oxide levels and the efficacy of selective serotonin reuptake inhibitors (SSRI) treatment on premature ejaculation. Sixty married men (aged 20–50) with lifelong premature ejaculation and forty healthy men (aged 24–48) as control group were included in this study. The patients were evaluated by intravaginal ejaculation latency time (IELT) for premature ejaculation (PE). IELT<1 min is accepted PE. Patients with diabetes mellitus, chronic disorders or erectile dysfunction and heavy smokers were excluded. All patients were evaluated with history, physical examination, International Index of Erectile Dysfunction‐5 (IIEF‐5) score and IELT by stopwatch method. Nitric oxide levels were measured by Griess reaction, and all samples were frozen at ?80 °C. Patients were randomly categorised 4 group to receive fluoxetine 20 mg day^?1 (Group 1), paroxetine 20 mg day^?1 (Group 2), sertraline 50 mg day^?1 (Group 3) and healthy control (Group 4) for 4 weeks. Baseline and post‐treatment findings were compared between the four groups. At the end of 4 weeks, in fluoxetine, paroxetine, sertraline groups mean IELT values showed a statistically significant improvement from the baseline values (P < 0.001, P < 0.001, P = 0.03; respectively). Baseline and 1st month follow‐up mean IIEF scores were 24.5 and 23.05, 24.70 and 23.60 (P < 0.05) in group 1 and group 3 respectively; also 23.09 and 23.32 (P > 0.05) in group 2. Baseline serum NO levels were 31.8, 30.44, 30.8 and 42.84 in fluoxetine, paroxetine, sertraline and healthy control groups respectively. NO levels were statistically lower in patients with PE. After treatment of fluoxetine, paroxetine and sertraline, NO levels were increased baseline (35.8, 36.4, 38.08) (P < 0.05). Our findings indicated that PE is associated with decreased serum NO levels. After the SSRI treatment increased, NO may retard ejaculation presumably by central peripheral mechanism. Further studies are needed to confirm this suggestion and the role of NO in pathophysiology and treatment for premature ejaculation.