Erectile Dysfunction Of Various Etiologies Research Articles

The Use of Vasoactive Drugs in the Treatment of Male Erectile Dysfunction: Current Concepts.

It is widely accepted that disorders of the male (uro)genital tract, such as erectile dysfunction (ED) and benign diseases of the prostate (lower urinary tract symptomatology or benign prostatic hyperplasia), can be approached therapeutically by influencing the function of both the vascular and non-vascular smooth muscle of the penile erectile tissue or the transition zone/periurethral region of the prostate, respectively. As a result of the discovery of nitric oxide (NO) and cyclic guanosine monophosphate (GMP) as central mediators of penile smooth muscle relaxation, the use of drugs known to increase the local production of NO and/or elevate the intracellular level of the second messenger cyclic GMP have attracted broad attention in the treatment of ED of various etiologies. Specifically, the introduction of vasoactive drugs, including orally active inhibitors of the cyclic GMP-specific phosphodiesterase (PDE) 5, has offered great advantage in the pharmacotherapy of ED and other diseases of the genitourinary tract. These drugs have been proven efficacious with a fast on-set of action and an improved profile of side-effects. This review summarizes current strategies for the treatment of ED utilizing the application of vasoactive drugs via the oral, transurethral, topical, or self-injection route.

Bupropion use in the first trimester of pregnancy

Cavernosal fibrosis is an important pathologic condition leading to erectile dysfunction (ED). The etiologies of cavernosal fibrosis include aging, diabetes mellitus, castration, cavernosal nerve injury during radical prostatectomy, hypertension, and Peyronie disease.To summarize published studies investigating suppression of cavernosal fibrosis in rat models of ED of various etiologies.A literature search was conducted using PubMed. Relevant studies were identified using search terms such as erectile dysfunction, penis, fibrosis, and rat models.We reviewed representative literature studies on the mechanisms and suppression of cavernosal fibrosis in rat models of ED.The underlying mechanisms and potential therapeutic strategies suggested thus far for cavernosal fibrosis in rat models of ED were as follows. For age-related ED involving oxidative stress and tumor growth factor-β1 (TGF-β1)–driven pathways such as RhoA-ROCK1-LIMK2-cofilin or p42-44 and mitogen-activated protein kinase, proposed therapeutic strategies included phosphodiesterase type 5 inhibitors (PDE5Is), kallikrein-kinin system stimulators, and calorie restriction. For diabetes-related ED involving angiotensin-II– and TGF-β1–driven Smad and non-Smad pathways, TGF-β1-Wnt10b, and histone deacetylase (HDAC)-TGF-β1 pathways, positive therapeutic results were obtained with PDE5Is, TGF-β1 antagonists, HDAC inhibitors, antioxidants, sphingosine-1-phosphate receptor modulators (fingolimod), angiotensin-II antagonists, stem cell therapy, and antidiabetic drugs. For cavernosal nerve injury-associated ED involving TGF-β1–driven pathways (Smad or RhoA-ROCK1-LIMK2-cofilin), Sonic hedgehog signaling, angiotensin-II–Smad, and HDAC4–TGF-β1–Smad signaling triggered by cavernosal hypoxia, PDE5Is, angiotensin-II antagonists, stem cell therapy, HDAC inhibitors, Sonic hedgehog administration, ROCK inhibitors, and LIMK2 inhibitors have shown positive results. For testosterone deficiency-associated ED, TGF-β1–driven pathways were found to be responsive to testosterone supplementation. For hypertensive ED, positive therapeutic results were obtained with angiotensin-II antagonists. For Peyronie disease involving TGF-β1 or myostatin signaling, proposed therapeutic strategies included intra-tunical injection of TGF-β receptor inhibitors or adipose tissue-derived stem cells and HDAC2 small hairpin RNA.Several signaling pathways appear to be responsible for the development of cavernosal fibrosis related to ED of various etiologies. Some therapeutic success has been achieved in animal models, but further research focusing on mechanism-specific targeted therapies is needed.Cho MC, Song WH, Paick J-S. Suppression of Cavernosal Fibrosis in a Rat Model. Sex Med Rev 2018;6:572–582.

Suppression of Cavernosal Fibrosis in a Rat Model.

Cavernosal fibrosis is an important pathologic condition leading to erectile dysfunction (ED). The etiologies of cavernosal fibrosis include aging, diabetes mellitus, castration, cavernosal nerve injury during radical prostatectomy, hypertension, and Peyronie disease. To summarize published studies investigating suppression of cavernosal fibrosis in rat models of ED of various etiologies. A literature search was conducted using PubMed. Relevant studies were identified using search terms such as erectile dysfunction, penis, fibrosis, and rat models. We reviewed representative literature studies on the mechanisms and suppression of cavernosal fibrosis in rat models of ED. The underlying mechanisms and potential therapeutic strategies suggested thus far for cavernosal fibrosis in rat models of ED were as follows. For age-related ED involving oxidative stress and tumor growth factor-β1 (TGF-β1)-driven pathways such as RhoA-ROCK1-LIMK2-cofilin or p42-44 and mitogen-activated protein kinase, proposed therapeutic strategies included phosphodiesterase type 5 inhibitors (PDE5Is), kallikrein-kinin system stimulators, and calorie restriction. For diabetes-related ED involving angiotensin-II- and TGF-β1-driven Smad and non-Smad pathways, TGF-β1-Wnt10b, and histone deacetylase (HDAC)-TGF-β1 pathways, positive therapeutic results were obtained with PDE5Is, TGF-β1 antagonists, HDAC inhibitors, antioxidants, sphingosine-1-phosphate receptor modulators (fingolimod), angiotensin-II antagonists, stem cell therapy, and antidiabetic drugs. For cavernosal nerve injury-associated ED involving TGF-β1-driven pathways (Smad or RhoA-ROCK1-LIMK2-cofilin), Sonic hedgehog signaling, angiotensin-II-Smad, and HDAC4-TGF-β1-Smad signaling triggered by cavernosal hypoxia, PDE5Is, angiotensin-II antagonists, stem cell therapy, HDAC inhibitors, Sonic hedgehog administration, ROCK inhibitors, and LIMK2 inhibitors have shown positive results. For testosterone deficiency-associated ED, TGF-β1-driven pathways were found to be responsive to testosterone supplementation. For hypertensive ED, positive therapeutic results were obtained with angiotensin-II antagonists. For Peyronie disease involving TGF-β1 or myostatin signaling, proposed therapeutic strategies included intra-tunical injection of TGF-β receptor inhibitors or adipose tissue-derived stem cells and HDAC2 small hairpin RNA. Several signaling pathways appear to be responsible for the development of cavernosal fibrosisrelated to ED of various etiologies. Some therapeutic success has been achieved in animal models, but further research focusing on mechanism-specific targeted therapies is needed. Cho MC, Song WH, Paick J-S. Suppression of Cavernosal Fibrosis in a Rat Model. Sex Med Rev 2018;6:572-582.

ORIGINAL RESEARCH—ED PHARMACOTHERAPY: Efficacy and Safety of Mirodenafil, A New Oral Phosphodiesterase Type 5 Inhibitor, for Treatment of Erectile Dysfunction

Mirodenafil is a newly developed oral phosphodiesterase type 5 inhibitor, currently under investigation as a treatment for erectile dysfunction (ED). We investigated the efficacy and safety of on demand mirodenafil therapy at fixed doses (50 and 100 mg) in Korean men with a broad range of ED. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted with 223 subjects who were randomized to placebo or mirodenafil at fixed doses of 50 or 100 mg for 12 weeks on an "as needed" basis. Primary efficacy measures were scores on the International Index of Erectile Function (IIEF) Question 3 (Q3) and Question 4 (Q4). Secondary efficacy measures included all domain scores of the IIEF, Sexual Encounter Profile Question 2 (SEP2), Sexual Encounter Profile Question 3 (SEP3), the Global Assessment Question (GAQ), and the Life Satisfaction Checklist (LSC). Safety assessments included laboratory tests, vital signs, physical examination, 12-lead electrocardiogram recordings, and patients' reporting of adverse events. Mirodenafil 50 and 100 mg groups showed a significantly greater increase in IIEF Q3 (P = 0.0001, P < 0.0001, respectively) and Q4 scores (both P < 0.0001) at the end point compared with the placebo group. And mirodenafil in both doses significantly improved the scores of all five domains of the IIEF, SEP2, and SEP3 as well as the percentages of patients responding positively to the GAQ compared with the placebo group. As for LSC scores, the two mirodenafil groups showed significantly greater improvements in items regarding life as a whole, sexual life, and partner relationship than the placebo group. Most treatment-associated adverse events were of mild intensity, resolving spontaneously. Mirodenafil, in doses of 50 or 100 mg, significantly improved erectile function and were well tolerated in a representative population of Korean men with broad-spectrum ED of various etiologies and severities.

Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial

To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED). A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken l h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs. At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P<0.05). Of the 89 patients in the treatment arm, 36 (42.3%) achieved normal erectile function after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients. The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events. The results of our phase II study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.

Prospective, Randomized, Crossover Comparison of Sublingual Apomorphine (3 mg) With Oral Sildenafil (50 mg) for Male Erectile Dysfunction

Purpose We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). Materials and Methods This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. Results Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. Conclusions Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction: a randomized double-blind, parallel, placebo-controlled clinical study

To assess the efficacy and safety of tadalafil in comparison to a placebo, when taken on demand for 12 weeks by East/Southeast Asian men with erectile dysfunction (ED). This multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August 2002 and February 2003. Men more than 18 years of age with mild to severe ED of various etiologies were randomized to receive a placebo or 20 mg of tadalafil taken as needed (maximum once daily). Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile diary and Global Assessment Questions. Tadalafil significantly improved erectile function as compared to the placebo (P < 0.001). At the endpoint, the patients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts (Sexual Encounter Profile question 3: 70.9% compared to 33.5% in the placebo) and a greater proportion of improved erections (Global Assessment Question: 86.2% compared to 30.1%). Most (= or < 3%) treatment emergent adverse events were mild or moderate. The most common treatment emergent adverse events were headache, back pain, dizziness and dyspepsia. Tadalafil was an effective and well-tolerated treatment for ED in East and Southeast Asian men.

Efficacy and safety of on‐demand tadalafil for the treatment of erectile dysfunction in South‐East Asian men

Tadalafil is an inhibitor of phosphodiesterase type 5 used for the treatment of erectile dysfunction (ED). The efficacy and safety of tadalafil have been evaluated extensively in Western populations. Our aim was to assess the efficacy and safety of on-demand tadalafil for the treatment of ED in South-East Asian men. This was a randomized, double-blind, placebo-controlled study of men with mild to severe ED of various etiologies randomized to receive placebo (n = 122), tadalafil 10 mg (n = 120), or tadalafil 20 mg (n = 125), taken as needed (maximum once daily) for 12 weeks. Efficacy assessments included the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). Men from China, Singapore, and the Philippines participated in this trial (n = 367). Compared with placebo, tadalafil significantly improved erectile dysfunction on all efficacy outcomes (P < 0.001). Patients receiving tadalafil 10 mg and 20 mg experienced a significant mean improvement of 8.1 and 8.7, respectively, in the IIEF Erectile Function (IIEF-EF) domain score from baseline (vs placebo 2.4, P < 0.001). In patients receiving tadalafil 10 mg and 20 mg, the mean per-patient success rate for intercourse attempts (SEP3) was 62% and 70%, respectively, compared with 32% for the placebo group (P < 0.001). Of patients who received tadalafil 10 mg and 20 mg, 81% and 86% reported improved erections at endpoint (GAQ) compared with 44% in the placebo group (P < 0.001). The most common adverse events reported by patients were headache, back pain, dyspepsia, and dizziness. Tadalafil was an effective and well-tolerated treatment for South-East Asian men with ED.

Comparison of Efficacy, Safety, and Tolerability of On‐Demand Tadalafil and Daily Dosed Tadalafil for the Treatment of Erectile Dysfunction

To assess and compare the efficacy of on-demand tadalafil and daily tadalafil in the treatment of erectile dysfunction. A total of 145 men with a mean age of 57.3 years (range 19-82 years) and mild to severe erectile dysfunction of various etiologies were randomized to receive on-demand tadalafil (20 mg) or daily tadalafil (10 mg) taken without food or alcohol restrictions in a trial lasting 26 weeks. The three primary outcome measures were changes from baseline in the erectile function domain of the International Index of Erectile Function (IIEF), the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile (SEP). Additional efficacy instruments included a Global Assessment Question administered at completion of the study. Compared with baseline, on-demand and daily tadalafil enhanced all efficacy outcomes. Patients receiving on-demand tadalafil (20 mg) and daily tadalafil (10 mg) experienced a significant mean improvement of 8.3 and 11.9, respectively, in the erectile function domain of the IIEF from baseline (P < 0.001). The mean change from baseline was significantly higher for daily dosed tadalafil than for on-demand tadalafil (P < 0.05). Sexual intercourse was successfully completed (SEP3) in 69% and 84% of patients taking on-demand tadalafil and daily tadalafil, respectively, compared with 30% at baseline (P < 0.001). Successful completion of sexual intercourse was statistically higher for daily tadalafil than for on-demand tadalafil (P < 0.05). Treatment with on-demand tadalafil or daily tadalafil was well tolerated, and headaches, facial flushing, and dyspepsia were the most frequently observed adverse events. Tadalafil was effective and well tolerated in this patient population. Treatment with daily tadalafil was associated with a significantly higher IIEF erectile function domain score and completion of successful intercourse compared with on-demand tadalafil.

PROSPECTIVE, RANDOMIZED, CROSSOVER COMPARISON OF SUBLINGUAL APOMORPHINE (3 mg) WITH ORAL SILDENAFIL (50 mg) FOR MALE ERECTILE DYSFUNCTION

We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Specific aspects of erectile dysfunction in spinal cord injury

According to preliminary studies, the overall incidence of spinal cord injury (SCI; traumatic and medical) in Spain is estimated to be between 12 and 20 per million inhabitants, and almost 80% of these injuries occur in young men. SCI causes organic changes in men leading to erectile dysfunction (ED), impaired ejaculation, and changes in genital orgasmic perception. A vast majority of men with both complete and incomplete SCI will require treatment for ED, and the therapeutic options should include sexual counseling so that the patient can be informed about his disorder and can adjust his sexual behavior accordingly. The first-line treatment of choice is oral drugs, such as phosphodiesterase inhibitors (sildenafil, tadalafil, and vardenafil). Sildenafil has been shown to be highly effective and well tolerated in men with ED of various etiologies, including SCI. Data are also presented on sublingual apomorphine, which has limited indications for the treatment of ED in SCI, and on constrictive rings and vacuum systems. Second-line treatments include intracavernous injections of prostaglandin E(1), papaverine, and phentolamine, alone or in combination, which have been shown to be highly effective in the treatment of ED in men with SCI. Finally, for third-line treatments, the indications for surgical methods are given, including penile prostheses and neuroprosthesis of anterior sacral roots. These devices should be reserved for the cases when the above-mentioned methods have repeatedly failed. Historically, the treatment of ED among patients with SCI has been managed by clinicians in physical medicine and rehabilitation. Thus, the criteria for referral and the competencies of these specialists are established, and they should be included as an integral part of the rehabilitation program.

Efficacy and Safety of On‐Demand Oral Tadalafil in the Treatment of Men with Erectile Dysfunction in Taiwan: A Randomized, Double‐Blind, Parallel, Placebo‐Controlled Clinical Study

Tadalafil is a phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction (ED). Past clinical trials have assessed its efficacy and safety in western populations. Tadalafil has not been investigated in a large clinical trial with a South-east Asian population. To assess the efficacy and safety of on-demand tadalafil for the treatment of ED in a 12-week, double-blind, placebo-controlled study in Taiwan. Men with mild to severe ED of various etiologies were randomized to receive placebo, tadalafil 10 mg, or tadalafil 20 mg, taken as needed (maximum once daily). Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile (SEP) diary, and a Global Assessment Question (GAQ). Tadalafil significantly improved erectile function compared with placebo (P < 0.005, all measures). At endpoint, the patients receiving tadalafil reported a greater mean per-patient percentage of successful intercourse attempts (SEP question 3: 70.0%, 10 mg; 78.0%, 20 mg) than placebo-treated patients (42.8%) and a greater proportion of improved erections (GAQ: 92.3% and 84.6% vs. 54.5%). Most treatment-emergent adverse events were mild or moderate. The most common adverse events were back pain, dyspepsia, and myalgia. Tadalafil was an effective, well-tolerated therapy for men in Taiwan with ED of broad-spectrum severity and etiology.

Is Quality if Life Different for Men with Erectile Dysfunction and Prostate Cancer Compared to Men with Erectile Dysfunction Due to Other Causes? Results from the ExCEED Data Base

To our knowledge the relationship between the underlying etiology of erectile dysfunction and its impact on health related quality of life has not been studied. Such a study is important for men with prostate cancer, as the potential negative quality of life impact of erectile dysfunction may affect clinical decision making in newly diagnosed disease. We compare health related quality of life in impotent men with prostate cancer to that of impotent men without prostate cancer using the Exploratory and Comprehensive Evaluation of Erectile Dysfunction (ExCEED, TAP Pharmaceutical Products, Inc., Lake Forest, Illinois) data base, which is a multicenter, observational disease registry of men with erectile dysfunction. The cohort included 168 men in ExCEED who had baseline health related quality of life measurement. Of these men 47 reported a history of prostate cancer while 121 did not. Appropriate univariate and multivariate analyses were performed comparing health related quality of life outcomes between impotent men with and without prostate cancer. Men with erectile dysfunction and prostate cancer had worse sexual self-efficacy, erectile function, intercourse satisfaction and orgasmic function than those with erectile dysfunction without prostate cancer (all p <0.001). However, men with erectile dysfunction and prostate cancer experienced less psychological impact of erectile dysfunction on sexual experience (p = 0.05) and emotional life (p = 0.03) than those with erectile dysfunction without prostate cancer. The findings regarding the psychological impact of erectile dysfunction persisted in multivariate linear regression models. Men with erectile dysfunction and prostate cancer appear to have better disease specific health related quality of life than those with erectile dysfunction and no history of prostate cancer. This finding has important ramifications for clinicians when counseling patients newly diagnosed with prostate cancer and also when treating patients who present with erectile dysfunction of various etiologies.

Tadalafil Phase 3 Experience

Objectives: To evaluate the efficacy and safety of tadalafil, a potent, oral phosphodiesterase type 5 inhibitor for erectile dysfunction. Methods: Integrated analyses of five 12-week, randomized, double-blind, placebo-controlled phase 3 clinical trials involving 1112 men with mild-to-severe erectile dysfunction of various etiologies taking as-needed tadalafil 2.5, 5, 10 or 20 mg ( n=804) or placebo ( n=308) were conducted. Results: Tadalafil therapy significantly enhanced erectile function (versus placebo), eliciting robust changes that were consistent across a number of efficacy outcome measures. Ratings of erectile function, the likelihood of successfully completing intercourse, and proportions of men reporting enhanced erectile function were significantly higher in tadalafil patients compared with placebo controls. Eighty-one percent of all men who were treated with tadalafil 20 mg reported improved erections at study endpoint compared with 35% of placebo controls. Tadalafil was well tolerated, with headache and dyspepsia being the most frequent treatment-emergent adverse events. These events tended to be mild or moderate and to abate with continued dosing. Conclusions: Tadalafil therapy significantly ameliorated erectile function and was well tolerated by a broad spectrum of men with erectile insufficiency.

Efficacy and Safety of Tadalafil for the Treatment of Erectile Dysfunction: Results of Integrated Analyses

We conducted integrated analyses of the efficacy and safety of tadalafil, a potent, selective phosphodiesterase 5 inhibitor, for the treatment of erectile dysfunction. A total of 1,112 men with a mean age of 59 years (range 22 to 82) and mild to severe erectile dysfunction of various etiologies were randomized to placebo or tadalafil, taken as needed without food or alcohol restrictions, at fixed daily doses of 2.5 mg, 5 mg, 10 mg, or 20 mg up to a maximum of once daily [DOSAGE ERROR CORRECTED] in 5 randomized, double-blind, placebo controlled trials lasting 12 weeks. The 3 co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function and the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile. Additional efficacy instruments included a Global Assessment Question. Compared with placebo, tadalafil significantly enhanced all efficacy outcomes. Patients receiving 20 mg. tadalafil experienced a significant mean improvement of 7.9 in International Index of Erectile Function erectile function domain score from baseline (p <0.001 versus placebo), 75% of intercourse attempts (Sexual Encounter Profile question 3, a secondary efficacy outcome) were successfully completed (p <0.001 versus placebo) and 81% reported improved erections at end point compared with 35% in the control group (p <0.001). Tadalafil was consistently efficacious across disease severities and etiologies, as well as in patients of all ages. Tadalafil was well tolerated, and headache and dyspepsia were the most frequent adverse events. Tadalafil was effective and well tolerated in this patient population.

Erectile dysfunction: oral pharmacotherapy options.

Erectile dysfunction (ED) (impotence) is a widespread, age-related problem, which affects 52% of men between 40 and 70 years of age. It is classified as psychogenic, organic, or mixed psychogenic and organic. ED is not a problem only of men, because the relationship between partners can also be disturbed. Therefore, adequate treatment of ED is needed and the most convenient and simplest way is oral drug therapy. Sildenafil, phosphodiesterase-(PDE)-5-selective inhibitor has been the drug of choice for patients with ED since it has been launched in March 1998. The results of various studies have confirmed the efficacy of the drug in men with ED of various etiologies, as well as the positive effect of sildenafil on the quality of a partnership. The most frequent adverse effects documented with sildenafil usage are headache, flushes, dyspepsia, visual disturbances and nasal congestion/rhinitis. These adverse effects are dose-related, usually transient and mild, with low withdrawal rate. Several studies performed recently have shown that sildenafil is a safe and effective treatment of ED in patients with cardiovascular disease, who do not take nitrates or nitrate donors concomitantly. Other oral medications for ED include apomorphine, phentolamine, yohimbine, trazodone, testosterone and new PDE-5 inhibitors in Phase III clinical trials, such as vardenafil and tadalafil. It is obvious, according to recent data, that the concept of PDE-5 inhibition has a central position in oral pharmacotherapy of ED. However, larger clinical studies of efficacy and safety should be carried out using most of the other above-mentioned oral agents and these may also gain a place in the therapy of ED. There are no studies directly comparing sildenafil and other treatments of ED or assessing its role in combination with other therapies. According to the present knowledge, the quality of life, not only of patients but also of their sexual partners, will be improved significantly with sildenafil usage and this is an important precondition for overall health ofboth. Sildenafil is thus a highly effective peroral treatment for ED in patients without contraindications for its use, which can be considered as the firstline therapy with an acceptable risk-benefit ratio.

Efficacy and safety of sildenafil citrate (Viagra ®) in men with erectile dysfunction and spinal cord injury: a review

Spinal cord injury (SCI) affects a substantial number of men who are young, active, and otherwise healthy. Erectile dysfunction (ED) is a common consequence of SCI. Since its approval, sildenafil citrate (Viagra) has been shown to effectively treat ED of various etiologies. We review the evidence for the efficacy and safety of sildenafil treatment of ED in men with SCI. A literature search identified 2 randomized controlled trials and 4 prospective case series that evaluated sildenafil treatment for ED from SCI. Efficacy was evaluated using an assessment of global efficacy and a more specific assessment of erectile function. For general efficacy, the proportion of patients who reported improved erections and ability to have intercourse was as high as 94%. Up to 72% of intercourse attempts were successful. For measures of erectile function, 5 of the 6 studies showed statistically significant improvements among sildenafil-treated versus placebo-treated patients. Erectile response rates were generally higher in patients with incomplete versus complete SCI and in patients with upper versus lower motor neuron lesions. Nevertheless, a substantial proportion of patients with complete lesions, regardless of level or lower motor neuron lesions, also benefited from sildenafil. Sildenafil was well tolerated. Incidence rates and types of adverse events that occurred in these studies were similar to those published previously. Symptoms of autonomic dysreflexia were not reported in any study. Existing evidence suggests that oral sildenafil is a highly effective and well-tolerated treatment for ED associated with SCI.

Evaluation and Treatment of Erectile Dysfunction in Men With Diabetes Mellitus

Diabetic men have a more than 3-fold increased prevalence of erectile dysfunction (ED) compared with nondiabetic men. Erectile function is primarily a vascular phenomenon, triggered by neurologic controls and facilitated by appropriate hormonal and psychological components. Recent advances in the understanding of the physiology of penile vasculature and its role in male sexual performance have influenced the clinical approach to ED. The pathophysiological alterations leading to impotence in diabetic men include vasculogenic, neurogenic, and hormonal etiologies. A clinical work-up, including a thorough history and physical examination, is an important aspect of ED management. Biochemical evaluations to rule out secondary causes like hypogonadism and thyroid abnormalities are suggested. Oral medications acting through phosphodiesterase inhibition in penile vasculature have revolutionized treatment of impotence in diabetic men. Because of a high success rate in treating ED of various etiologies, these agents are the treatment of choice for most patients. Safety and efficacy of vacuum-constriction devices, intraurethral suppositories, intracavernosal injections, and other therapies are discussed. A clinical algorithm for the evaluation and management of ED is provided for use in the primary care setting.

Management of Erectile Dysfunction

Abstract Erectile dysfunction (ED) affects many men and, as the elderly population grows, the incidence of ED and demand for treatment will increase. Many organic and/or psychogenic factors cause or worsen ED. For healthcare providers and insurers, the treatment of ED involves direct medical costs (e.g. drug costs and physician visits). Indirectly, the effects of ED on the overall health and mental status of the patient may affect medical and societal costs. Management of ED should include alteration of modifiable risk factors (e.g. lifestyle and psychosocial factors); however, these modifications are frequently insufficient to completely reverse ED. Oral sildenafil 25 to 100mg is considered first-line direct therapy for ED and is effective in ≈70% of men with ED. A selective phosphodiesterase type 5 (PDE5) inhibitor, sildenafil improves the ability to attain and maintain erections and increases the rate of successful sexual intercourse in men with ED regardless of their age, presence of other medical conditions and concomitant antihypertensive or antidepressant medications. Sildenafil treatment may be initiated by primary care physicians instead of by specialists, which decreases costs to healthcare payors. Sildenafil treatment significantly improves quality-of-life related to sexual function and general well being; potential healthcare savings may result as these effects trickle down. Commonly reported adverse events are predominantly transient, mild and dose-related and include headache, flushing, dyspepsia, nasal congestion and abnormal vision. Concurrent administration of sildenafil and organic nitrates is contraindicated because marked hypotension may occur. Sublingual apomorphine (not currently available in the US) and vardenafil and tadalafil (PDE5 inhibitors in late stages of development) are other potential oral treatments for ED. Second-line pharmacological therapies include intracavernosal injections (alprostadil, papaverine, phentolamine and combinations of these agents) and intraurethral alprostadil. Non-pharmacological treatments include vacuum constrictor devices and, rarely, vascular surgery or penile implants. In economic models, sildenafil is cost effective compared with no treatment or papaverine/phentolamine injections. The cost-effectiveness of sildenafil compares favorably with that of accepted therapies for other medical conditions. Overall healthcare costs for health plan organizations did not increase significantly with the addition of sildenafil coverage. Seeking medical attention for ED may contribute to the early detection of serious concomitant conditions and result in long-term reductions in healthcare costs. In conclusion, sildenafil is an effective oral therapy for men with ED of various etiologies. Its efficacy in improving erectile function, ease-of-use and good tolerability profile make sildenafil first-line treatment for men with ED who do not have contraindications to its use.

CLINICAL EFFICACY OF SILDENAFIL IN PATIENTS ON CHRONIC DIALYSIS

We evaluate the clinical efficacy of sildenafil citrate for patients who are on chronic dialysis and who have concomitant erectile dysfunction. 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. 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. Sildenafil is an effective and safe treatment for erectile dysfunction in most patients on chronic dialysis.