Safety and efficacy of tamsulosin in the treatment of painful ejaculation: a randomized, double-blind, placebo-controlled study

We evaluate the efficacy and safety of tamsulosin a selective alpha(1A)-receptor antagonist in patients with painful ejaculation (PE) as a sole entity. A total of 118 men with PE were included in the study. Patients were randomly assigned to receive 0.4 mg oral daily tamsulosin (group 1, n=59) or placebo (group 2, n=59), during a 6-week period for each agent. Pretreatment evaluation included history and physical examination, International Index of Erectile Function (IIEF) and a visual analog scale (VAS) for pain. The efficacy of two treatments was assessed every 2 weeks during treatment, and at the end of the study using responses to IIEF, VAS evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. In all, 104 patients (88%) completed the whole treatment schedule. Pain resolved in 16 and 13% of the patients treated with tamsulosin and placebo, respectively (P=0.1). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 12 and 10 at 6-week treatment in groups 1 and 2, respectively (P=0.08). The VAS after tamsulosin and placebo decreased from 5.7 and 5.8 to 5.1 and 5.5, respectively (P=0.1). The mean weekly intercourse episodes increased from pretreatment values of 1.8 and 1.6 to 1.9 and 1.7, for tamsulosin and placebo, respectively (P=0.08). Mean number of adverse events was 11 for tamsulosin and 5 for placebo (P<0.05). Tamsulosin is no better than placebo in improvement of PE as a sole entity.     

Safety and efficacy of citalopram in the treatment of premature ejaculation: a double-blind placebo-controlled, fixed dose, randomized study

We evaluate the efficacy and safety of citalopram, a potent and highly selective serotonin reuptake inhibitor (SSRI) antidepressant, in patients with premature ejaculation (PE). In total, 58 potent men with PE were included in the study. Patients were randomly assigned to receive 20 mg oral daily citalopram (group 1, n = 29) or placebo (group 2, n = 29), during a 12-week period for each agent. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IVELT) evaluation, International Index of Erectile Function (IIEF) and Meares-Stamey test. The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of study and in 3- and 6-month follow-up after cessation of treatment, using responses to IIEF, IVELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. The trial was completed by 51 (88%) men. Analysis revealed a difference in the evolution of IVELT delay over time (P < 0.001). The IVELT after citalopram and placebo gradually increased from 32 and 28 s to approximately 268 and 38 s, respectively. The mean weekly intercourse episodes increased from pretreatment values of 1.3 and 1.2 to 2.4 and 1.4, for citalopram and placebo, respectively (P < 0.05). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 16 and 10 at 12-week treatment in groups 1 and 2, respectively (P < 0.05). Mean IVELT in group 1 was 210 and 198 s at 3- and 6-month follow-up, while in group 2 it was 27 and 25 s (P < 0.001), respectively. At 3- and six-month intercourse satisfaction domain values of IIEF were 15 and 14 in group 1 and 10 and 10 (P < 0.05) in group 2, respectively. Group 1 patients reported a significantly higher number of intercourse episodes per week (P < 0.05). Mean number of adverse events was 12 for citalopram and 4 for placebo (P < 0.05). In conclusion, these results indicate that citalopram has significantly better results in terms of IVELT and intercourse satisfaction versus placebo. Further studies with different dosages and treatment regimens are necessary to draw final conclusions on the efficacy of this drug in PE and to prolong the efficacy.     

Salvage of sildenafil failures with cabergoline: a randomized, double-blind, placebo-controlled study

To evaluate the safety and efficacy of cabergoline in men with erectile dysfunction (ED) who did not respond to sildenafil. Four hundred two sildenafil nonresponders aged from 21 to 59 years were included in the study. Patients were randomly divided into group 1, those who received 0.5-1 mg cabergoline weekly for 6 months and group 2, who received placebo for the same period. They underwent preliminary assessment, including medical and sexual history, self-administered International Index of Erectile Function (IIEF) and intravaginal ejaculatory latency time (IVELT) evaluation. Standard biochemistry and hematological laboratory tests, and measurement of serum testosterone and prolactin levels were also carried out. When indicated, other tests were used to establish the diagnosis of vasculogenic and neurogenic ED, including penile color duplex Doppler ultrasonography, pudendal nerve conduction test and impaired sensory-evoked potentials studies. The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of the study, using responses to IIEF, IVELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. The trial was completed by 370 (92%) men. Positive clinical results were seen in 31.2% of patients in the cabergoline group compared with 7.1% of patients in the placebo group (P=0.04). The mean weekly intercourse episodes increased from pretreatment values of 1.4 and 1.2 to 2.2 and 1.4, for cabergoline and placebo, respectively (P=0.04). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 15 and 10 at 6-month treatment in groups 1 and 2, respectively (P=0.04). The IVELT after cabergoline and placebo gradually increased from 98 and 101 s to approximately 242 and 116 s, respectively (P=0.001). More drug-related adverse effects occurred in cabergoline group and 12 (5.9%) had to discontinue treatment (P=0.001). Cabergoline is moderately effective salvage therapy for sildenafil nonresponse. Further studies with different dosages and treatment regimens are necessary to draw final conclusions on the efficacy of this drug in ED.     

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.     

Perceived control over ejaculation is central to treatment benefit in men with premature ejaculation: results from phase III trials with dapoxetine

OBJECTIVES

To assess the utility of perceived control over ejaculation (‘control’) in the evaluation of treatment benefit in men with premature ejaculation (PE), and to compare effects associated with a two‐category or greater increase in this variable between men receiving dapoxetine and placebo.

PATIENTS AND METHODS

This subanalysis used combined data from all treatment groups in an integrated analysis of two identically designed, 12‐week, double‐blind, randomized, placebo‐controlled trials of dapoxetine. Men (2614) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision) criteria for PE, had a stopwatch‐measured intravaginal ejaculatory latency time (IELT) of ≤2 min in ≥75% of events in a 2‐week baseline period, and self‐reported moderate or severe PE. Men received placebo or dapoxetine 30 or 60 mg, 1–3 h before intercourse. The stopwatch‐measured IELT was recorded for each episode; the patient‐reported global impression of change (PGI; 7‐point scale, ‘much worse’ to ‘much better’), control and satisfaction with sexual intercourse (5‐point scales, ‘very poor’ to ‘very good’) were assessed monthly. The utility of a two‐category or greater increase in control was evaluated by examining the relationship of this variable with IELT and satisfaction with sexual intercourse.

RESULTS

Of 2341 men with baseline and endpoint assessments, 96.8% reported ‘very poor’ or ‘poor’ control at baseline, and 748 (32%) reported a two‐category or greater increase in control after treatment. More than 95% of those men rated their PE as ‘slightly better’, ‘better’, or ‘much better’ on the PGI; 67.1% gave ratings of ‘better’ or ‘much better.’ They also had greater improvements in IELT than men with less than a two‐category increase in control, with a mean (sd ) change from baseline of 3.7 (4.3) vs 0.77 (1.8) min, respectively, and a greater percentage reported good or very good satisfaction with sexual intercourse than men with less than a two‐category increase in control (74% vs 19%, respectively). Nausea, headache and upper respiratory tract infection were the most common adverse events reported by men with a two‐category or greater increase in control (15.8%, 7.4% and 6.6%, respectively) and those without (8.5%, 5.5% and 6.5%, respectively). The proportions of men with a two‐category or greater increase in control with dapoxetine 30 and 60 mg were 36.3% and 44.5%, respectively (vs 15% with placebo).

CONCLUSIONS

A two‐category or greater increase in control (5‐point scale) is useful for assessing the treatment benefit in men with PE; it corresponds with improvements in the man’s perception of his condition, substantially greater prolongation of IELT, and higher levels of satisfaction with sexual intercourse.     

PSD502 improves ejaculatory latency,control and sexual satisfaction when applied topically 5 min before intercourse in men with premature ejaculation: results of a phase III,multicentre, double‐blind,placebo‐controlled study

OBJECTIVES

To determine the effect of PSD502 applied topically 5 min before intercourse on the Index of Premature Ejaculation (IPE) and intravaginal ejaculatory latency time (IELT) of men with lifelong premature ejaculation (PE) defined according to the International Society of Sexual Medicine (ISSM) definition; secondary objectives were to evaluate the safety and tolerability of PSD502 in patients with PE, and their sexual partners.

PATIENTS AND METHODS

Men aged >18 years, in stable heterosexual, monogamous relationships, and with lifelong PE diagnosed according to both the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) criteria and the ISSM definition, consented (together with their partners) to enter the baseline period of the study. Patients who documented an IELT of ≤1 min with two or more of the first three sexual encounters during the 4‐week baseline period were randomized, in a 2:1 ratio, to receive double‐blind treatment with PSD502 (three actuations of spray each containing 7.5 mg lidocaine and 2.5 mg prilocaine applied 5 min before intercourse) or placebo for 3 months. Patients completed IPE and Premature Ejaculation Profile (PEP) questionnaires at entry and at monthly clinic visits, and recorded stopwatch‐timed IELT during each sexual encounter. Patients rated the quality of their orgasms on a 5‐point scale at baseline and at the end of the treatment period, and rated the study medication on a 4‐point scale. Safety was assessed by collecting adverse event data.

RESULTS

In all, 300 men with PE were randomized from 31 centres in Europe. The geometric mean (range) IELT over the 3‐month treatment period increased from a baseline of 0.6 min in both groups to 3.8 (0.3–57.8) and 1.1 (0–15.0) min in the PSD502 and placebo groups, respectively. Adjusting for treatment‐group imbalances, this represents a 6.3‐fold and 1.7‐fold increase in adjusted geometric means. There were significantly greater increases in the scores for the IPE domains of ejaculatory control and sexual satisfaction in the PSD502 group than in the placebo group, with a mean (sem ) 7.0 (0.59)‐point difference between treatments in change from baseline in the IPE domain for ejaculatory control and a 5.9 (0.57)‐ point difference in change from baseline in the IPE domain for sexual satisfaction (both P < 0.001). This was supported by improvements in all secondary endpoints. At the end of the treatment period 66% of patients rated PSD502 as ‘good’ or ‘excellent’. PSD502 was well tolerated and no systemic adverse events were reported. Localized treatment‐related adverse events were reported by 2.6% and 3.1% of patients and partners, respectively.

CONCLUSION

PSD502 applied topically 5 min before intercourse improved ejaculatory latency and significantly improved ejaculatory control and sexual satisfaction, factors relevant for acceptance of a PE treatment by both patient/physician and regulatory authorities. PSD502 was well tolerated by both patients and partners, with no systemic side‐effects and a low incidence of localized effects, and was rated favourably by most users. PSD502 therefore appears to offer significant advantages over other therapies in development for the treatment of PE.     

西酞普兰治疗早泄的临床观察

目的:探讨西酞普兰治疗早泄的临床疗效和安全性。方法:将2011年5月至2012年5月男科门诊就诊的80例早泄患者随机分为治疗组和对照组,每组40例。治疗组每天口服西酞普兰20 mg,对照组口服安慰剂,记录治疗前、治疗2周和4周后患者阴道内射精潜伏时间(IELT)和性交满意度分值。结果:治疗组治疗2、4周后IELT分别为(5.64±1.31)min和(7.12±1.56)min,均比治疗前[(0.91±0.18)min]明显延长(P均<0.01),且西酞普兰治疗4周后的IELT明显高于2周后(P<0.01);治疗组治疗2、4周后性交满意度分别为(6.1±1.3)分和(6.3±1.1)分,与治疗前[(2.5±0.8)分]相比有明显提高(P<0.01),而治疗2周和4周后性交满意度无显著性差异(P>0.05)。对照组治疗2、4周后IELT和性交满意度分别为(1.02±0.24)min、1.01±0.21 min和(3.0±1.1)分、(3.1±1.3)分,与治疗前[(0.95±0.17)min和(3.2±1.2)分]比较,均无显著性差异(P均>0.05)。结论:每天口服西酞普兰20 mg,对早泄患者IELT和性交满意度均有明显改善,西酞普兰治疗早泄具有较好的临床疗效和安全性。     

Premature ejaculation: results from a five-country European observational study

OBJECTIVES: To characterize premature ejaculation (PE) in five European countries using intravaginal ejaculatory latency time (IELT) and the Premature Ejaculation Profile (PEP). METHODS: This 8-wk, multicenter, observational study enrolled men >or=18 yr of age and their female partners. Clinicians diagnosed PE using the DSM-IV-TR criteria and at least moderate, subject-reported, ejaculation-related personal distress or interpersonal difficulty. The PEP was administered at baseline and weeks 4 and 8. Partners measured IELT; the average stopwatch-measured IELT for each 4-wk period was calculated and compared with the man's screening-estimated IELT. Relationships between individual PEP measures and IELT were assessed with path analysis. RESULTS: PE was diagnosed in 201 of 1115 men. Findings were similar to those in a similarly conducted US study. Mean IELT was lower in the PE versus the non-PE group (3.3 vs. 10.0min, respectively), but substantial overlap was observed. Men with PE and their partners reported significantly worse control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse, and ejaculation-related interpersonal difficulty than men without PE and their partners. Path analysis showed that perceived control over ejaculation had a significant effect on ejaculation-related personal distress and satisfaction with sexual intercourse; IELT had an effect on control over ejaculation, no direct effect on satisfaction with sexual intercourse, and a small direct effect on ejaculation-related personal distress. CONCLUSIONS: No major cultural differences existed between EU and US men with and without PE and their female partners. These results emphasize the importance of the PEP measures, especially perceived control over ejaculation, in characterizing 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.     

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.     

Relation between blood vitamin B12 levels with premature ejaculation: case–control study

The aim of this study was to investigate whether vitamin B12 levels are associated with premature ejaculation (PE). A total of 109 subjects (56 PE and 53 controls) were included in this study. PE was defined as self‐reported intravaginal ejaculatory latency time (IELT) based on the Diagnostic and Statistical Manual of Mental Disorders IV criteria and those who had had an IELT of <2 min was considered as PE. All participants were evaluated using premature ejaculation diagnostic tool (PEDT), International Index of Erectile Function (IIEF) and Beck Depression Inventory (BDI). The vitamin 12 levels were measured in all subjects. The mean age between the PE and controls was comparable (p = .084). Mean IIEF and BDI scores between the two groups did not statistically differ. The mean IELT values in the PE group were significantly lower than in the control group (p < .0001). PE patients reported significantly lower vitamin B12 levels compared with the controls (213.14 vs. 265.89 ng ml^?1; p < .001). The ROC analysis showed a significant correlation between the diagnosis of PE and lower vitamin B12 levels. This study has demonstrated that lower vitamin B12 levels are associated with the presence of PE. This work also shows a strong correlation between vitamin B12 levels and the PEDT scores as well as the IELT values.     

Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies

OBJECTIVES: To determine the efficacy and safety of fixed-dose oral sildenafil in patients with erectile dysfunction (ED) of various etiologies. METHODS: In a 12-week, double-blind, randomized, placebo-controlled, fixed-dose study, 514 men (mean age 56 years) with ED were randomized to receive 25, 50, or 100 mg of sildenafil or placebo. The primary etiology of ED was determined to be organic in 32% of men, psychogenic in 25%, or mixed in 43%. Sildenafil or placebo was taken in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of the IIEF, a global efficacy question, event log data, and a partner questionnaire. RESULTS: Sildenafil significantly increased patients' ability to achieve and maintain erections (P <0.0001), with efficacy increasing with increasing dose. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction, and overall sexual satisfaction (P <0.0001). The proportion of subjects who felt that treatment with sildenafil improved their erections was significantly greater (67% to 86%) than that with placebo treatment (24%, P <0.0001). The proportion of successful attempts at sexual intercourse also increased significantly with sildenafil treatment (P <0.001). Partner responses corroborated patient reports. Sildenafil was well tolerated at the three doses studied. CONCLUSIONS: Oral sildenafil is an effective, well-tolerated treatment for ED of various etiologies.     

Combination of intralesional verapamil and oral antioxidants for Peyronie's disease: a prospective,randomised controlled study

The aim of this study was to evaluate the efficacy of the association of intralesional verapamil (ILV) injection with oral antioxidants compared with ILV monotherapy in patients with early onset of Peyronie's disease (PD) at 12‐week follow‐up. Group A (n = 52) received ILV 10 mg weekly for 12 weeks, while group B (n = 53) received ILV 10 mg weekly for 12 weeks + antioxidants orally one tablet once a day for 3 months. The main efficacy outcomes were the change in plaque size (PS), penile curvature (PC), visual analogue score (VAS), IIEF‐15 and IIEF‐15 subdomains. Both groups showed significant improvement from baseline to week 12 relative to PS and PC, while group B also in IIEF‐15 score (mean difference: 5.51, P < 0.01) and VAS (mean difference: ?2.71, P < 0.01). No significant differences were observed between both groups in PS and PC. Finally, both groups showed significant increase in orgasmic function (IIEF‐OF) and overall satisfaction (IIEF‐OS), while group B showed significant improvement also in intercourse satisfaction (IIEF‐IS). Significant differences were found relative to IIEF‐OF, IIEF‐IS, IIEF‐OS and VAS scores in the group B compared with group A. Patients affected by PD may benefit from combination treatment with ILV and oral antioxidants thanks to the improvement in IIEF‐OF, IIEF‐IS and IIEF‐OS at 12 weeks.     

Efficacy and safety of flexible-dose oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction in Brazilian and Mexican men

A 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of flexible-dose sildenafil citrate (Viagra) treatment (25, 50 or 100 mg) in Brazilian and Mexican men with erectile dysfunction (ED) of broad-spectrum etiology. Efficacy was assessed on the basis of responses to the 15-item International Index of Erectile Function (IIEF) questionnaire, completed at baseline and after 12 weeks of treatment. At end point, mean scores for all IIEF domains of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) were significantly (P<0.0001) higher in the sildenafil group (n=109) than in the placebo group (n=105). These findings confirm the significant increases in frequency of penetration and frequency of maintained erections reported previously. Sildenafil treatment was well tolerated. The most common adverse events were headache and flushing. In conclusion, sildenafil is a well-tolerated and effective treatment for ED of broad-spectrum etiology in Latin American men.     

Topical eutectic mixture for premature ejaculation (TEMPE): a novel aerosol-delivery form of lidocaine-prilocaine for treating premature ejaculation

OBJECTIVE: To evaluate, in a phase II study, the efficacy and safety of a topical eutectic mixture for premature ejaculation (TEMPE), a metered-dose aerosol spray containing a eutectic mixture of lidocaine and prilocaine, as a treatment for PE. PATIENTS AND METHODS: Men with PE (Diagnostic and Statistical Manual-IV definition) aged 18-75 years were randomized into a double-blind, placebo-controlled study in the UK and the Netherlands. Efficacy variables included the mean change in intravaginal ejaculatory latency time (IELT) from baseline and the proportion of patients who achieved an IELT of > or = 4, > or = 3 or > or = 2 min on two occasions, and the effect of TEMPE on the index of ejaculatory control (IEC) and sexual quality-of-life (SQoL) scores of patients and their partners. Safety and adverse event data were also collected. Fifty-four patients were randomized and received study treatment. RESULTS: The observed mean change in IELT from baseline to the end of the treatment period was 3.8 min in the TEMPE group and 0.7 min in the placebo group, and when adjusted for baseline and centre was 2.4 times higher in the TEMPE than the placebo group (P < 0.01). The efficacy of TEMPE in increasing IELT was further supported by positive trends in the other efficacy endpoints. The proportion of men who had an IELT time > or = 2, > or = 3 or > or = 4 min on two occasions after treatment was 11/20 (55%), 8/20 (40%) and 5/25 (20%) in the TEMPE group, and 8/23 (35%), 3/23 (13%) and 3/23 (13%) in the placebo group, respectively, although these differences were not statistically significant. Improvements in IEC and SQoL (male and female) scores also showed trends towards greater efficacy for TEMPE than placebo. In all, 35 of 42 (83%) patients considered the spray easy to use. Mild to moderate local numbness occurred in three (12%) of the TEMPE-treated patients but did not lead to discontinuation. CONCLUSION: Topical treatment with TEMPE produced a statistically and clinically significant increase in IELT compared with placebo, and resulted in positive trends in ejaculatory control and SQoL. TEMPE was considered easy to use and was well tolerated. The data support the conduct of further large-scale studies to establish the utility of TEMPE as a first-line treatment for PE.     

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.     

Does a constriction ring alter ejaculation latency?

OBJECTIVE: To assess the efficacy of a 'constriction ring' as an option for treating premature ejaculation (PE). PATIENTS AND METHODS: Between September 2003 and October 2006, 42 men with an intravaginal ejaculation latency time (IELT) of <1 min were evaluated. Over a 4-week period, a constriction ring was used during intercourse. RESULTS: The median (range) IELT was 42 (33-54) s before treatment and 46 (31-55) s after 4 weeks of using the ring; there was no statistically significant difference in the IELT before and after treatment (P = 0.1), and no major complications. CONCLUSION: The 'constriction ring' is not an effective treatment for PE.     

Venlafaxine extended release for the treatment of patients with premature ejaculation: a pilot, single-blind, placebo-controlled, fixed-dose crossover study on short-term administration of an antidepressant drug

In this study, we aimed at evaluating the efficacy and safety of venlafaxine extended release 75 mg, a serotonin and noradrenaline reuptake inhibitor, in the treatment of patients with premature ejaculation. Thirty-one patients with intravaginal ejaculation latency of less than 2 min received venlafaxine XR (75 mg/day) or placebo during a 2-week period for each agent with a washout period of 1 week between agents. Efficacy was assessed for each agent with changes in ejaculation latency measured with a stopwatch and sexual satisfaction scores of patients and partners. Side-effects, pre- and post-treatment levels of biochemical and spermiogram parameters, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and total testosterone were recorded for each agent. Statistical analysis was performed on 21 patients. After 2 weeks of treatment with placebo and venlafaxine, ejaculation latency time was significantly increased from 60.1 +/- 39.1 to 126.9 +/- 98.3 sec and to 178.1 +/- 122.8 sec, respectively (p < 0.0001 for each one). However, the difference between the two agents was insignificant (p = 0.144). Venlafaxine and placebo increased sexual satisfaction scores of both patients and partners similarly, no statistically significant difference was found between them in this respect. The incidence of side-effects with venlafaxine was indifferent than that of placebo (p > 0.1) except nausea (p = 0.035). Both agents did not change the blood and spermiogram parameters significantly, except FSH increases. Short-term use of venlafaxine XR 75 mg has only a placebo effect on ejaculation latency and sexual satisfaction scores, therefore, is not appropriate for the patients with premature ejaculation. Further dose-time studies are required to draw final conclusions on the inefficacy of this drug in premature ejaculation.     

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.     

Efficacy and safety of on-demand tadalafil for the treatment of erectile dysfunction in South-East Asian men

AIM: Tadalafil is an inhibitor of phosphodiesterase type 5 used for the treatment of erectile dysfunction (ED). The efficacy and safety of tadalafil have been evaluated extensively in Western populations. Our aim was to assess the efficacy and safety of on-demand tadalafil for the treatment of ED in South-East Asian men. METHODS: This was a randomized, double-blind, placebo-controlled study of men with mild to severe ED of various etiologies randomized to receive placebo (n = 122), tadalafil 10 mg (n = 120), or tadalafil 20 mg (n = 125), taken as needed (maximum once daily) for 12 weeks. Efficacy assessments included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). RESULTS: Men from China, Singapore, and the Philippines participated in this trial (n = 367). Compared with placebo, tadalafil significantly improved erectile dysfunction on all efficacy outcomes (P < 0.001). Patients receiving tadalafil 10 mg and 20 mg experienced a significant mean improvement of 8.1 and 8.7, respectively, in the IIEF Erectile Function (IIEF-EF) domain score from baseline (vs placebo 2.4, P < 0.001). In patients receiving tadalafil 10 mg and 20 mg, the mean per-patient success rate for intercourse attempts (SEP3) was 62% and 70%, respectively, compared with 32% for the placebo group (P < 0.001). Of patients who received tadalafil 10 mg and 20 mg, 81% and 86% reported improved erections at endpoint (GAQ) compared with 44% in the placebo group (P < 0.001). The most common adverse events reported by patients were headache, back pain, dyspepsia, and dizziness. CONCLUSIONS: Tadalafil was an effective and well-tolerated treatment for South-East Asian men with ED.