Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study

PURPOSE: Sildenafil is the oral phosphodiesterase-5 inhibitor that revolutionized treatment for erectile dysfunction. We investigated a potential association of the G protein beta 3 subunit (GNB3) C825T polymorphism, a determinant of intracellular signal transduction, with the drug response to sildenafil in patients with erectile dysfunction. MATERIALS AND METHODS: In 113 men with erectile dysfunction and 111 healthy male controls genotype status of the GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction analysis. Patients with erectile dysfunction received sildenafil at a dose of 25 to 100 mg. according to the individual erectile response. Drug response was measured by interviewing the patient according to the erection scale of 0 to 5. RESULTS: The GNB3 genotype distribution of patients with erectile dysfunction exactly matched that of healthy controls. Analysis of the response to sildenafil revealed a significant association of C825T allele status with the erectile response to sildenafil. In the group with TT genotype we observed a 90.9% response but only a 50.9% and 48.9% response in patients with the CC and TC genotype, respectively. The odds ratio for a positive erectile response was 10.0 (95% CI 1.2 to 81.1) for patients with the TT versus the TC/CC genotype (p = 0.01). CONCLUSIONS: The response to sildenafil is significantly associated with GNB3 C825T genotype status in patients with erectile dysfunction.     

Erectile dysfunction and the effects of sildenafil treatment in patients on haemodialysis and continuous ambulatory peritoneal dialysis.

BACKGROUND: Sexual dysfunction, including erectile dysfunction, is common in patients with uraemia. Despite successful treatment of male sexual dysfunction with sildenafil in non-uraemic population, its efficacy in dialysis patients is unknown. PATIENTS AND METHODS: In this study, 35 male HD patients (mean age 48+/-12 years) and 15 male CAPD patients (mean age 44+/-12 years) were included. In the baseline period, haemoglobin, serum urea, and albumin, Kt/V, several hormonal parameters, Beck depression scale, and penile Doppler blood flow, (peak systolic velocity after intracavernous papaverine administration) were measured. The international index of erectile function (IIEF) form was used to evaluate erectile dysfunction. Sildenafil was given to patients with erectile dysfunction at a dose of 50-100 mg/day twice a week. RESULTS: The percentage of erectile dysfunction was similar between patients on HD (71%) and those on CAPD (80%). Patients with erectile dysfunction were significantly older and had lower free-testosterone serum levels and penile blood flow than those without. In linear regression analysis for baseline IIEF score, penile blood flow was the only independent variable associated with erectile dysfunction. IIEF score increased to a similar extent after sildenafil treatment in both HD patients (from 8.10+/-5.54 to 21.70+/-9.61, P<0.001) and CAPD patients (from 9.90+/-3.87 to 21.60+/-10.18, P=0.011). Changes in IIEF scores after sildenafil treatment were associated with baseline penile blood flow as an independent variable by linear regression analysis. Adverse events observed during sildenafil treatment were dyspepsia in two patients and headache in one patient. CONCLUSION: The rate of erectile dysfunction is high in dialysis patients. Penile blood flow is the most important factor for predicting both the development of erectile dysfunction and the response to sildenafil therapy in such patients. Oral sildenafil is an effective, reliable, well-tolerated treatment for uraemic patients with erectile dysfunction.     

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

     

Sildenafil citrate: current clinical experience

There is little question as to the efficacy of sildenafil citrate (Viagra) for the treatment of erectile dysfunction. Two years of post-marketing experience provide data which indicates that the efficacy and safety of sildenafil citrate is consistent with the data obtained in clinical trials. This paper provides an update of the clinical efficacy and safety of sildenafil collected since its market approval in March of 1998. International Journal of Impotence Research (2000) 12, Suppl 4, S62-S66.     

Efficacy, safety and patient acceptance of sildenafil citrate as treatment for erectile dysfunction

PURPOSE: We assessed the efficacy and safety of sildenafil citrate as treatment for erectile dysfunction. MATERIALS AND METHODS: A total of 433 completely evaluated men with chronic erectile dysfunction were treated with sildenafil citrate. Response was assessed prospectively by baseline and followup physician interviews, and by a patient self-administered 15-item questionnaire on the domains of patient treatment response and satisfaction, partner treatment satisfaction, comparative previous treatment satisfaction, adverse effects, and patient and partner quality of life. RESULTS: Of the 304 men (70.2%) who completed the questionnaire 278 received sildenafil, including 186 who previously had undergone treatment for erectile dysfunction, principally involving intracavernous injection therapy. A response was elicited by a median dose of 100 mg. in 188 patients (67.6%) who achieved erection suitable for sexual intercourse. Those with psychogenic erectile dysfunction responded significantly better than those with organic dysfunction (p <0.001). Erection suitable for intercourse was attained by 30.8% of patients with erectile dysfunction after radical prostatectomy and 80% with cavernous veno-occlusive dysfunction. Of previous intracavernous injection responders 29.9% were refractory to sildenafil, while 33. 3% of previous intracavernous injection nonresponders responded to sildenafil. The sildenafil response was considered inferior to the intracavernous injection response by 43.6% of the men who previously responded to intracavernous injection, of whom 51.5% continued to receive intracavernous injection as the only treatment (19.5%) or as an alternative to sildenafil (32%). Adverse effects in 53.6% of cases were assessed as mild in 56.4%, moderate in 38.3% and severe in 5.3%. Multiple adverse effects were reported by 62.4% of patients, while 17 (6.1%) discontinued sildenafil as a direct result of intolerable adverse effects. The most common adverse effects were facial flushing in 33.5% of cases, headaches in 23.4%, nasal congestion in 12.6%, dyspepsia in 10.1% and dizziness in 10.8%. Baseline patient and partner quality of life scores significantly improved after sildenafil treatment (p <0.001), while significantly improved quality of life was noticed by 51.5% and 43.1%, respectively. CONCLUSIONS: Sildenafil citrate is effective oral first line treatment for erectile dysfunction. Although more than 50% of men reported adverse effects, most were considered mild and rarely resulted in treatment cessation. There was a trend in those on intracavernous injection who responded to sildenafil to continue intracavernous injection as the only therapy or as an alternative to sildenafil. Also, we noted that some cases refractory to sildenafil responded to intracavernous injection. These findings imply that intracavernous injection remains an effective erectile dysfunction treatment option.     

Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra)

Objectives. To determine whether the response to the new oral medication, sildenafil citrate (Viagra), was influenced by the presence or absence of the neurovascular bundles, as recent reports on its success did not specify the efficacy of the drug in patients with erectile dysfunction after radical prostatectomy.Methods. Baseline and follow-up data from 28 healthy patients presenting with erectile dysfunction after radical prostatectomy were obtained. Patients receiving any neoadjuvant/adjuvant hormones or adjuvant radiation therapy were excluded. Patients reported what their erectile status was before surgery, before sildenafil therapy, and after using a minimum of four doses of sildenafil. Both the patients and their spouses were interviewed using the Cleveland Clinic post-prostatectomy questionnaire, which includes questions about response to therapy, duration of intercourse, spousal satisfaction, side effects, and related topics. The patients were compared on the basis of the type of surgical procedure they had undergone—nerve sparing or non-nerve sparing. A positive response to sildenafil was defined as erection sufficient for vaginal penetration.Results. Of the 15 patients who had bilateral nerve-sparing procedures, 12 (80%) had a positive response to sildenafil, with a mean duration of 6.92 minutes of vaginal intercourse. These 12 patients also reported a spousal satisfaction rate of 80%. All 12 of the responders had a positive response within the first three doses, and 10 of the 12 responded with the first or second dose. None of the 3 patients who had undergone a unilateral nerve-sparing procedure responded, nor did any of the 10 patients who had undergone a non-nerve-sparing procedure. The two most common side effects of the drug were transient headaches (39%) and abnormal color vision (11%). No patients discontinued the medication because of side effects.Conclusions. Successful treatment of erectile dysfunction in a patient after prostatectomy with sildenafil citrate may depend on the presence of bilateral neurovascular bundles. No patient who had undergone a non-nerve-sparing procedure responded. Whether patients who undergo unilateral nerve-sparing procedures will respond to sildenafil is still unclear because of the small number of patients in our study. These findings should encourage urologists to continue to perform and perfect the nerve-sparing approach. The ability to restore potency with an oral medication after radical prostatectomy will impact our discussion with the patient on the surgical morbidity of radical prostatectomy.     

Is sildenafil citrate associated with an amelioration of the symptomatology of androgen decline in the aging male?

PURPOSE: We examined whether treatment of erectile dysfunction with sildenafil citrate is associated with amelioration of the symptomatology of androgen decline in the aging male, and whether this alters the endocrine pattern. MATERIALS AND METHODS: A double-blind, randomized, placebo controlled, crossover study with sildenafil citrate was conducted in 60 men (age range 47 to 75 years old) who presented with erectile dysfunction and screened positively for androgen decline in the aging male by the questionnaire of the same name. The patients were randomized to receive sildenafil citrate or placebo in a 1:1 ratio and were crossed over after 3 months of treatment for an additional 3 months. The evaluation included International Index Erectile Function and Aging Male Symptoms questionnaires, hormonal profiles, total testosterone, and bioavailable testosterone. RESULTS: A total of 40 patients completed the study. Compared to placebo, sildenafil citrate improved erectile function (52.7 +/- 2 vs 39 +/- 1.9, p <0.001) and Aging Male Symptoms score (33.5 +/- 1.3 vs 28.6 +/- 1.3, p <0.001) in the total group. Breakdown into hypogonadal and normal men showed that the International Index of Erectile Function score improved more in normal (Delta 18.5 +/- 3.6) than in hypogonadal men (Delta 6.7 +/- 2.7). There were no differences in improvement on the Aging Male Symptoms questionnaire between hypogonadal and normal men. No treatment changes were observed in total testosterone and bioavailable testosterone. CONCLUSIONS: In the total group of patients sildenafil citrate was associated with expected improvement in erectile function and in the Aging Male Symptoms questionnaire without any alteration in hormonal pattern. The available questionnaires for androgen decline in the aging male are not specific for the diagnosis of biochemical androgen decline in the aging male, although the suboptimal response to sildenafil citrate suggests the presence of hypogonadism.     

Clinical efficacy of sildenafil in patients on chronic dialysis

PURPOSE: We evaluate the clinical efficacy of sildenafil citrate for patients who are on chronic dialysis and who have concomitant erectile dysfunction. MATERIALS AND METHODS: A total of 35 men (mean age 60.7 years) on dialysis and with erectile dysfunction of various etiologies were administered 25 to 100 mg sildenafil for at least 6 months. The International Index of Erectile Function questionnaire (IIEF), a global assessment question and partner satisfaction question were used to evaluate sildenafil efficacy. Patients also reported any adverse events that occurred during treatment. RESULTS: Treatment was effective for 28 of the 35 (80%) patients according to the results of the IIEF and global assessment questions. Partner satisfaction correlated with the IIEF overall response (0.79) and global assessment question results (0.86). No correlation was found between sildenafil failure and patient age, the etiology of erectile dysfunction, duration of erectile dysfunction, prior treatments, testosterone and prolactin blood levels, and the duration and etiology of renal failure. Of the 35 patients sildenafil was stopped due to intolerable headaches in 3 and because of lack of efficacy in 7. CONCLUSIONS: Sildenafil is an effective and safe treatment for erectile dysfunction in most patients on chronic dialysis.     

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.     

Evaluation of the effectiveness of sildenafil using questionnaire methods versus audio-visual sexual stimulation

AIM: In the present study, an audio-visual sexual stimulation (AVSS) test was used to evaluate the effectiveness of sildenafil, and the AVSS test was coevaluated with the international index of erectile function (IIEF) questionnaire. METHODS: Forty-two patients with erectile dysfunction (ED) were examined (age range, 28-73 years; mean, 51.9 +/- 11.4 years). Each patient answered the IIEF questionnaire and underwent laboratory tests and the AVSS test before administration of sildenafil. The IIEF questionnaire and AVSS test (1 h after administration of 25 mg or 50 mg sildenafil) were re-evaluated in the outpatient clinic 4 weeks later. Questions 3 and 4 of the IIEF test were used to evaluate the effectiveness of sildenafil. Sildenafil was determined to be effective if each score totalled four or five after administration. RESULTS: The rate of effectiveness of sildenafil was 52.4%, and the mean score of the IIEF 5 improved from 7.2 to 15.4 following treatment with sildenafil. The maximum and mean rigidity of the penile tip improved after the sildenafil treatment (36.1%vs 57.7% and 14.2%vs 35.8%, respectively). The maximum and mean rigidity of the penile base rose (42.4%vs 57.7% and 17.9%vs 36.8, respectively). Similarly, following treatment with sildenafil, the penile tumescence increased from 6.6 cm to 7.6 cm at the penile tip and from 7.5 cm to 8.5 cm at the penile base. CONCLUSIONS: In some ED patients the results of the IIEF questionnaire are not always consistent with those of objective evaluation, including AVSS. In these patients, combined assessment using the IIEF and AVSS might be more useful to evaluate the precise effectiveness of sildenafil, rather than relying on the IIEF results alone.     

A dose-escalation study to assess the efficacy and safety of sildenafil citrate in men with erectile dysfunction

OBJECTIVE: To assess the efficacy and safety of sildenafil citrate (Viagra, Pfizer Inc., USA) in a double-blind, placebo-controlled, dose-escalation study over a period of 26 weeks in men with erectile dysfunction of a broad spectrum of aetiology. PATIENTS AND METHODS: In all, 315 patients from five countries were randomized to receive treatment with placebo (156 men) or sildenafil (159 men). Significant concomitant medical conditions were hypertension (20%), a history of pelvic surgery (19%), diabetes mellitus (15%), and ischaemic heart disease (10%). Patients randomized to treatment received a starting dose of 25 mg of sildenafil or matching placebo, which could be increased to 50 mg and then to 100 mg of sildenafil, based on efficacy and tolerability. Assessments of efficacy comprised the 15-item International Index of Erectile Function (IIEF), including question three (ability to achieve an erection) and question four (ability to maintain an erection), a partner questionnaire, an overall efficacy question, and event-log data. RESULTS: After 12 weeks of treatment, 26%, 32% and 42% of patients were taking 25, 50 and 100 mg of sildenafil, respectively. A similar distribution of doses was reported after 26 weeks of treatment. Treatment with sildenafil significantly improved the patients' abilities to achieve and maintain an erection compared with treatment with placebo (P < 0.001). Scores for four of the five sexual function domains of the IIEF (erectile function, orgasmic function, intercourse satisfaction and overall satisfaction) also improved significantly (P < 0.001). There was a significant improvement in the mean score for the erectile function domain, regardless of the aetiology of erectile dysfunction (P < 0.001). After 12 weeks and 26 weeks of treatment, 82% and 79% of patients receiving sildenafil reported improved erections, compared with 24% and 23% of patients receiving placebo, respectively (P < 0.001). Treatment-related adverse events were mild to moderate and occurred in 27% of patients receiving sildenafil, compared with 8% of patients receiving placebo. CONCLUSION: Sildenafil is an effective and well-tolerated treatment for men with erectile dysfunction of a broad spectrum of aetiology.     

Role of sildenafil citrate in treatment of erectile dysfunction after radical retropubic prostatectomy

BACKGROUND: Sildenafil citrate was introduced as a treatment for erectile dysfunction in April 1998 in the United States and has been available since March 1999 in Japan. In this article, we assess the efficacy of sildenafil in the treatment of erectile dysfunction in Japanese men after radical retropubic prostatectomy for localized prostate cancer. METHODS: Of 106 men who underwent radical retropubic prostatectomy between January 1994 and March 2000, 43 were prescribed sildenafil at their request after radical retropubic prostatectomy. Medication was initiated at 25 mg, and if this was ineffective, the dose was increased to 50 mg. Of the patients, 18 underwent bilateral and 21 unilateral nerve sparing (NS) procedures, while in 4 patients, a non-NS procedure was performed. These patients were interviewed using a questionnaire about their response to sildenafil and using the 5-item International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Thirty-three of the 43 patients were eligible for evaluation of the efficacy of sildenafil and 27 completed the IIEF-5 questionnaires. Sildenafil at 50 mg had a better effect on sexual function than 25 mg in most Japanese patients. Of the 16 patients who underwent bilateral NS procedures, 10 (62.5%) had improved ability for intercourse and 3 (18.8%) had improved erections. Of the 13 patients who underwent unilateral NS procedures, 7 (53.8%) had improved ability for intercourse and 4 (30.8%) had improved erections. None of the 4 patients who underwent non-NS procedures had a positive response. Of 24 patients with positive response to sildenafil, 3 (12.5%) did not have to take sildenafil after receiving it because they did not require it for intercourse. Mean IIEF-5 score increased from 4.3 to 11.4 (P < 0.0001). Patient age, time since surgery, PSA and pathological stage did not have statistically significant effects on outcome. The most commonly cited adverse effect was headache (21%). CONCLUSION: Sildenafil is equally effective for erectile dysfunction in Japanese patients who have undergone bilateral and unilateral NS procedures, and aids recovery of natural erectile function after radical retropubic prostatectomy. However, non-NS procedure patients had no response to sildenafil. This study suggested that sildenafil is well tolerated and should be initially used for treatment of Japanese men with erectile dysfunction after radical retropubic prostatectomy.     

全面康复:勃起功能障碍治疗的新目标

5型磷酸二酯酶(PDE5)抑制剂有效改善勃起功能障碍(ED)患者的勃起功能。枸橼酸西地那非的应用范围不断扩展,肺动脉高压已成为新的适应证。临床研究发现,西地那非能改善多种血管性疾病患者的内皮功能。在ED领域的研究进展包括:动物实验发现,西地那非可以改善海绵体内皮功能,增强磷酸化内皮型一氧化氮合酶(eNOS)蛋白表达,逆转缺血或缺氧导致的海绵体内压(ICP)降低。临床研究证实,西地那非可以使50%以上ED患者阴茎勃起恢复到最充分的硬度(4级勃起);使50%以上保留神经的根治性前列腺切除术后患者勃起功能康复,自发产生足以性交的勃起;使ED患者的自尊心、自信心和性关系满意度等社会心理功能恢复正常。从勃起功能到社会心理功能的全面恢复可能成为今后ED治疗的新目标。     

Efficacy, safety and predictive factors of therapeutic success with sildenafil for erectile dysfunction in patients with different spinal cord injuries.

STUDY DESIGN: Multicenter, open, prospective, before-after study. OBJECTIVE: To assess the efficacy and safety of sildenafil therapy for erectile dysfunction in patients with spinal cord injury, and the association between the response to sildenafil and factors such as causes and levels of spinal cord injury, grade of ASIA deficit, time since injury, orgasmic perception, and degree of baseline erection. SETTING: Homes of outpatients of 16 spinal cord injury units in Spain. METHOD: One hundred and seventy patients with erectile dysfunction secondary to spinal cord injury, from whom baseline data were collected on their sexual function, and who started treatment with sildenafil 50 mg. An efficacy assessment was made by the patient and his partner, and the score of the International Index of Erectile Function (IIEF) was recorded. RESULTS: It was reported by 88.2% of the patients and 85.3% of their partners that treatment with sildenafil had improved their erections, regardless of the baseline characteristics of the spinal cord injury and erectile function. In responders, this improvement was confirmed by an increase from 12.5 to 24.8 points (P<0.001) of the Erectile Function Domain of IIEF. A significant improvement was also seen in patients' satisfaction with sexual activity and general satisfaction derived from sexual life. Preservation of orgasmic perception and a baseline degree of erection of 3 or 4 (P=0.006) were predictors of therapeutic success. No serious adverse events occurred. CONCLUSION: Sildenafil is an effective, well-tolerated treatment for erectile dysfunction caused by spinal cord injury, regardless of the cause, neurological level, ASIA grade, and time since injury. SPONSORSHIP: Spanish Society of Paraplegia.     

Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction

OBJECTIVE: To assess the clinical efficacy of sildenafil and the potential predictors of poor response to sildenafil in elderly patients with erectile dysfunction (ED). PATIENTS AND METHODS: The study included 162 patients (aged > or = 60 years) treated with sildenafil for at least 8 weeks; all patients were evaluated with a history, physical examination, measurement of total testosterone and a pharmacological erection test. Sexual function before and 8 weeks after treatment was assessed using the self-administered International Index of Erectile Function (IIEF). Treatment was considered successful when the patient attained a higher grade on the erectile function (EF) domain score, and an affirmative response to the overall assessment question. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. RESULTS: The overall efficacy with sildenafil was 47% (76/162). On univariate analysis, uncontrolled diabetes, current smoking, hypogonadism (<3 microg/L testosterone) and low pretreatment EF domain score (<17) were selected as predictors of a poor response. On multivariate logistic regression, a low pretreatment EF domain score was the strongest independent prognostic factor for a poor response (odds ratio 2.25, 95% confidence interval, 1.45-7.33), and this was followed by hypogonadism (1.89, 1.12-3.16) and current smoking (1.34, 1.04-3.52). CONCLUSION: In a real clinical setting, sildenafil was effective for about half of the elderly men. The baseline EF domain score, hypogonadism and current smoking were significantly associated with failure of sildenafil. These results suggest that modifying reversible risk factors, e.g. stopping smoking and replacing testosterone, would be beneficial in augmenting the efficacy of sildenafil in elderly men.     

A baseline-controlled,open-label,flexible dose-escalation study to assess the safety and efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction

Although sildenafil citrate (Viagra) has demonstrated effectiveness in the treatment of erectile dysfunction (ED), the dosing regimens often used in clinical trials may not always match those employed in clinical practice. This study was undertaken to further assess the efficacy and safety of sildenafil taken as required in male outpatients 18 years of age and older with ED (n=71). It was conducted as a placebo-baseline-controlled, open-label, flexible dose-escalation study, with sildenafil (25,50, or 100 mg) administered for 8 weeks following a 4-week placebo run-in. Efficacy variables included questions 3 and 4 of the International Index of Erectile Function (IIEF), other IIEF domains, patient event logs, and quality-of-life (QOL) assessments. Treatment with sildenafil resulted in improvements from baseline in all IIEF domains analyzed (all P<0.0001), as well as overall QOL and amelioration of specific sexual and social relationships (all P&<0.0001). Sildenafil was well tolerated. One participant discontinued treatment because of adverse events. Results suggest that flexible dosing with oral sildenafil is safe and has beneficial effects on all indices of erectile function and QOL.     

Sildenafil citrate: lessons learned from 3 years of clinical experience

In the 3 y since its initial approval, sildenafil has become the most widely used treatment for erectile dysfunction (ED) and has been prescribed to more than 13 million patients worldwide. Significant improvements in erectile function have been demonstrated in double-blind, placebo-controlled studies in diverse patient populations. A significant treatment effect has been shown with sildenafil in men with ED and a history of diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. In addition, promising results have been shown in patients with treated prostate cancer, end-stage renal disease, Parkinson's disease and spina bifida and in multiple-organ transplant recipients. Postmarketing data of the use of sildenafil in clinical practice confirm the efficacy and safety found in clinical trials and high satisfaction with treatment. Public awareness of the common occurrence of ED and the high likelihood of a potentially favorable response to an oral treatment increased dramatically with the introduction of sildenafil. Physicians, however, are still not comfortable with ED management, which negatively affects pharmacotherapy response rates and patients' compliance to treatment. Continuing medical education seems mandatory to overcome existing problems in ED management.     

Therapeutic effectiveness and patient satisfaction after 6 months of treatment with tadalafil, sildenafil, and vardenafil: results from the erectile dysfunction observational study (EDOS)

OBJECTIVE: This observational study was conducted across Europe to assess health outcomes in men with erectile dysfunction (ED) who took tadalafil, sildenafil citrate (sildenafil), or vardenafil HCl (vardenafil) for 6 mo. METHODS: Therapy effectiveness and patient satisfaction were evaluated using established and new questions on erectile function. Behavioural, psychological, and relationship outcomes were assessed using the short form of the Psychological and Interpersonal Relationship Scales (SF-PAIRS). RESULTS: In nine European countries at 904 sites, 8047 patients were enrolled and 94% (7560) selected either tadalafil (5315), sildenafil (1252), or vardenafil (993) for treatment at baseline. Of the 7560, 3998 (52.9%) took the same drug for 6 mo. Baseline characteristics across the three treatment groups were comparable: mean age approximately 56 yr, moderate or severe ED, and mean International Index of Erectile Function-Erectile Function domain score about 13. Tadalafil, sildenafil, and vardenafil were therapeutically effective and improved patient satisfaction in the 40-58% of men who completed 6 mo of a single therapy. Patients taking tadalafil consistently had numerically higher levels of therapeutic effectiveness and satisfaction compared with patients who took sildenafil or vardenafil. The three cohorts had statistically significant changes from baseline in response to SF-PAIRS and there were significant differences, in favour of tadalafil, among cohorts in the Time Concerns domain. CONCLUSION: In a large observational study that mimics a routine clinical setting, most patients selected an inhibitor of phosphodiesterase 5 to treat ED, which resulted in a high level of therapeutic effectiveness and patient satisfaction.     

SILDENAFIL CITRATE AFTER RADICAL RETROPUBIC PROSTATECTOMY

PURPOSE: Erectile dysfunction continues to be a significant problem for men after radical retropubic prostatectomy despite nerve sparing techniques. Sildenafil citrate (Viagra) has proved effective for erectile dysfunction in many men. We determine the efficacy of sildenafil in men with erectile dysfunction after radical retropubic prostatectomy and examine variables that may impact the response to treatment. MATERIALS AND METHODS: A total of 84 men were prescribed sildenafil after radical retropubic prostatectomy and asked to complete a series of questionnaires, including the International Index of Erectile Function (IIEF), on erectile function before and after sildenafil administration. The importance of factors, such as patient age, time since surgery, degree of cavernous nerve sparing, preoperative prostate specific antigen, Gleason score, clinical and pathological stage, and baseline postoperative erectile function, was examined. RESULTS: Of the 84 patients 45 (53%) had improved erections and 34 (40%) had improved ability for intercourse while taking sildenafil. Mean IIEF score for the erectile function domain increased from 9 to 14 (p <0.001). Orgasmic function (p = 0.004) and intercourse satisfaction (p = 0.009) also significantly improved. The degree of nerve sparing and baseline postoperative erectile dysfunction had a significant impact on the ability of sildenafil to improve erectile function (p = 0.010 and p <0.001, respectively) and total IIEF questionnaire responses (p = 0.031 and p <0.001, respectively). Age and pathological stage also appeared to have a significant effect. CONCLUSIONS: Sildenafil improved erectile function and the ability to have intercourse in more than half of men after radical retropubic prostatectomy. Baseline postoperative erectile function, which is dependent on the degree of nerve sparing technique, significantly impacts the likelihood that patients will respond to sildenafil.     

Sildenafil reduces bother associated with erectile dysfunction: pooled analysis of five randomized, double-blind trials

Improvement in bother associated with erectile dysfunction (ED) is an important aspect of successful treatment of ED. Changes in erectile function and the bother associated with ED were assessed in this analysis of pooled data from five 12-week, multicenter, randomized, double-blind, placebo-controlled, flexible-dose studies of sildenafil. Men who received sildenafil (n=578, vs placebo, n=550) had significantly greater (least squares mean+/-s.e.) improvement in erectile function (EF) domain scores of the international index of erectile function (IIEF) (10.0+/-0.3 vs 1.0+/-0.3, P<0.0001) and in erection distress scale (EDS) total transformed score (18.8+/-0.8 vs 4.8+/-0.9, P<0.0001). Scores on individual questions of the EDS were 24-65% higher after treatment with sildenafil (vs 8-12%, for placebo). The change in EF domain score correlated positively with the change in total transformed EDS score (0.43, P<0.0001). Successful treatment of ED with sildenafil may reduce the bother associated with ED.