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.     

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。     

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.     

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.     

Comparison of the safety and efficacy of the on-demand use of sertraline,dapoxetine, and daily use of sertraline in the treatment of patients with lifelong premature ejaculation: A prospective randomised study

This study compared the safety and efficacy of the on-demand (OD) use of sertraline (50 mg), sertraline (100 mg) and dapoxetine (30 mg), and the daily use of sertraline (50 mg) in the treatment of patients with premature ejaculation (PE). This prospective randomised study involved 120 lifelong PE patients (intravaginal ejaculatory latency time [IELT]: <1 min; Arabic Index of Premature Ejaculation [AIPE] score: < 30) without secondary causes of PE, identified between March 2018 and May 2020. Patients were divided into 4 groups (30 patients per group) and treated for 8 weeks. Assessments were conducted using the AIPE form as a diagnostic tool. Sertraline (50 mg, daily; 196.7 ± 115.5 s) and sertraline (100 mg, OD; 173.3 ± 97.0 s) had similar IELT and AIPE scores. The latter groups had better results in comparison with sertraline (50 mg, OD; 100.5 ± 54.4 s) and dapoxetine (93.7 ± 53.5 s; p < 0.01). Sertraline (100 mg, OD) had a similar efficacy to that of sertraline (50 mg, daily) and was more effective than sertraline (50 mg, OD) and dapoxetine (30 mg, OD). Sertraline (100 mg, OD) can be considered in the treatment of lifelong PE treatment, having tolerable side effects.     

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.     

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.     

Treatment benefit of dapoxetine for premature ejaculation: results from a placebo‐controlled phase III trial

OBJECTIVE

To evaluate the overall treatment benefit of dapoxetine for premature ejaculation (PE), with specific emphasis on improvements in personal distress and interpersonal difficulty related to ejaculation. Although these factors are key elements of numerous sets of diagnostic criteria for PE, they have rarely been evaluated as outcome measures in clinical trials.

PATIENTS AND METHODS

In this randomized, double‐blind, placebo‐controlled, phase III trial we enrolled men aged ≥18 years, from the USA and Canada, who had a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, diagnosis of PE (1238 men). Men were randomized to receive placebo or dapoxetine 60 mg as needed or once daily for 9 weeks. The once‐daily treatment arm was included for analysis of withdrawal symptoms (primary endpoint; presented elsewhere). Patients completed the Premature Ejaculation Profile (PEP) on day 1 (before dosing), and on days 28 and 63 (or study endpoint), which comprised the outcome measures for perceived control over ejaculation, satisfaction with sexual intercourse, and personal distress and interpersonal difficulty related to ejaculation. The patient‐reported global impression of change in PE was reported on day 63 (or study endpoint). Treatment benefit measures included the composite criteria of at least a two‐category increase in perceived control over ejaculation and at least a one‐category decrease in personal distress related to ejaculation from baseline at study endpoint.

RESULTS

At baseline, ≈5% of patients in any treatment group reported ‘not at all’ or ‘a little bit’ of personal distress related to ejaculation, which increased to 54.3% of those receiving dapoxetine (vs 35.3% with placebo; P < 0.001). Similarly, 43.0% and 40.9% of men in the placebo and dapoxetine groups, respectively, reported ‘not at all’ or ‘a little bit’ of interpersonal difficulty related to ejaculation at baseline, which increased to 76.8% and 64.2% of those with dapoxetine and placebo, respectively (P < 0.001). The percentage of men who achieved the composite criteria with dapoxetine ‘as needed’ was 47.6%, vs 21.7% with placebo (difference from placebo, 25.9%; P < 0.001). The distribution of responses for the PEP among men who achieved the composite criteria was similar to that reported for men without PE in a previous observational study in the USA. The most common adverse events were nausea, dizziness, headache, diarrhoea and insomnia, which were more common with dapoxetine than with placebo.

CONCLUSION

Dapoxetine reduced the personal distress and interpersonal difficulty associated with PE, and was associated with patient‐reported improvements in their condition. The percentage of patients who achieved a composite of a two‐category or greater increase in perceived control over ejaculation and a one‐category or greater decrease in personal distress related to ejaculation was substantially greater than with placebo, as were all outcome measures.     

Efficacy and safety of long‐term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction

This study aimed to evaluate the efficacy and safety of long‐term and low‐dose tadalafil combined with sildenafil as needed at the early stage of treatment for erectile dysfunction (ED). We enrolled 180 patients with ED 1 : 1 to tadalafil 5 mg once daily or once‐a‐day tadalafil 5 mg combined with sildenafil 50 mg as needed. The efficacy measures included the 5‐item version of the International Index of Erectile Function (IIEF‐5) and the Sexual Encounter Profile (SEP). The safety was assessed by observing drug tolerability and adverse events. Total IIEF‐5 scores of patients with severe ED in combined medication group were significantly higher than in tadalafil alone group. Question 2 scores of IIEF‐5 of patients with moderate and severe ED in combined medication group were significantly higher than in tadalafil alone group. The significant improvement in question 3 scores of IIEF‐5 existed only in patients with severe ED receiving combined medication. The percentage of ‘yes’ responses to SEP4, SEP5 and partner's SEP3 were improved significantly in combined medication group. There was no difference between two groups in the incidence of adverse events. Our results suggest that combined medication can better improve erectile function, especially for patients with severe ED.     

Can sildenafil treat primary premature ejaculation? A prospective clinical study

BACKGROUND: Recently, sildenafil has been demonstrated to be effective in treating premature ejaculation (PE). However, these studies ignored female factors and could not exclude the probability of drug interaction when combined with paroxetine. Therefore, the aim of this study was to evaluate the efficacy and safety of sildenafil alone in the treatment of primary PE, taking female factors into consideration. METHODS: One hundred and eighty potent men with primary PE were randomly divided into three groups and followed up for 6 months. Group A were treated with 50 mg sildenafil as needed, group B with 20 mg paroxetine daily and group C with squeeze technique daily. Intravaginal ejaculatory latency time (IELT), PE grade, intercourse satisfactory score (ISS), frequency of intercourse, and adverse effects of drugs were recorded before treatment, and 3 and 6 months after treatment. RESULTS: Compared with pretreatment, the three groups had significant differences in all the parameters after 3 or 6 months treatment, except the frequency of intercourse in Group C (all P = 0.00). However, there were no significant differences between 3 and 6 months. Compared with paroxetine and squeeze technique, after 3 or 6 months, sildenafil had significant differences in all the parameters (all P = 0.00). After 6 months, 1.7%, 18.3% and 36.7% patients in groups A, B and C, respectively, withdrew from the study and 86.7%, 60.0% and 45.0% patients, respectively, wanted to be treated further with the original administration, and this was statistically significant (both P = 0.00). CONCLUSION: Sildenafil is very effective and safe to treat PE, and has much higher efficacy than paroxetine and squeeze technique.     

Safety and efficacy of traditional Chinese medicine,Qiaoshao formula,combined with dapoxetine in the treatment of premature ejaculation: An open-label,real-life,retrospective multicentre study in Chinese men

To evaluate the safety and efficacy of Chinese medicine, Qiaoshao formula combined with dapoxetine was used for the treatment of premature ejaculation in a real-life setting. Nine hundred and five males diagnosed with premature ejaculation were reviewed in this retrospective cohort study. We divided the patients into two groups: dapoxetine alone and Qiaoshao formula combined with dapoxetine according to actual interventions provided to patients in clinics. The perceived intravaginal ejaculation latency time and the premature ejaculation profile measures markedly improved in both groups. However, in men with severe premature ejaculation (baseline perceived intravaginal ejaculation latency time <1 min) and those with baseline age ≤30 years, the perceived intravaginal ejaculation latency time was slightly but significantly longer with combined therapy than with dapoxetine alone (p < .05). Therefore, combined therapy involving the Qiaoshao formula and dapoxetine proved to safe as well as effective for treating premature ejaculation while prolonging the perceived intravaginal ejaculation latency time, which significantly improved the overall satisfaction of the patient and likely that of the couple.     

西地那非治疗合并勃起功能障碍的早泄病人的临床观察

目的 :评价枸橼酸西地那非对合并勃起功能障碍 (ED)的早泄病人的临床疗效和安全性。　方法 :45例诊断为合并ED早泄病人 ,以西地那非片可调整用药方案治疗 1～ 3个月。以阴道内射精潜伏期及配偶性交满意度来评价早泄治疗效果 ,并评估ED的总体疗效和治疗满意度 ,比较治疗前后的国际勃起功能指数评分 5 (IIEF 5 )。　结果 :早泄改善者共 2 7例 ,有效率为 6 0 %。勃起功能改善者共 40例 ,改善率为 88.88%。 2 7例早泄有效者均为 5 0mg西地那非改善了勃起功能的病人 ,且满意率为81.48%;18例早泄无效者中ED治疗满意率仅为 5 .5 6 %。在早泄有效者和无效者间比较其治疗前、后IIEF 5评分及增加值 ,差异均有显著性 (P <0 .0 0 1)。不良反应共 9例(2 0 %) ,均为轻度或中度 ,未经特殊处理即自行缓解。　结论 :对合并ED的早泄病人 ,枸橼酸西地那非片能安全有效地改善其勃起功能 ,如获得满意疗效多能使病人早泄得到改善。     

Safety and efficacy of sildenafil citrate in treating erectile dysfunction in patients with combat‐related post‐traumatic stress disorder: a double‐blind,randomized and placebo‐controlled study

OBJECTIVE

To evaluate the safety and efficacy of sildenafil citrate for treating erectile dysfunction (ED) in patients with combat‐related post‐traumatic stress disorder (PTSD).

PATIENTS AND METHODS

In all, 266 combat‐exposed war veterans with ED (aged 37–59 years) were recruited. They met the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria for PTSD according to the Structured Clinical Interview for Patients, Investigator Version. The patients were also evaluated with the Clinician‐Administered PTSD Scale, both to establish the diagnosis of PTSD and to measure symptom severity. Only patients with psychogenic ED were included in the study. Patients with comorbid conditions (diabetes mellitus, hypercholesterolaemia, hypertension, Peyronie’s disease) and smokers of more than five cigarettes daily were excluded. The patients were randomly divided into a group of 133 who received 100 mg of on‐demand sildenafil 0.75–2 h before sexual stimulation, and 133 who received placebo. Patients were asked to use ≥16 doses or attempts at home. The efficacy of the treatments was assessed every four attempts during treatment, and at the end of the study, using responses to the 15‐question International Index of Erectile Function (IIEF), Sexual Encounter Profile diary questions 2 and 3, Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, patients’ event logs of sexual activity, and a Global Assessment Question about erections.

RESULTS

Sildenafil did not produce significantly and substantially greater improvement than placebo in each of the primary and secondary outcome measures (P = 0.08). A normal EF domain score (≥26) at endpoint was reported by 13 (9.8%), and 11 (8.3%) of patients on the sildenafil and placebo regimens, respectively (P = 0.09). Patients treated with sildenafil had no statistically significantly greater improvement in the five sexual function domains of the IIEF questionnaire than those treated with placebo (P = 0.08). The incidences of treatment‐emergent adverse events were significantly greater in the sildenafil arm than in the placebo group (P = 0.01).

CONCLUSIONS

Sildenafil is no better than placebo in treating PTSD‐emergent ED. Further randomized clinical trials are warranted in combat veterans and other populations with PTSD to better elucidate the role of phosphodiesterase type 5 inhibitors in treating PTSD‐emergent ED.     

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.     

Orange peels modulate antioxidant markers and key enzymes relevant to erection in the penile tissue of paroxetine‐treated rats

In comparison to other antidepressant drugs, erectile dysfunction (ED) is more pronounced in paroxetine use. On the other hand, orange (Citrus sinensis) peels commonly consumed in various forms are used in folkloric medicine for ED management. Thus, this study evaluated the effect of orange peels infusion on sexual behaviour, nitric oxide (NO) level and some enzymes (arginase, phosphodiesterase‐5 [PDE‐5], acetylcholinesterase [AChE] and adenosine deaminase [ADA]) in paroxetine‐treated rats. Erectile dysfunction was induced with paroxetine (10 mg/kg body weight). The animals were grouped into five (n = 6): normal rats; paroxetine‐induced rats; paroxetine‐induced rats treated with sildenafil citrate (5 mg/kg); paroxetine‐induced rats treated with orange peels infusion (50 mg/kg); Paroxetine induced rats treated with orange peel infusions (100 mg/kg). The results revealed a significant decrease in sexual behaviour, NO level and the activities of antioxidant enzymes, while there was a significant increase in arginase, PDE‐5, AChE and ADA activities in paroxetine‐induced rats. However, orange peel infusions ameliorated erectile dysfunction in paroxetine‐treated rats. This study showed some possible biochemical basis underlying the use of orange peels infusion in erectile dysfunction management.     

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。     

Efficacy, tolerability and satisfaction with sildenafil citrate 100-mg titration compared with continued 50-mg dose treatment in men with erectile dysfunction

OBJECTIVE

To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED).

PATIENTS AND METHODS

A multicentre, parallel‐group trial was conducted in two 4‐week periods. In period 1, patients received 50‐mg doses of sildenafil single‐blinded for 4 weeks. In period 2, patients were randomized to double‐blind, placebo‐controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged ≥18 years with a documented clinical diagnosis of ED (score of ≤25 on the International Index of Erectile Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria for sildenafil 50 mg and 100 mg.

RESULTS

Of 492 enrolled patients (mean age 53 years, sd 11), 476 (97%) completed period 1 and 473 (96%) completed period 2. Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (sd ) baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) (P < 0.001), and improved scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience Questionnaire (SEX‐Q). The IIEF EF domain scores were similar in the two groups at baseline and randomization. Patients titrated to the 100‐mg dose (237 men) showed a significantly greater improvement than those who continued on the 50‐mg dose (240; P < 0.001). There was a significant increase in QEQ and SEX‐Q scores in patients titrated to sildenafil 100 mg compared with patients continuing at sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes were the most common adverse events. Neither the frequency nor the severity of adverse events increased with titration to sildenafil 100 mg.

CONCLUSIONS

After initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed further increases in efficacy and satisfaction with no increase in the number or severity of adverse events than in those remaining on the starting dose.     

Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors

Potential pharmacokinetic interactions between dapoxetine, a serotonin transporter inhibitor developed for the treatment of premature ejaculation (PE), and the phosphodiesterase-5 inhibitors tadalafil and sildenafil, agents used in the treatment of erectile dysfunction (ED), were investigated in an open-label, randomized, crossover study (n=24 men) comparing dapoxetine 60 mg, dapoxetine 60 mg+tadalafil 20 mg, and dapoxetine 60 mg+sildenafil 100 mg. Plasma concentrations of dapoxetine, tadalafil, and sildenafil were determined by liquid chromatography-tandem mass spectrometry. Tadalafil did not affect the pharmacokinetics of dapoxetine, whereas sildenafil increased the dapoxetine AUCinf by 22%; these effects were deemed not clinically important. Dapoxetine did not appear to affect the pharmacokinetics of tadalafil or sildenafil. Most adverse events were mild in nature. Thus, dapoxetine has no clinically important pharmacokinetic interactions with tadalafil or sildenafil, and the combinations are well tolerated.     

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.     

A comprehensive assessment of genetic variation in serotonin transporter gene (5-HTTLPR+rs25531) and the response to dapoxetine in Chinese patients with premature ejaculation

This study was to explore whether serotonin transporter gene-linked polymorphic region polymorphisms (5-HTTLPR+rs25531) influence the response to dapoxetine treatment in a Chinese population with premature ejaculation (PE). 112 patients with PE re-enrolled from our previous study received dapoxetine monotherapy. At the endpoint, patients with S’S’ had a significant increased risk of nonresponse compared with L’ carriers (p < .001). The improvement in S’S’ genotype was significantly lower in premature ejaculation profile (PEP) items of ‘control over ejaculation’ (p = .035) and ‘distress related to ejaculation’ (p = .017) than that in L’ carriers. As to clinical global impression of change (CGIC), results in S’S’ subjects showed significantly lower scores (p = .008) and a less satisfaction rate reporting at least ‘better’ (p = .020) compared with L’ carriers. Moreover, our findings suggested that patients with S’S’ were more likely to develop adverse effects (AEs) compared with L’ carriers (p = .040). This study suggests that PE patients bearing the S’S’ genotype have an inferior comprehensive efficacy and safety of dapoxetine treatment, which consist of poorer response in IELTs, less improvement in patient-reported outcome (PRO) measures and greater incidence of AEs, than L’ carriers. Variants of triallelic 5-HTTLPR may play a major role as a predictor of treatment response to dapoxetine.