Sildenafil citrate (Viagra) for the treatment of erectile dysfunction in Nigerian men

Fifty-eight Nigerian outpatients with documented erectile dysfunction (ED) received open-label sildenafil citrate (Viagra) for 8 weeks. The 50-mg starting dose could be adjusted to 100 or 25 mg based on response and tolerability. The International Index of Erectile Function (IIEF) Questionnaire, a global efficacy question, and intercourse data recorded in a patient event log were used to assess efficacy. Frequency of penetration and maintained erection were both significantly enhanced (P<0.0001); 95% of patients reported improved erections and 81% of all attempts at intercourse were successful. Orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction also improved significantly (P&<0.0001). The most frequent adverse events (all-cause) were headache (17%) and myalgia (3%); only one patient discontinued treatment because of headache, which was considered unrelated to sildenafil. Oral sildenafil significantly improved erectile function and was well tolerated in this trial of Nigerian men suffering from ED. Our results are consistent with reports from other countries.     

Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors

PURPOSE: We determined if pharmacological dosages of phosphodiesterase type 5 inhibitors (PDE5) inhibitors were present within a group of natural products marketed for the treatment of erectile dysfunction. MATERIALS AND METHODS: Seven herbal products marketed for the treatment of erectile dysfunction were purchased via the Internet or at local health food stores. Specimens were batched, relabeled and blindly analyzed for contamination with PDE5 inhibitors. High performance liquid chromatography and mass spectrometry were used to detect evidence of contamination with sildenafil, tadalafil or vardenafil. RESULTS: Of the 7 tested products 2 contained pharmacological dosages of sildenafil and tadalafil. Contamination with vardenafil was not identified. Mean dosages of sildenafil and tadalafil were 30.2 and 19.7 mg, respectively. CONCLUSIONS: A significant proportion of natural products marketed for erectile dysfunction contains PDE5 inhibitors. Although marketed as natural products devoid of adverse effects, these agents are known to have potentially fatal drug interactions with nitrates. Better regulation of the natural health products industry is urged.     

An open-label,multicenter, randomized,crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in Chinese men na?ve to phosphodiesterase 5 inhibitor therapy

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in Chinese men naïve to phosphodiesterase 5 (PDE5) inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire (PITPQ). Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function (IIEF) erectile function (EF) domain, sexual encounter profile (SEP) Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men (91%) completed the randomized treatment phase. Two hundred and forty-two per 350 (69.1%) patients preferred 20-mg tadalafil, and 108/350 (30.9%) preferred 100-mg sildenafil (P < 0.001) as their treatment in the 8 weeks extension. Ninety-two per 242 (38%) patients strongly preferred tadalafil and 37/108 (34.3%) strongly the preferred sildenafil. The SEP2 (penetration), SEP3 (successful intercourse), and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by > 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED naïve to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.     

Molecular pharmacotherapeutic targeting of PDE5 for preservation of penile health

The molecular science of erection physiology has established that phosphodiesterase 5 (PDE5) serves an important biological role in the penis. Current research in the field has revealed this molecular effector to be relevant for penile erection, controlling the erectile response by degrading the second messenger product of the erection mediatory nitric oxide (NO) signaling pathway, 3', 5'-cyclic guanosine monophosphate. Accordingly, PDE5 has been targeted for sexual medicine purposes, and orally administered PDE5 inhibitors such as sildenafil, tadalafil, and vardenafil comprise a foremost intervention for erectile dysfunction (ED). New investigation of PDE5 regulation in the penis has suggested alternative roles for the enzyme and new therapeutic opportunities involving its molecular interactions. In particular, PDE5 function is altered under derangements of androgen deficiency, decreased NO bioactivity, and oxidative stress-associated inflammatory changes, thus contributing to an assortment of erectile disorders including hypogonadism-associated ED, recurrent ischemic priapism, penile vasculopathy, and penile fibrosis. This review provides a critical examination of the multifaceted role of the PDE5 regulatory system in the penis and its relevance for applying existing and emerging therapeutic strategies for erectile disorders.     

Comparative cross-over study of sildenafil and apomorphine for treating erectile dysfunction

OBJECTIVE

To compare the effectiveness, safety and tolerability of sildenafil and apomorphine in Brazilian patients with erectile dysfunction (ED) of various causes.

PATIENTS AND METHODS

In all, 108 patients (mean age 55 years, sd 11) and documented ED for ≥6 months were included in 12 centres in Brazil. The patients were initially followed for 2 weeks and then randomized to initial treatment with apomorphine or sildenafil, taken before sexual intercourse, no more than once a day. The initial dose (2 mg apomorphine and 50 mg sildenafil) could be adjusted (to 3 mg apomorphine, or to 25 or 100 mg for sildenafil) depending on the effectiveness and tolerability during the first 4 weeks of treatment. The patients were re‐evaluated after 8 weeks on treatment and, after a wash‐out period of 2 weeks (no treatment), received the other study drug (other than that received in the first phase), and then had the same procedures as in the first phase.

RESULTS

In all, 97 patients were evaluated for therapeutic effectiveness, the overall effectiveness being assessed using two questions; sildenafil had a significantly higher proportion of affirmative answers for both (P < 0.001). Likewise, the estimates for the mean (sd ) proportion of successful sexual intercourse, of 83.3 (4.7)% vs 40.3 (4.7)% and the total ED Inventory of Treatment Satisfaction score, of 86.7 (2.9) vs 56.9 (2.9) (P < 0.001) were higher for sildenafil. At the end of the study, 93.8% of the patients randomized to initial therapy with apomorphine declared a preference for sildenafil, and 81.3% of those initially treated with sildenafil declared a preference for that drug. The two drugs were well tolerated, and the main adverse events for apomorphine were nausea, vomiting, headache, taste perversion and dizziness; for sildenafil they were headache, flushing or vasodilatation, abdominal pain or dyspepsia and nasal congestion.

CONCLUSIONS

Sildenafil is more effective than apomorphine for treating ED, in the domains of erectile function, satisfaction with sexual intercourse and overall satisfaction, and was the drug preferred by most of the patients.     

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.     

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.

     

Phosphodiesterase type 5 inhibitors for erectile dysfunction

The cyclic nucleotide signalling pathway mediates the smooth-muscle relaxing effects of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is central to the pathophysiology of many forms of erectile dysfunction (ED), which is often associated with other chronic diseases (e.g. hypertension, type 2 diabetes mellitus) and treatments (e.g. certain drugs, radical prostatectomy). Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE-5) promotes erectile responses to sexual stimulation. The successful launch and commercialization of the selective PDE5 inhibitor (PDE5I) sildenafil transformed the treatment of ED, not only by providing an effective, well tolerated oral ED therapy, but also by fostering greater candour about the problem among men. Sildenafil is highly effective in promoting erectile responses across a wide spectrum of severity and causes of ED, including patients with ED that is often refractory to treatment. The recent advent of vardenafil, which has the highest in vitro potency of all available PDE5Is, and tadalafil, which has a prolonged half-life that may enable couples to have sexual activity with less planning, represent further advances. Other PDE5Is offering further potential improvements are under active investigation.     

他达拉非治疗勃起功能障碍:卓越的36小时疗效

磷酸二酯酶5(PDE5)抑制剂是治疗勃起功能障碍(ED)的一线口服药物,与其他两种PDE5抑制剂(西地那非和伐地那非)相比,他达拉非有着起效快、服用方便和疗效显著的特点,但更为突出的是其较长的血浆清除半衰期带来的36h的持续药效,可以使患者和伴侣能更加自由地安排用药时间。患者和伴侣对他达拉非治疗的高满意度可能主要源于对用药时间顾虑的减少和对性生活时程关注度下降等社会心理收益。同时,他达拉非的安全性和耐受性良好,符合安全、有效、方便的用药原则,使其成为大多数ED患者及其伴侣偏爱的首选用药。     

Efficacy and satisfaction rates of oral PDE5is in the treatment of erectile dysfunction secondary to spinal cord injury: a review of literature

Concept

Decreased sexual function is a major concern of men with spinal cord injuries (SCIs). Treatment of erectile dysfunction (ED) through oral pharmacotherapies has been proven to be an effective way to address and treat this concern.

Objective

To find an efficacious and satisfactory treatment ED secondary to SCI through the compilation of studies that utilized the International Index of Erectile Function (IIEF) when testing phosphodiesterase V inhibitors (PDE5i).

Method

Ten articles, which used the IIEF to study satisfaction and/or efficacy of PDE5is sildenafil, tadalafil, and vardenafil in the treatment of ED were reviewed and analyzed. Through the use of a self-made grading scale the value of each article was determined for this research.

Results

Sildenafil, tadalafil, and vardenafil all have been proven to be effective in treating ED in men with SCI. While sildenafil is the most thoroughly studied ED treatment for patients with SCI, tadalafil has a longer time duration effectiveness, which allows for more spontaneity in the sexual experience. Minimal adverse effects have been noted in patients with SCI using these medications; headache, flushing, and mild hypotension are the most common. In articles that study satisfaction, patients show great improvement over baseline with the use of these medications.

Conclusion

Although there is a need for further research on the safety in long-term use of tadalafil and vardenafil, comparative studies done on all three medications show no statistically significant difference in effectiveness or satisfaction. New medications and treatment options, such as avanafil, are being studied in hope of continued improvement of sexual function in men with SCI.     

The effects of phosphodiesterase type 5 inhibitors on penile rigidity variables during a period with no sexual stimulation: a laboratory setting double‐blind study

Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? There is a positive effect of PDE5 inhibitors on several aspects of the men’s sex lives, chiefly erectile function, personal self‐esteem, and satisfaction from their sex lives. To our knowledge, our study is the first study to evaluate the effects of PDE5 inhibitors on erectile variables simultaneously in a laboratory setting. In the present study, significant penile rigidities were obtained with PDE5 inhibitors in a short period, with no sexual stimulation, in laboratory conditions. Our findings might support the use of PDE5 inhibitors in the men who need penile rehabilitation.

OBJECTIVE

To investigate the effects of phosphodiesterase type 5 (PDE5) inhibitors on erectile variables during a period with no sexual stimulation in a laboratory setting double‐blind study.

PATIENTS AND METHODS

In all, 80 men without erectile dysfunction (ED) but with lifelong premature ejaculation (PE) were included in the study. The men were divided equally in to four groups and received either placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double‐blind study design. The men attended the laboratory following 3 days of sexual abstinence and placebo or one of the PDE5 inhibitors was ingested after ≥2 h of fasting and non‐smoking. The men were then immediately placed in a silent room and real‐time penile rigidity and tumescence monitoring with Rigiscan Plus (Rigiscan Plus® System, Osbon Medical Systems, Augusta, GA, USA) began. The men read some magazines or newspapers that contained no sexually stimulating material for 1.5 h. There was no interaction between the men and observer during the test period. Times to first measured and total durations of base and tip rigidities, and also total and per minute rigidity were evaluated.

RESULTS

The recorded base and/or tip rigidity ratios were 40% (eight of 20), 71% (12/17), 47% (nine of 19) and 70% (14/20) in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.126). The ratio of men who could obtain ≥60% base and/or tip rigidities were 10% (two of 20), 41% (seven of 17), 26% (five of 19) and 55% (11/20) in placebo, sildenafil, tadalafil and vardenafil groups, respectively (P < 0.05). The median time to first measured base rigidity was 58.0, 21.5, 54.5 and 57 min with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0032). The median total duration of recorded base rigidity was 4.0, 27.5, 10.0 and 11.5 min in men who took placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.013). The median total base rigidity (area under the curve) was 72.8, 699.0, 360.5 and 553.0 with placebo, sildenafil, tadalafil and vardenafil, respectively (P= 0.016).

CONCLUSIONS

Significant penile rigidities were obtained with PDE5 inhibitors during the short test period, with no sexual stimulation, in laboratory conditions. This finding might support the use of PDE5 inhibitors in men who need penile rehabilitation.     

Efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors in treating erectile dysfunction after bilateral nerve‐sparing radical prostatectomy

We carried out a systematic review and meta‐analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve‐sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double‐blind, placebo‐controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co‐primary efficacy end points: International Index of Erectile Function‐Erectile Function (IIEF‐EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87–5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57–48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3–13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta‐analysis indicates that PDE5 inhibitors to be an effective and well‐tolerated treatment for ED after BNSRP.     

An open-label, randomized, flexible-dose, crossover study to assess the comparative efficacy and safety of sildenafil citrate and apomorphine hydrochloride in men with erectile dysfunction

Two papers in this section deal with well‐known pharmacological agents used to treat male erectile dysfunction. In the first of these, authors from the UK compared the efficacy and safety of sildenafil and apomorphine in such patients. This open‐label crossover trial suggested that sildenafil was better than apomorphine, where the primary endpoint was the erectile function domain of the International Index of Erectile Function. The second paper is an update on the efficacy and safety of tadalafil. It describes the results of its use in a large number of men with erectile dysfunction, compared to placebo. Once again, the erectile function domain was one of the primary endpoints. Tadalafil was an effective and well tolerated treatment for this condition.

OBJECTIVE

To compare the efficacy and safety of sildenafil and apomorphine in the treatment of men with erectile dysfunction (ED).

PATIENTS AND METHODS

In all, 139 men with ED who were naïve to treatment were entered into an open‐label crossover trial with two treatment periods, each of 8 weeks, separated by a 2‐week washout period. Men were randomized to receive either sildenafil then apomorphine or apomorphine then sildenafil, and were allowed to titrate the dose on both drugs. The primary endpoint was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and other endpoints included diary data, the other domains of the IIEF, overall assessment questions and the Erectile Dysfunction Index of Treatment Satisfaction (EDITS) questionnaire.

RESULTS

The EF domain score after treatment was 25.2 for sildenafil and 15.9 for apomorphine. The treatment difference of the adjusted means was 9.3 points (95% confidence interval 7.6–11.1; P < 0.001). After sildenafil the successful intercourse rate was 75%, vs 35% for apomorphine (P < 0.001), and the EDITS scores were 82.5 for sildenafil and 46.8 for apomorphine (P < 0.001). Of the men, 96% expressed a preference for sildenafil as a treatment for their ED. The side‐effect profiles for both drugs were in keeping with published data.

CONCLUSION

By all measurable endpoints sildenafil was superior to apomorphine in this open‐label crossover study of men with ED who were naïve to therapy

     

Oral and injectable medications for the treatment of erectile dysfunction

The treatment of erectile dysfunction has changed dramatically over the past two decades. The introduction of the oral agent sildenafil 2 years ago has revolutionized the treatment of men with compromised erections and has met with expected success and low morbidity. Sildenafil is effective in most men with erectile dysfunction in the general population and in select populations, such as men with spinal cord injury, diabetes mellitus, and patients who have had nerve-sparing radical prostatectomy. It is safe in the general population as well as in many men with cardiac disease. Other newer medications are in trial and may soon be available to supplement treatment with sildenafil. Oral phentolamine, apomorphine, newer phosphodiesterase type-5 inhibitors, and topical agents are currently in phase 3 trials. These agents, in addition to newer intraurethral and indictable agents, may assist men with erectile dysfunction and rescue those in whom sildenafil is ineffective or in whom untoward side effects of sildenafil reduce its effectiveness. The 21st century will witness many additional agents designed for specific patients with specific conditions causing erectile dysfunction. We can expect these oral agents, assisted by topical and injectable agents, to successfully restore erectile function in the majority of men suffering from erectile dysfunction.     

Comparison of the efficacy and safety of sildenafil citrate (Viagra) and oral phentolamine for the treatment of erectile dysfunction

This open-label, multi-center study from Mexico compared the efficacy and safety of oral sildenafil and phentolamine in men with erectile dysfunction. Patients received sildenafil (25-100 mg; n=123) or phentolamine (40 mg; n=119) for 8 weeks, and efficacy was assessed using the International Index of Erectile Function (IIEF) as well as two global efficacy questions. Mean scores for the erectile function domain of the IIEF were significantly higher for sildenafil (27.23 +/- 0.62; P=0.0001) than for phentolamine (19.35 +/- 0.66). Approximately twice as many men receiving sildenafil had successful attempts at sexual intercourse (88% vs 42%), improved erections (95% vs 51.1%), and improved ability to have sexual intercourse (94.4% vs 46.4%) compared with phentolamine. The most common adverse events included rhinitis, headache, tachycardia, and nausea, with a higher frequency reported in patients receiving phentolamine than sildenafil (41% vs 33%), with the exception of headache, which was reported more frequently in sildenafil users. Overall, sildenafil was more effective and appeared to be better tolerated than phentolamine for the treatment of erectile dysfunction.     

按时口服他达拉非治疗按需口服西地那非治疗无效的勃起功能障碍(附15例报告)

目的:总结他达拉非治疗西地那非治疗无效的勃起功能障碍患者的诊疗经验。方法:回顾总结2010年9月至2012年3月15例按需口服西地那非治疗无效的勃起功能障碍患者的病例资料。结果:15例按需口服西地那非治疗无效的勃起功能障碍患者中,11例治疗后勃起功能改善明显,4例改善不明显,有效率73.3%。治疗前后IIEF-5评分比较有显著性差异(P<0.05),疗效满意。4例患者出现不良反应,其中轻微头痛2例,颜面潮红1例,1例出现轻微的腰背痛,均为一过性,继续用药后减轻或消失。结论:按时口服他达拉非是治疗按需口服西地那非治疗无效的勃起功能障碍患者的安全有效方法。     

Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30). RESULTS: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events. CONCLUSIONS: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.     

Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model

Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of erectile dysfunction (ED). In spite of widespread use and generally good efficacy, as a class they remain ineffective in 15-57% of men. Specific cohorts of patients with severe vascular or neurogenic basis to their ED, such as diabetic men or those who have undergone radical pelvic surgery, demonstrate lower response rates with PDE inhibition treatment. We believe that circulating levels of nitric oxide (NO) may be enhanced through delivery of adequate concentrations of free oxygen radical scavenger molecules such as vitamin E. Higher levels of NO, theoretically, should produce increased penile blood flow with the potential for a synergistic effect when combined with a PDE5 inhibitor. With this hypothesis in mind, 20 adult male Sprague-Dawley streptozotocin-induced (60 mg/kg i.p.) diabetic rats were divided into four therapeutic groups (n=5). Group I--control animals received peanut oil, group II--vitamin E 20 IU/day, group III--sildenafil 5 mg/kg/day and group IV--vitamin E 20 IU/day plus sildenafil 5 mg/kg/day, by oral gavage daily for 3 weeks. Erectile function was assessed as a rise in intracavernous pressure following cavernous nerve electrostimulation. Penile tissue was harvested to determine the changes in tissue morphology including neuronal nitric oxide synthase, smooth muscle alpha-actin and endothelial cell integrity. PDE5 protein content and activity were measured. Significant increases in intracavernous pressure were measured in the animals receiving combined vitamin E plus sildenafil treatment. Immunohistochemical staining showed increases of neuronal nitric oxide synthase, endothelial cell and smooth muscle cell staining. Western blot analysis did not show significant differences of PDE5 protein between the groups. However, higher PDE5 activity was measured in the sildenafil group and lower activity of PDE5 was recorded in the cohort receiving vitamin E with sildenafil. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in a meaningful way in this animal model of diabetes. This study indicates a potential means of salvaging erectile function among patients who are refractory to sildenafil.     

Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors

A large body of evidence has accumulated demonstrating that a common pathway in conditions such as hypertension, atherosclerosis, hypercholesterolemia, diabetes mellitus, and erectile dysfunction (ED) is endothelial dysfunction. Although a complete pharmacological cure for ED is currently unavailable, the phosphodiesterase 5 (PDE5) inhibitors sildenafil, vardenafil, and tadalafil are efficacious oral therapy for ED. Results from recent studies suggest that regular treatment with a PDE5 inhibitor may lead to enhanced erectile function (EF) beyond that observed with on-demand usage, possibly through improvement of endothelial function. Such an effect may be viewed as rehabilitation of damaged erectile tissue. The present review focuses on several recent studies which provide evidence for the beneficial effect of regular PDE5 inhibitor administration on the improvement of EF by rehabilitation of vascular endothelium.     

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.