Sildenafil: A 4-year update in the treatment of 20 million erectile dysfunction patients

Sildenafil citrate, the first internationally approved and widely used oral agent for the treatment of erectile dysfunction (ED), has revolutionized the treatment of ED throughout the past 5 years. This phosphodiesterase type-5 (PDE-5) inhibitor is selective for corpus cavernosum smooth muscle tissue and produces excellent erectile function. Its efficacy and safety over a wide variety of etiologies of ED and severities of ED demonstrates its usefulness in the clinical treatment of these patients. More than 20 million men have been treated worldwide with sildenafil with excellent results. ED caused by difficult-to-treat etiologies such as radical prostatectomy, severe diabetes, and spinal cord injury have demonstrated efficacy. Although sildenafil citrate, like all PDE-5 inhibitors, is contraindicated in patients taking nitrate medications for cardiac disease, it is effective and safe for those cardiovascular patients who are not taking nitrate medications. The incidence of adverse cardiovascular events in patients taking sildenafil does not differ from those of the general population. Investigations into the pharmacologic effect of sildenafil on coronary myocardial tissue further supports the safety of this medication. Sildenafil has been safe and effective in patients taking various medications including multiple antihypertensive drugs, selective serotonin reuptake inhibitors, cardiac, and diabetic medications.     

Outcome analysis of sildenafil citrate for erectile dysfunction of Japanese patients

The approved maximal dose of sildenafil is only 50 mg in Japan, but the impact of dose regulation on treatment outcomes has not been established. Moreover, the contributors to the efficacy in patients having an intact peripheral nervous system have not been fully elucidated. We assessed in Japanese patients the treatment outcomes of sildenafil for erectile dysfunction (ED) under regulation of the approved dose and identified factors contributing to its efficacy among those with various etiologies other than pelvic surgery. We retrospectively reviewed 196 ED patients treated with sildenafil. The overall efficacy was 70.9% (139/196), and patients with psychological problems and concomitant cardiovascular disease showed high response rates (82.4 and 87.0%, respectively). Of the 139 responders, 89.9% achieved efficacy with a dose of 25 or 50 mg. Logistic regression analysis revealed concomitant cardiovascular disease and a favorable nocturnal penile tumescence result to be independent contributors to the efficacy.     

5型磷酸二酯酶抑制剂治疗勃起功能障碍的疗效和安全性

5型磷酸二酯酶抑制剂使用方便、高效、不良反应小,是治疗勃起功能障碍的一线药物。西地那非自1998年面世以来,是目前研究最透彻的5型磷酸二酯酶抑制剂。临床试验主要针对不同患者群体,包括合并有心血管疾病、糖尿病、抑郁症、前列腺根治术后和透析治疗等特殊人群,进行疗效和安全性研究。不良反应多为轻中度,主要表现为头痛、面部潮红、消化不良和短暂的视觉障碍。本文就5型磷酸二酯酶抑制剂治疗勃起功能障碍的疗效和安全性作一综述。     

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。     

伐地那非治疗难治性勃起功能障碍的最新进展

5型磷酸二酯酶(phosphodiesterase 5,PDE5)在阴茎勃起功能中所起的作用越来越引起人们的关注。环磷酸鸟苷(cGMP)信号通路介导的一氧化氮平滑肌舒张效应是正常勃起功能的必要条件,这个信号通路的下调能引起勃起功能障碍(erectile dysfunction,ED)的许多病理状态,并导致一些慢性疾病的发生。本文回顾了伐地那非治疗ED患者的有效性和安全性。结果表明,伐地那非对于合并异常脂蛋白血症和高血压、糖尿病、抑郁症、前列腺切除术后、外伤性脊髓损伤、西地那非治疗无效、肾移植术后、慢性前列腺炎和早泄的ED患者安全有效,为这些难治性ED患者提供了一种合理的治疗选择。另外,伐地那非还能延长ED患者的勃起时间。     

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.     

The Role of Apomorphine SL in the Treatment of Erectile Dysfunction

Epidemiological data indicate that erectile dysfunction (ED) affects over 140 million men worldwide, with the highest prevalence in men over 60 years. While the condition is often associated with coronary artery disease, hyperlipidemia, hypertension and diabetes, and may be a marker for these conditions, most men who present with ED for treatment have mild to moderate dysfunction. Treatment guidelines developed by an international, multidisciplinary panel of experts as a “process of care model for erectile dysfunction” recommend the implementation of oral agents as first-line therapy. Sublingual apomorphine SL is the first medication for the treatment of erectile dysfunction with a central mechanism of action. In clinical studies, apomorphine SL provides clinical erectogenic benefits at 2 and 3 mg doses particularly in those patients with mild to moderate ED. Apomorphine SL has the added advantages of a rapid onset of action, resulting in erection in less than half the time required by sildenafil, and a highly favorable tolerability and safety profile, especially in patients with coronary artery disease receiving nitrates. Apomorphine SL is an important addition to the armamentarium of primary care clinicians and urologists treating male erectile dysfunction, due to enhanced erectile function, speed of onset, convenience of dosing, and favorable side effect profile. Apomorphine SL 2 and 3 mg is an effective first-line treatment option for men presenting with mild to moderate ED, who have a degree of residual erectile function that is inadequate for satisfactory sexual performance.     

Sildenafil citrate (Viagra) treatment for erectile dysfunction: An updated profile of response and effectiveness

In the 7 years since sildenafil citrate (VIAGRA) was introduced as the first oral phosphodiesterase type 5 inhibitor therapy for erectile dysfunction, it has been used to treat nearly 27 million men with erectile dysfunction worldwide. Patient populations with erectile dysfunction of varying etiologies and with diverse comorbidities have benefited from sildenafil treatment. This update focuses on relatively recent research that further defines the response and effectiveness profiles of sildenafil and provides additional insight into optimizing treatment. In addition to providing recent data on sildenafil efficacy and safety/tolerability, the update provides data on assessments of erection hardness, measures of psychosocial outcomes (e.g., emotional well-being and treatment satisfaction), and treatment approaches to maximize response and effectiveness (e.g., by titrating to the maximum tolerated dose). Increased understanding of the sildenafil response and effectiveness profiles and optimal sildenafil treatment are central to the appropriate management of erectile dysfunction using sildenafil.     

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.     

他达拉非治疗ED的进展

他达拉非是治疗ED的有效药物,大量的研究已经证实了其在ED患者中的临床疗效。相对于西地那非和伐地那非,他达拉非最为显著的特点是它的长效性,接受治疗的ED患者可以在长达36 h的时间窗内自然地达到有效的勃起。他达拉非对患有内科合并症的ED患者具有良好的疗效,它还能有效地改善患者的心理以及晨勃现象,使患者恢复生活的自信。他达拉非的长效性使患者性生活符合“自然、愉快、正常的性生活”这一治疗要求,从而成为越来越多患者的首选药物。     

Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis

OBJECTIVES: Sildenafil is a widely-prescribed effective on-demand treatment of erectile dysfunction (ED). Chronic treatment with sildenafil could help patients with ED. METHODS: The effects of an 8-week long treatment with sildenafil (60 mg/kg/d sc) in male Sprague Dawley rats were evaluated on electrically-elicited erectile responses in vivo before and after an acute injection of sildenafil (0.3mg/kg iv). In addition, endothelium-dependent and -independent relaxations of strips of corpus cavernosum in vitro were examined. All experiments were performed 36 hours after the last injection of sildenafil. RESULTS: Endothelium-dependent relaxations of cavernosal strips to acetylcholine were enhanced after chronic treatment with sildenafil while relaxations to A23187 or sodium nitroprusside were unchanged. Frequency-dependent erectile responses elicited by cavernous nerve stimulation were significantly improved. Moreover, the erectile responses to acute sildenafil were greater in chronically-treated rats with sildenafil. CONCLUSIONS: This is the first report providing experimental support for chronic dosing with sildenafil which could be of use for patients that are poor responders to on-demand treatment. Chronic sildenafil may regulate the transduction pathway leading to the activation of eNOS but has no effect on NO bioavailability or on the cGMP pathway, thereby eliminating a possible concern for tachyphylaxis.     

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.     

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.     

Is sildenafil failure in men after radical retropubic prostatectomy (RRP) due to arterial disease? Penile duplex Doppler findings in 174 men after RRP

Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) erectile dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of erectile dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whether sildenafil failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting with sildenafil refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease. Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency.     

磷酸二酯酶5抑制剂治疗勃起功能障碍的疗效和安全性比较

磷酸二酯酶 5 (PDE 5 )抑制剂西地那非的问世使男性勃起功能障碍 (ED)的治疗手段发生了根本性的改变。1998年以来有 10 0多个国家的 2 0 0 0多万患者使用了西地那非 ,患者的死亡率与总体人群的死亡率差异无显著性。西地那非治疗ED平均有效率达 80 %以上 ,成为治疗ED的首选手段。随着新的PDE 5抑制剂伐地那非和泰地那非在国外先后进入临床使用 ,药物治疗ED有了更多的选择。本文通过比较 3种PDE 5抑制剂的药效学、药动学及不良反应以评价其疗效和安全性。     

西地那非在中国男科临床应用十年回顾

自从10年前西地那非进入中国男科临床以来,其在治疗ED方面的疗效和安全性已被证明,并为国内医生和患者所接受,对各种病因、不同程度、不同年龄的ED患者均具有良好疗效。近年来,西地那非不仅广泛应用于ED治疗上,国内相关研究还显示西地那非在治疗或联合治疗男性早泄等方面也具有一定的疗效,本文在此做一综述。     

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.     

The International Index of Erectile Function (IIEF): a state-of-the-science review

The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for diagnostic evaluation of ED severity. The IIEF was developed in conjunction with the clinical trial program for sildenafil, and has since been adopted as the 'gold standard' measure for efficacy assessment in clinical trials of ED. It has been linguistically validated in 32 languages and used as a primary endpoint in more than 50 clinical trials. This review summarizes early stages in the psychometric validation of the instrument, its subsequent adoption in randomized clinical trials with sildenafil and other ED therapies, and its use in classifying ED severity and prevalence. The IIEF meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity, and correlates well with other measures of treatment outcome. It has demonstrated consistent and robust treatment responsiveness in studies in USA, Europe and Asia, as well as in a wide range of etiological subgroups. Although only one direct comparator trial has been performed to date, the IIEF is also sensitive to therapeutic effects with treatment agents other than sildenafil. A severity classification for ED has recently been developed, in addition to a brief screening version of the instrument. This review includes the strengths as well as limitations of the IIEF, along with some potential areas for future research.