西地那非治疗勃起功能障碍无效的原因分析及治疗对策

目的 分析按需口服西地那非治疗勃起功能障碍(ED)无效原因并制定治疗策略.方法 2009年1-12月因ED就诊、正确服用西地那非100 mg、至少4次无效的患者126例.采用国际勃起功能指数调查表5个简化问题(IIEF-5)评分、实时勃起功能检测、血清睾酮检测、阴茎多普勒超声检查评估ED治疗无效的原因,患者进行充分的性教育,接受每晚西地那非50 mg治疗.采用IIEF-5评分和性生活日记问题2和3评价再次治疗后的效果.结果 126例ED患者中心理性ED41例,合并睾酮水平低下39例,糖尿病性ED 28例,血管性ED 18例.经过每日小剂量西地那非治疗4周,治疗前后IIEF-5评分分别为(12.3±2.9)分和(18.8±4.4)分,差异有统计学意义(P＜0.05).成功完成性生活者78例,有效率61.9%.结论按需口服西地那非治疗无效的患者经过充分的性教育、长期小剂量治疗后,大部分患者对西地那非治疗仍然有效.

Abstract：

Objective To assess the causes of sildenafil failure and the feasibility of successfully rechallenging non-responding patients. Methods A total of 126 consecutive erectile dysfunction (ED) patients from Jan 2009 to Dec 2009 who claimed poor response to sildenafil (sildenafil 100 mg on demand, at lease 4 epiodes) were enrolled into the study. All patients received sexual reeducation and were treated with sildenafil, taken on a daily dose of 50 mg for 4 weeks. The International Index of Erectile Function-5 (IIEF-5), Rigiscan, serum testosterone or penile Doppler were used to evaluate ED and the cause of on-demand sildenafil failure. End point efficacy of rechallenging was evaluated using the IIEF-5 and the sexual encounter profile (SEP) 'Were you able to insert your penis into your partner's vagina?' and 'Did your erection last long enough to achieve successful intercourse?'. Results The recruited patients comprised of 41 cases with psychological ED, 39 cases with hypogonadism ED, 28 cases with diabetes mellitus ED and 18 cases with vascular ED. Compared with pretreatment and on-demand sildenafil baseline, daily administration of sildenafil significantly enhanced all efficacy outcome variables. The IIEF-5 was significantly improved after daily sildenafil (12.3 ± 2.9 vs18. 8±4.4, P＜0.01), 78 patients responded to daily sildenafil. The overall salvage rate was 61.9%(78/126). Conclusions Sexual reeducation and daily administration of sildenafil may be able to salvage many patients with ED who were sildenafil non-responders.     

Prognostic factors predicting successful response to sildenafil after radical cystoprostatectomy

OBJECTIVES: To assess the efficacy and safety of sildenafil citrate in the management of erectile dysfunction (ED) following radical cystectomy (RC) and to define the different prognostic factors predicting the response to sildenafil in such a challenging group of patients. MATERIAL AND METHODS: One hundred patients with ED following RC participated in an open-label, non-randomized, prospective, dose-escalation study. The median age of the patients was 53 years and the mean period after RC was 80.7 +/- 54.8 months. The study duration was 12 weeks, comprising a 4-week run-in period followed by two active treatment periods of 4 weeks each with 50 and 100 mg of sildenafil. Patients were assessed by means of the International Index of Erectile Function (IIEF) questionnaire at baseline and after each treatment period. At the end of the study, the Global Efficacy Assessment Question was used to evaluate treatment satisfaction. Factors affecting the patient's response to sildenafil were assessed by means of uni- and multivariate analysis. RESULTS: The entire study group was suffering from severe ED at baseline, with a mean erectile function (EF) domain score of 6.5 +/- 0.93. EF scores improved to 12.2 +/- 7.76 and 18 +/- 10.3 with 50 and 100 mg of sildenafil, respectively. Sildenafil therapy significantly improved the ability of many patients to achieve and maintain an erection. The mean scores for question 3 of the IIEF were 1 +/- 0.14, 2.1 +/- 1.4 and 3 +/- 1.8 at baseline and with 50 and 100 mg of sildenafil, respectively, while the corresponding scores for question 4 were 1 +/- 0.10, 1.9 +/- 1.35 and 3 +/- 1.85. The satisfaction rate was 54%. The response was dose-dependent but the incidence of adverse effects increased from 6% with 50 mg of sildenafil to 34% with 100 mg. In univariate analysis, tumor histology and grade and postoperative partial tumescence were found to significantly impact the patient's response to sildenafil. In multivariate analysis, postoperative partial tumescence was the only independent predictive variable. CONCLUSIONS. Sildenafil was found to be a safe and satisfactory treatment for post-RC ED. The effect was dose-related. Patients with postoperative partial tumescence were the best responders.     

High dose sildenafil citrate as a salvage therapy for severe erectile dysfunction

The objectives of this study were to evaluate the efficacy and tolerability of high dose sildenafil as a salvage therapy for patients refractory to the maximum recommended dose of sildenafil. Fifty four fully evaluated patients with chronic erectile failure (ED) who had previously failed to respond to a home trial of sildenafil (100 mg) with erections suitable for sexual intercourse were studied. Each man was treated at home with sildenafil at escalating doses of up to 200 mg until either maximal response or intolerable adverse effects occurred. Erectile function was quantified using the erectile function domain of the International Index of Erectile Function (IIEF) before treatment, with sildenafil 100 mg and with maximal dose of sildenafil and a global efficacy question after 4 weeks of treatment.The mean age of the study group was 59.6+/-11.2 y. 13/54 (24%) had arteriogenic ED, 16/54 (30%) had mixed vasculogenic ED, 9/54 (17%) had cavernosal veno-occlusive dysfunction, 11/54 (20%) had post radical retropubic prostatectomy ED and 5/54 (9%) had psychogenic ED. 13/54 (24.1%) responded to sildenafil at a median maximal dose of 200 mg, 4/13 required 150 mg and 9/13 required 200 mg. 41/54 (76%) failed to respond to sildenafil. Mean IIEF question 3 and 4 scores were 1.5 and 1.4 at baseline, 2.2 and 1.9 with sildenafil 100 mg, 2.8 and 2.5 with sildenafil 150 mg and 3.0 and 2.9 with sildenafil 200 mg, respectively. After 4 weeks, treatment was regarded as having improved their erections by 37%, 46.3% and 68% of patients with sildenafil 100 mg, 150 mg and 200 mg, respectively. 34/54 (63%) reported adverse effects with maximal dose sildenafil comprising headache (19), facial flushing (32), dyspepsia (14), nasal congestion (11), dizziness (5) and visual disturbances (5). 4/13 (31%) responders refused to continue treatment due to adverse effects.In conclusion, sildenafil at doses of up to 200 mg is an effective salvage therapy for 24.1% of previous sildenafil non-responders but is limited by a significantly higher incidence of adverse effects and a 31% treatment discontinuation rate.     

The efficacy of citalopram in the treatment of premature ejaculation: a placebo-controlled study

BACKGROUND: Despite the limited number of available study comparing of their efficacy, selective serotonin re-uptake inhibitors (SSRI) have been thought to have beneficial effects for the patients with premature ejaculation. In the present study, we decided to examine the efficacy of citalopram, an SSRI, in the treatment of premature ejaculation. METHOD: The study was consisted of 26 married patients diagnosed with premature ejaculation according to Diagnostic and Statistical Manual of Mental Disorders Third Revised Version (DSM-III-R). The patients were randomly assigned to two groups, citalopram (group I) and placebo (group II), each consisting of 13 patients. The effects of drug on the ejaculatory function were assessed by the intravaginal ejaculation latency time. Additionally, all patients were screened by using Clinical Global Impression-Improvement Scale (CGI-I) and Yonsei Sexual Function Inventory-II (YSFI-II). RESULTS: The increase in the intravaginal ejaculation latency time in the citalopram group was statistically significant than that of placebo group. In addition, with respect to the subscales of the YSFI-II scale, similar overall significant improvements were seen in the patients given citalopram compared to those given placebo. Of group I patients, five (38.5%) were considered as 'very much improved' and four (30.8%) 'much improved' by CGI-I and only one of group II patients (7.7%) showed 'much improved'. CONCLUSION: The patients treated with citalopram showed significantly greater improvement compared to the patients receiving placebo.     

Rechallenge prior sildenafil nonresponders

To assess inappropriate use as a cause of sildenafil (Viagra ) failure and the feasibility of successfully rechallenging nonresponding patients, a total of 60 consecutive erectile dysfunction (ED) patients who first presented to our hospital and claimed poor response to sildenafil were enrolled into the study. The International Index of Erectile Function-5 (IIEF-5) was used to evaluate their baseline ED status and a self-administered sildenafil-use questionnaire composed of nine questions (SUQ-9) to assess how they had used sildenafil. A total of 44 subjects consent to rechallenge with sildenafil and were given thorough instruction based on individual answers to SUQ-9 and four doses of sildenafil 100 mg. After a 4-week follow-up, end point efficacy of rechallenge was evaluated using the IIEF-5 and the global assessment question (GAQ), 'After the treatment, did you have successful sexual intercourse?' Of the 60 subjects, 44 (77.3%) had one or more areas of major suboptimal use of sildenafil: 18 (30.0%) did not know that sexual stimulation was necessary for sildenafil to work, 36 (60.0%) attempted to use sildenafil less than four times, and 27 (45.0%) took a maximal dose less than 100 mg. Of the 44 patients undergoing sildenafil rechallenge, 34 (77.3%) completed the follow-up, while seven (15.9%) received only GAQ assessment by telephone interview and three (6.8%) were lost to follow-up. The total follow-up rate was 93.2% (41/44). Based on answers to the GAQ, the response rate to rechallenge was 58.5% (24/41). The mean improvement in the IIEF-5 score was 8.4+/-5.5 in responders (P <0.05). With individualized thorough instruction based on answers to SUQ-9 and scheduled follow-up, a high success rate was achieved by rechallenge with sildenafil in prior failures. The efficacy of sildenafil could be improved to a great extent by adequate education of patients and continuing medical education given to primary-care physicians.     

Erectile dysfunction in men with obstructive sleep apnea syndrome: a randomized study of the efficacy of sildenafil and continuous positive airway pressure

The aim of this study was to compare the efficacy of sildenafil and continuous positive airway pressure (CPAP) in men with erectile dysfunction (ED) and obstructive sleep apnea syndrome (OSAS). In all, 30 men were randomly treated for 12 weeks either with sildenafil 100 mg before intercourse (15 men) or CPAP during night time sleep (15 men). Under sildenafil, 97/180 (53.9%) of attempted intercourses were successful compared to 33/138 (23.9%) under CPAP. The mean IIEF (erectile function domain score) was 12.9 and 9.3 after sildenafil and CPAP treatment, respectively (P=0.007), compared to 7.9 and 7 at baseline. In all, 53.3% of patients were satisfied with sildenafil and 20% with CPAP for ED treatment (P=0.058). Although sildenafil was superior to CPAP, comorbidities and OSAS per se possibly resulted in a lower effectiveness of sildenafil compared to that in the general population of ED men. While about half of the patients were not satisfied even with the more effective treatment, we conclude that a combination of the two therapeutic tools or a different therapeutic mode should be studied further.     

Daily use of sildenafil improves endothelial function in men with type 2 diabetes

Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate whether daily use of sildenafil could alter endothelial function and improve penile rigidity in a group of patients with diabetic ED. A double-blind, placebo-controlled, prospective trial was conducted with 24 men with type 2 diabetes who were randomized into 2 groups: one receiving daily sildenafil (50 mg, n = 12) and the other placebo (n = 12) for 10 weeks. Erectile function was captured subjectively using the International Index of Erectile Function (IIEF-5), and endothelial function was objectively monitored via brachial artery flow-mediated dilation. Among the placebo and sildenafil groups, there were no significant differences in average patient age, time from type 2 diabetes diagnosis, duration of ED, or baseline IIEF-5 scores. Past medical histories, including smoking, alcohol consumption, hypertension, and hyperlipidemia, were also similar. At the conclusion of the 10-week trial, patients who received daily sildenafil had significantly improved erectile rigidity as captured by IIEF-5 (P < .001) and increased endothelial function via brachial artery flow-mediated dilation (P < .01). Endothelial function in men with type 2 diabetes was enhanced with daily sildenafil. Improved erectile rigidity and enhanced vascular circulation was noted after 10 weeks of daily sildenafil use.     

Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors.

The objective of this study was to determine the efficacy and safety of sildenafil in patients with erectile dysfunction (ED) and associated organic risk factors in a multispecialty clinic. Patients (n = 521) were diagnosed with ED based on self-assessment. Associated risk factors were managed by medication or life-style modifications, or both, before treatment with sildenafil for ED. Patients received a 50-mg dose of sildenafil that could be adjusted to 100 mg or 25 mg based on tolerability and efficacy. Patients recorded the number of successful intercourse encounters for 6 to 8 weeks, and the number of adverse events. Overall, there was an 82% successful intercourse rate with sildenafil treatment. The predominant associated risk factors for ED were hypertension (39%), hypogonadism (37%), and multiple medications (34%). Common adverse events due to sildenafil treatment were mild to moderate in nature and resulted in <2% patient discontinuation. Clinicians should be particularly careful to evaluate patients presenting with ED because the condition can be accompanied by a wide spectrum of risk factors requiring monitoring and treatment. However, with adequate treatment and control of these risk factors, the use of sildenafil in a representative population of men with ED in a multispecialty clinic can achieve a higher efficacy rate than previous studies have indicated.     

An open-label, multicentre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy

Associate Editor Michael G. Wylie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVES

To compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in men naïve to phosphodiesterase 5 (PDE5) inhibitor therapy.

PATIENTS AND METHODS

This was an open‐label, crossover study of sildenafil and tadalafil (taken as needed). After a 4‐week baseline assessment, 367 men with ED (mean age 54 years) were randomized to receive sildenafil for 12 weeks followed by tadalafil for 12 weeks or vice versa (8‐week dose optimization and 4‐week assessment phases). During dose optimization, patients started taking 25‐ or 50‐mg sildenafil or 10‐mg tadalafil and could titrate to find their optimum dose (25‐, 50‐ or 100‐mg sildenafil; 10‐ or 20‐mg tadalafil). After completing both 12‐week periods, patients chose which treatment to continue during an 8‐week extension. Efficacy was measured with the International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) diary.

RESULTS

Of the 291 men who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose tadalafil (P < 0.001) for the 8‐week extension. The IIEF erectile function domain scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient percentage success scores for SEP2 (penetration) were: baseline (46%), sildenafil (post‐baseline 82%) and tadalafil (post‐baseline 85%; P = 0.06, sildenafil vs tadalafil), and for SEP3 (successful intercourse) were: baseline (19%), sildenafil (post‐baseline 72%), and tadalafil (post‐baseline 77%; P = 0.003, sildenafil vs tadalafil). The only treatment‐emergent adverse events that were reported by >5% of men were headache and flushing.

CONCLUSIONS

In men with ED who were naïve to PDE5 inhibitor therapy, sildenafil and tadalafil were both effective and well tolerated. After treatment with sildenafil and tadalafil, 29% of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8‐week extension.

     

Positive effect of counseling and dose adjustment in patients with erectile dysfunction who failed treatment with sildenafil

OBJECTIVE: Many patients with erectile dysfunction (ED) stop using sildenafil due to subjective failure. This study examined whether counseling and maximal dosing (100 mg) could achieve better treatment compliance and could possibly improve treatment outcome. MATERIAL AND METHODS: Patients were recruited by newspaper advertisements and referred to 5 ED centers throughout the country. Details about their previous experiences with sildenafil were recorded and following an explicit explanation about the nature and action of the drug, were offered to enter the study. Instructions on drug use were provided during each visit in which four 100 mg Sildenafil tablets were provided. Treatment outcomes were assessed by the international index of erectile function (IIEF) questionnaire after taking 4 and 8 tablets. In 2 ED centers a short video with sexual counseling content was added in between visits. RESULTS: The study cohort was comprised of 220 patients aged 27-88 years. The majority reported having received limited or no instructions on drug use when sildenafil was first prescribed. A significant increase in IIEF erectile function domain scores (EFDS) between visits 1, 2 and 3 was observed (10.96+/-0.40, 16.73+/-0.51 and 17.82+/-0.55 mean+/-SE, respectively), with 23.6% of the study patients achieving normal erectile function at the end of the study. The parameters of age and initial severity of ED most influenced treatment success. CONCLUSIONS: Counseling and dose adjustment were directly influential in achieving an excellent response to a second trial of sildenafil in patients with ED who had previously failed treatment with the drug, and obviated their needing to seek more invasive measures.     

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.     

Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction

The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis.     

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.     

Efficacy and safety of oral sildenafil in men with erectile dysfunction and spinal cord injury

OBJECTIVE: To assess the efficacy of sildenafil in men with spinal cord injury (SCI) and erectile dysfunction (ED). METHODS: Seventeen men with SCI were selected from February to September 1998 for sildenafil treatment of ED. The initial dose of 25 mg was increased by 25-mg increments as needed. Patients underwent baseline physical examination and answered questions from the abridged International Index of Erectile Function before and during therapy. RESULTS: Sixteen patients tolerated therapy; 1 developed hypotension and discontinued therapy. There was significant improvement in erectile function (P < .05) after 5.3 +/- 2.2 months when compared with baseline or previous therapies (P < .05). Of the 17 patients, 94% recommended sildenafil to others. Six of these 16 patients were available for long-term follow-up. There was further significant improvement in quality of erection (P < .05), but no change in satisfaction. CONCLUSION: Sildenafil is effective and well tolerated in men with SCI and ED.     

Efficacy of sildenafil in male dialysis patients with erectile dysfunction unresponsive to erythropoietin and/or testosterone treatments

The aim of this study was to evaluate the effects of recombinant human erythropoietin (Epo), testosterone (T) or a combination of them in the treatment of erectile dysfunction (ED) in hemodialysis patients, as well as the efficacy of sildenafil in patients unresponsive to combination treatment. A total of 23 patients with ED were divided into two groups. The international index of erectile function (IIEF) was used to evaluate ED and treatment response. Patients received Epo or T treatments for 12 weeks. Later on both groups received combination treatment for another 12 weeks. Although IIEF scores increased significantly in both groups after the combination treatment, the score changes were similar. After combination treatment, 16 patients still having IIEF score <26 were given sildenafil treatment in combination with Epo while T was discontinued. Although the IIEF scores increased significantly in all patients (17.4%), only eight of them attained an IIEF score of > or =26. The baseline IIEF scores of the patients with satisfactory response to the sildenafil treatment were higher than those with unsatisfactory response. The patients with a score of > or =22 responded better to the treatment. Although Epo and/or T therapies could partially improve ED in male dialysis patients besides correcting renal anemia and hypogonadism, sildenafil treatment could improve ED in unresponsive patients. Especially, those with higher baseline IIEF scores benefited more.     

Combination therapy for erectile dysfunction: a randomized, double blind, unblinded active-controlled, cross-over study of the pharmacodynamics and safety of combined oral formulations of apomorphine hydrochloride, phentolamine mesylate and papaverine hydrochloride in men with moderate to severe erectile dysfunction

Oral therapy has become first line treatment for patients with mild to moderate erectile dysfunction (ED). Studies have shown that sildenafil may not be effective in all patients, and has been associated with a variety of adverse effects and an adverse interaction with nitrates and inhibitors of cytochrome P450 enzymes. The objective was to compare the efficacy and safety of three different oral combinations with the highest dose of sildenafil in men with moderate to severe ED. Randomized, double blind, unblinded active-controlled, Phase II study was carried out at three sites in Mexico. After a 4-week placebo run-in period, patients received all four of the following treatments using a 4-way cross-over design: 40 mg phentolamine (PM) +6 mg apomorphine (Apo); 40 mg PM +150 mg papaverine (Pap); 40 mg PM +6 mg Apo +150 mg Pap (Tricombo); 100 mg sildenafil (SC). With the exception of sildenafil tablets, all study medication was blinded. Moderate to severe ED was defined as a less than 50% vaginal penetration success rate during the placebo run-in period. A total of 44 patients were enrolled, of whom 36 completed all four treatment periods. All treatments produced a significant effect in primary efficacy variable (Sexual Encounter Profile) compared to baseline, however, no statistically significant differences were found between treatments. A significant period effect was observed. Also, the four treatments were found not to differ significantly in five out of six secondary efficacy variables. The lowest incidence of treatment-related adverse events (AE) occurred in the 40 mg PM +6 mg Apo group (9.8%), followed by 100 mg SC (15%), and the other two combinations (16.7 and 17.5%, respectively). Nasocongestion and headache were the most frequently reported AE. An oral combination of vasoactive agents may provide an alternative approach to sildenafil. Based on these results a combination of phentolamine and apomorphine warrants further clinical investigation.     

Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil nonresponders

In a prospective, placebo-controlled, one group crossover design study, we tested whether adding programmed intracavernous PGE1 injections (IC-PGE1) can improve the effectiveness of sildenafil in erectile dysfunction (ED) patients unresponsive to monotherapy with this drug. In all, 40 ED patients who had experienced unsatisfactory erections with both the 50 and 100 mg sildenafil doses were treated with four bi-weekly 20 microg IC-PGE1 injections given in the clinic and provided with either placebo or 50 mg sildenafil capsules for the next 4 weeks. Thereafter, they were crossed over to the other oral treatment for an additional 4-week period. The IIEF-Erectile Function domain score (IIEF-EFS), the main outcome measure, was found considerably higher (P<0.001) with the combined IC-PGE1-50 mg sildenafil treatment than with IC-PGE1-placebo or sildenafil alone (50 or 100 mg) in a subset of 26 subjects (65%). They thus shifted from the 'severe' or 'moderate' to the 'mild' grading of ED classification.     

Efficacy and safety of sildenafil citrate (Viagra) for the treatment of erectile dysfunction in men in Egypt and South Africa

The efficacy of sildenafil citrate (Viagra), an oral agent for the treatment of erectile dysfunction (ED), has been demonstrated in global studies. This 12-week randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study assessed the efficacy and safety of sildenafil to treat ED in men in Egypt and South Africa. Men with ED of varied etiology were randomized to receive sildenafil 50 mg (n=128) or placebo (n=126); doses could be adjusted to 100 or 25 mg. Questions from the International Index of Erectile Function (IIEF) assessing the ability to achieve (Q3) and maintain (Q4) erections demonstrated a significant improvement with sildenafil compared with placebo (P<0.0001). Improved erections were reported by 74% of patients receiving sildenafil and 27% of those receiving placebo (P<0.0001). Headache, dyspepsia, and flushing were the most common adverse events in sildenafil-treated patients. These results are consistent with clinical trials in other countries. We conclude that sildenafil is an efficacious and well-tolerated treatment for men with ED in Egypt and South Africa.     

Factors associated with preference for sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy: post hoc analysis of data from a multicentre, randomized, open-label, crossover study

OBJECTIVES: To determine if baseline characteristics, treatment efficacy, psychosocial outcomes or tolerability were associated with patient preference for sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS: In an open-label, crossover study of sildenafil (25, 50 or 100 mg) and tadalafil (10 or 20 mg), dosed as needed, after a 4-week baseline assessment, 367 men with ED were randomly assigned to sildenafil followed by tadalafil or vice versa (8-week dose optimization and 4-week assessment phase for each treatment period). Patients completing both periods chose which treatment they preferred for an 8-week extension phase. Bivariate logistic regression and stepwise logistic regression were used to determine if any baseline characteristics or post-baseline measurements were associated with the patients' treatment preference. Baseline variables examined were age, race, ED aetiology/duration, body mass index, smoking status, alcohol consumption, vital signs, comorbid medical conditions, and baseline scores for the International Index of Erectile Function (IIEF) domains, Psychological and Interpersonal Relationship Scales (PAIRS) domains, and Sexual Encounter Profile (SEP) diary questions. Post-baseline variables examined were therapy sequence, dosage, and differences in IIEF and PAIRS domains, SEP scores, in number/timing of sexual attempts and in the severity of side-effects (overall patient perception). RESULTS: Of 291 patients completing both treatments and indicating a preference, 85 (29%) preferred sildenafil and 206 (71%) preferred tadalafil. Variables were individually analysed using bivariate analysis; one baseline characteristic (presence/absence of hyperlipidaemia) and 13 post-baseline measurements were significantly associated with the patients' treatment preference. Variables were analysed as a group using stepwise logistic regression; a set of six post-baseline factors was identified as significantly associated with patient preference. Dosage choice, reductions in the PAIRS time concerns domain, IIEF intercourse satisfaction domain improvements, smaller side-effect severity scores, more sexual attempts, and increased SEP4 scores (satisfaction with erection hardness) during the tadalafil or sildenafil treatment periods were all significantly associated with preference for tadalafil or sildenafil. CONCLUSIONS: We identified no baseline characteristics that prospectively distinguish patients who will prefer tadalafil or sildenafil. Patient differences in time concerns, dosage choice, intercourse satisfaction, treatment tolerability, number of sexual attempts and satisfaction with erection hardness were the set of factors most significantly associated with treatment preference, and the preference observed for tadalafil (71%) or sildenafil (29%) might be substantially accounted for by differences in these factors during the tadalafil and sildenafil treatment periods.