Effective Treatment For Erectile Dysfunction Research Articles

Penile prosthesis implantation: past, present and future

Penile prosthesis implantation is the oldest effective treatment for erectile dysfunction. This review examines the past, present and future of penile prosthesis implantation. Advances in prosthetic design and implantation techniques have resulted today in devices that produce nearly normal flaccid and erect states, and have remarkable freedom from mechanical failure. The future of prosthetic design holds promises for even more improvements.

The Penile Erection Efficacy of a New Phosphodiesterase Type 5 Inhibitor, Mirodenafil (SK3530), in Rabbits with Acute Spinal Cord Injury

Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury.

Injection therapy for the treatment of erectile dysfunction: a comparison between alprostadil and a combination of vasoactive intestinal polypeptide and phentolamine mesilate

ABSTRACTObjective: To compare two injectable treatments, alprostadil 5–20 µg powder for injection and a combination of vasoactive intestinal polypeptide (VIP) and phentolamine in patients with erectile dysfunction (ED).Design and methods: This was an open multicentre, randomised crossover study comprising two phases. The first phase established the dose of each drug required to produce an erection suitable for sexual intercourse (grade 3 erection). In phase 2, responders to both drugs received, in random order, four doses of VIP/phentolamine, presented as ampoules, and four doses of alprostadil, presented as powder for injection. This was followed by four doses of VIP/phentolamine, presented in an autoinjector. In both phases, patient preference was assessed for each preparation.Results: 187 patients were recruited. In the first phase, both treatments were effective, (83% alprostadil vs. 73% VIP/phentolamine, p = 0.002) but more patients preferred VIP/phentolamine (69 vs. 31%, p = 0.011). In phase 2 (n = 107), the proportion of injections that produced a grade 3 erection was similar for all three treatments (83–85%), but both presentations of VIP/phentolamine (ampoule and auto-injector) were preferred by significantly more patients ( p < 0.001). Compared with both presentations of VIP/phentolamine, alprostadil produced a higher frequency of pain (28% of injections vs. 3% for each VIP/phentolamine presentation; p < 0.001) and a lower frequency of facial flushing (3 vs. 16–17%; p < 0.001).Conclusions: VIP/phentolamine and alprostadil were effective treatments for ED, however the VIP/phentolamine combination was preferred by more patients, which may be because it was much less likely to cause pain.

Sildenafil citrate in the treatment of sexual dysfunction and its effect on quality of life in alcohol dependent men: preliminary findings

Alcohol-dependent men commonly suffer from erectile dysfunction (ED) and men with ED are frequently chronic alcohol addicts. Sildenafil is used for treatment of ED caused by diverse factors. The aim of this study was to examine (i) the effect of sildenafil citrate (VIAGRA) on ED in alcohol dependent men, and (ii) whether the effective treatment of ED with sildenafil improves the patient's QoL and related emotional distress. Fifty-four men with an ICD-10 diagnosis of alcohol dependence (AD) and concomitant ED agreed to enter an open-label trial, in which they were assigned to take 50 mg of sildenafil as add-on to a standard treatment for AD for 12 weeks. Fifty patients (92.3%) completed all baseline and endpoint assessments. Efficacy was evaluated using the International Index of Erectile Function (IIEF), Quality of Life Enjoyment and Satisfaction Questionnaire and General Health Questionnaire. At endpoint, total IIEF scores had improved significantly (Delta=16.9), reflecting a 42% improvement (P<0.0001). A significant increase in the mean scores of each sexual function domain was also noted among all subjects. Sildenafil's positive effect was accompanied by a significant improvement (P<0.001) in satisfaction with overall QoL and specific life-domains, as well as a significant reduction in emotional distress scores (P<0.001). The sildenafil add-on evaluated in this trial had a marked beneficial effect on ED and QoL, and was associated with a significant reduction in emotional distress among men with AD. The information obtained is valuable for both clinicians and policymakers in developing innovative therapeutic strategies for men with AD.

Sildenafil citrate: a safe and effective treatment for erectile dysfunction after renal transplantation?

Sildenafil citrate: a safe and effective treatment for erectile dysfunction after renal transplantation?

Treating Erectile Dysfunction in Renal Transplant Recipients

Erectile dysfunction is common in male kidney transplant recipients. Interference with the physiology of erections can be attributed to recipient co-morbidities, the renal transplant operation, medication adverse effects, relationship problems and changes in mental health. A treatment-oriented evaluation of erectile dysfunction allows the development of treatment plans that are patient-specific. Hypo-gonadal men whose hormone parameters do not improve after renal transplantation may respond to testosterone replacement therapy. Use of recommended doses of the phosphodiesterase-5 inhibitor sildenafil does not significantly modify trough concentrations of the calcineurin inhibitors ciclosporin and tacrolimus or result in impaired renal allograft function. Tacrolimus has been shown to increase the peak concentration and prolong the elimination half-life of sildenafil in kidney transplant recipients. Daily administration of sildenafil has resulted in decreased blood pressure in kidney transplant recipients with treated hypertension and tacrolimus immunosuppression. Intracavernosal injections of alprostadil, with or without papaverine and phentolamine, are effective treatments for erectile dysfunction after renal transplantation and have not resulted in alterations of ciclosporin concentrations or in deterioration of renal function. Penile prostheses can be successfully implanted after pelvic organ transplantation without significant risk of infection.

66: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study to Assess the Efficacy of Tadalafil (Cialis®) in the Treatment of Erectile Dysfunction Following Three-Dimensional Conformal External-Beam Radiotherapy for Prostatic Carcinoma

Prostatic carcinoma has become the most frequent non-skin male malignancy in Western countries. Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in up to 64% of the patients carcinoma. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis®) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. 358 patients who completed radiotherapy at least 12 months prior to the study were approached by mail. All patients had been treated by 3DCRT. Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebo for 6 weeks. At 6 weeks patients crossed over to the alternative treatment. Drug or placebo was taken on demand at patient’s discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side-effects were also recorded, using a patient-completed standardized form, after each treatment period. Comparison between tadalafil scores and placebo scores was done using Wilcoxon’s matched pairs test. For within- and between-group comparison of percentages, McNemar’s test and Fisher’s exact test were used, respectively. Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. For all the IIEF domains there was a statistically significant difference between tadalafil and placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%) and 48% reported successful intercourse with tadalafil (placebo: 9%) (p<0.0001). Side effects were mild or moderate. Except for headache, flushing and dyspepsia, all other reported adverse events did not differ significantly between the two treatments (tadalafil or placebo). No patient decreased the dose to 10 mg. Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and is well tolerated.

A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis ®) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma

Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. Patients (N=358) who completed radiotherapy at least 12 months before the study were approached by mail. All patients had been treated by 3DCRT; 60 patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebo for 6 weeks. Drug or placebo was taken on demand at patient's discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. At 6 weeks patients crossed over to the alternative treatment. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side effects were also recorded. Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil (placebo: 9%) (p<0.0001). Side effects were mild or moderate. Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and it is well tolerated.

Topical alprostadil cream is an effective treatment for erectile dysfunction,

Topical alprostadil cream is an effective treatment for erectile dysfunction,

Effectiveness of Sildenafil in Treating Erectile Dysfunction in PTSD Patients

Post Traumatic Stress Disorder (PTSD) is known to be associated with Erectile Dysfunction (ED). Sildenafil citrate was shown to be effective treatment for ED among different clinical populations. However, to date, no placebo-controlled trial has assessed sildenafil's effectiveness for treating ED in PTSD patients. The goal of the present study was to address this question using a double-blind placebo controlled crossover design. A four-week double-blind crossover trial of sildenafil (50 mg up to 100 mg per usage) versus placebo was conducted on 21 outpatients diagnosed with chronic PTSD accompanied by ED. Erectile function was assessed biweekly using the International Inventory of Erectile Function (IIEF). Depressive symptoms, PTSD symptoms and subjective well-being scores were assessed as well. Analysis of IIEF scores revealed a main effect of treatment phase (E = 33.361, df =2, P < 0.000). Pairwise comparisons showed that sildenafil IIEF scores (mean = 45.19 +/- 15.05) were significantly higher compared to baseline scores (mean = 20.00 +/- 12.32, P = 0.000) and placebo scores (mean = 33.04 +/- 12.99). Compared to placebo, a significant improvement was also observed during the sildenafil phase in erectile function, orgasmic function and sexual desire. There was no significant change in depression, PTSD symptoms or subjective well-being. The results of this study suggest that sildenafil citrate treatment for ED in PTSD patients was accompanied with improvement of ED symptoms and was found to be significantly better than placebo. Nevertheless, this effect should be considered marginal since patients still meet the criteria of ED after treatment. Larger, parallel group studies are warranted.

Phosphodiesterase-5 inhibitors and their hemodynamic effects

Erectile dysfunction occurs commonly in untreated and treated hypertensive patients, impairing adherence to treatment and quality of life. Furthermore, it is a marker for enhanced risk for cardiovascular disease. Phosphodiesterase type 5 (PDE5) inhibitors, sildenafil, vardenafil, and tadalafil, provide effective treatment of erectile dysfunction. They reduce blood pressure in healthy patients: sildenafil 100 mg, -3.7/-3.6 mm Hg; vardenafil 20 mg, -7.5/-8 mm Hg; and tadalafil 20 mg, -1.6/-0.8 mm Hg. Greater declines in blood pressure with a PDE5 inhibitor may be observed in treated and untreated hypertensive patients. The additive effect of PDE5 inhibitors with one or multiple antihypertensive drugs is modest. alpha(1)-Blockers, except tamsulosin, may result in larger declines in blood pressure and cause orthostatic hypotension. Thus, caution should be exercised by using the lowest doses of proportional, variant(1)-blockers and PDE5 inhibitors in combination. Nitrates in combination with PDE5 inhibitors cause a profound decline in blood pressure and are contraindicated.

ORIGINAL RESEARCH—COUPLES’ SEXUAL DYSFUNCTIONS: Women's Sexual Function Improves When Partners Are Administered Vardenafil for Erectile Dysfunction: A Prospective, Randomized, Double‐Blind, Placebo‐Controlled Trial

ABSTRACT Introduction There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED). Aim One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners’ sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment. Methods A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED &amp;gt;6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner). Main Outcome Measures Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI). Results Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners’ FSFI total and individual domain scores. Conclusions Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners’ sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.

Sildenafil, Tadalafil, and Vardenafil Are Equally Effective Treatments for Erectile Dysfunction After Bilateral Nerve Sparing Prostatectomy

Since the introduction of sildenafil in late 90’s, the treatment algorithm for erectile dysfunction (ED) following radical prostatectomy (RP) has changed rapidly and oral agents have become the first line agents. The role of sildenafil has been widely investigated since the landmark study by Goldstein et al in 1998. Vardenafil and tadalafil are two recently introduced PDE-5 inhibitors who are reported to be effective in the treatment of ED following RP. However, no one has compared the efficacy of individual drugs in the same population. Our objective was to compare the therapeutic efficacy of tadalafil and vardenafil, in patients successfully responding to sildenafil for the treatment of ED after bilateral nerve sparing RP. Prospective study. In this prospective cross over study, we included 46 men with ED following bilateral nerve sparing RP who previously responded to 100mg of sildenafil. The baseline (without any treatment) and sildenafil SHIM scores (abridged version of International Index of Erectile Function) were collected for all patients. Patients were given 20mg tadalafil for 5 weeks, then 20mg vardenafil for 5 weeks. All patients had a one-week washout period between drugs and the sequence of drug use was random. All patients completed the Sexual Health Inventory of Men (SHIM) questionnaire, the Cleveland Clinic Foundation Rigidity (CCFR) Score, and a side-effect profile after each drug. CCFR was graded on the visual analogue scale of 1-100 (1 = 0-20, 2 = 30-40, 3 = 50-60, 4 = 70-80, 5 = 90-100.) Thirty-nine patients (39/46) completed a 5 week trial of each PDE-5 inhibitor, 5 patients discontinued due to side effects, and 2 patients lost to follow-up. The mean SHIM score for sildenafil was 18.2 ± 1.26, tadalafil 17.6 ± 1.4, and vardenafil 17.9 ± 1.9. Mean CCF Rigidity score (0-5) for sildenafil was 3.8 ± 0.9, tadalafil 3.1 ± 0.7, and vardenafil 3.3 ± 0.8. Patients with pre-treatment (baseline) SHIM scores < 10 preferred sildenafil, while >10 patients preferred tadalafil. Of the 46 patients, 23 (50%) still preferred sildenafil, 14 (30%) preferred tadalafil, and 9 (20%) preferred vardenafil. Most frequent side effects reported with sildenafil were headaches (n = 4), flushing (n = 3) and visual disturbances (n = 1). Most frequent side effects with tadalafil were backache (n = 5), headache (n = 3) and flushing (n = 1). Headache (n = 6) and flushing were the two most common side effects with vardenafil. None of the patients discontinued sildenafil due to side effects, while three patients discontinued tadalafil due to backache and two discontinued vardenafil due to headaches. Sildenafil, tadalafil, and vardenafil, are equally effective treatments in patients with erectile dysfunction after nerve sparing radical prostatectomy.

TREATMENT OF ERECTILE DYSFUNCTION FOLLOWING THERAPY FOR CLINICALLY LOCALIZED PROSTATE CANCER: PATIENT REPORTED USE AND OUTCOMES FROM THE SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS PROSTATE CANCER OUTCOMES STUDY

Erectile dysfunction (ED) persists for years following curative therapies for clinically localized prostate cancer. We report use and treatment outcomes in a 5-year interval in a population based cohort from the Surveillance, Epidemiology, and End Results Prostate Cancer Outcomes Study. A sample of 1,977 men with localized prostate cancer who received external beam radiation therapy or radical prostatectomy in 1994 to 1995 were surveyed for 5 outcome measures of ED treatment, namely treatment, perceived helpfulness, erectile sufficiency, sexual activity frequency and erection maintenance. Subjects were surveyed 6, 12, 24 and 60 months after prostate cancer diagnosis. Overall 50.5% of men ever used ED treatment. The use of ED treatments increased during the study course. Subject age, regular sexual partner and baseline sexual activity were factors positively associated with ED treatments. While it was used uncommonly (1.9%), a penile prosthesis was perceived as the most helpful ED treatment (helped a lot in 52% of respondents). Sildenafil helped a lot in 12% of respondents. Erectile fullness, erection maintenance and sexual activity frequency were modestly improved in men using ED treatment compared with those in men not using ED treatment. Approximately half of the patients in this population based cohort of men used ED treatment during the 5 years following prostate cancer diagnosis. Men using ED treatments had modest improvement in sexual function compared with men that in who did not receive ED treatment at 60 months. More effective treatments for ED following local therapy for prostate cancer are needed.

Improvement of sexual function in partial testosterone-deficient ageing men treated with cream containing testosterone and vasoactive agents

Background Erectile dysfunction has multiple causes in older men. Combination therapy may therefore be an attractive option. Methods We conducted a randomized double blind trial over 2 months. We allocated 89 men who had different causes of erectile dysfunction and low testosterone concentrations randomly to two groups. One group received topical therapy with placebo cream and the other received active cream containing testosterone 0.8%, isosorbide dinitrate 0.5% and co-dergocrine mesylate 0.06%. Serum concentrations of total testosterone were measured every 15 days. Response to each therapy was assessed by measurement of tumescence using RigiScan and a sexual questionnaire. Results Serum concentrations of total testosterone increased significantly in all patients ( p < 0.05) after 15 days of treatment with active cream (240 ± 27 ng/dl vs. 360 ± 29 ng/dl). Application of active cream to the penile shaft in the laboratory induced full tumescence in 18% of patients and partial tumescence in 53%. No patient had full tumescence after application of placebo cream. Sexual desire was improved in 70% of patients during treatment with active cream. Analysis of data from the questionnaires showed that 40% of patients reported full erections with successful intercourse, sexual enjoyment and satisfaction and 37% reported partial erections that were insufficient for successful intercourse. No patient experienced a full erection and successful intercourse after placebo cream. No major side effects were reported. Conclusion Topical treatment with cream containing testosterone and vasoactive agents is a new effective treatment for erectile dysfunction associated with low testosterone concentrations, particularly for patients with psychogenic causes.

Erectile Dysfunction: Pathophysiologic Mechanisms Pointing to Underlying Cardiovascular Disease

Evidence exists that erectile dysfunction (ED) is analogous to endothelial dysfunction, a known precursor to atherosclerosis in terms of molecular mechanisms and underlying risk factors. These findings are discussed, along with the biologic underpinnings for the clinical observation that ED is an "early warning system" for atherosclerosis. Molecular mechanisms of ED as potential targets of novel therapies are considered, as well as the role of phosphodiesterase 5 inhibitors--currently the most effective treatment of ED--as promising therapies of cardiovascular diseases characterized by endothelial dysfunction.

Endothelial dysfunction links erectile dysfunction to heart disease

Erectile dysfunction (ED) and coronary artery disease (CAD) overlap in risk factors, aetiology and clinical outcomes. It has become clear that ED is an important marker of vascular disease throughout the arterial tree--including CAD, stroke and diabetes. Epidemiological studies have demonstrated a close association between ED and vascular disease. The shared aetiological factor is endothelial dysfunction. The fact that ED tends to precede the onset of symptoms of other vascular diseases--because blood vessels in the penis are narrower in diameter than elsewhere in the body so blood flow is restricted sooner by atherosclerosis--means that it can be used as a 'window' on vascular health. There is growing evidence that patients presenting with ED should be investigated for cardiovascular disease (CVD), including diabetes, even if they have no symptoms. Early detection could facilitate prompt intervention and a reduction in long-term complications. Treatments that reduce endothelial dysfunction offer the potential of improving the functioning of the entire vascular system, improving outcomes in CVD and diabetes, as well as providing effective treatment for ED.

Aetiology and Management of Male Erectile Dysfunction and Female Sexual Dysfunction in Patients with Cardiovascular Disease

The historical basis for understanding erectile function as a neurovascular phenomenon and the advance from fanciful to effective treatment of erectile dysfunction (ED) are reviewed, with emphasis on patients with cardiovascular disease (CVD). ED occurs in 60% of CVD patients by 40 years of age. Male ED and female sexual dysfunction (FSD) diminish quality of life and often warn of occult CVD. ED is often unrecognised but is readily diagnosed during a 5-minute interview using a truncated International Index of Erectile Function questionnaire. Erection of the penis and clitoral engorgement result from local, arousal-induced release of neuronal and endothelial-derived nitric oxide (NO). Arterial vasodilatation and relaxation of cavernosal smooth muscle cells cause arterial blood to flood trabecular spaces, compressing venous drainage, resulting in tumescence. Cyclic guanosine monophosphate (cGMP)-induced activation of protein kinase G mediates the effects of NO by enhancing calcium sequestration and activating large-conductance, calcium-sensitive K+ channels. Future treatment strategies will likely enhance these pathways. Phosphodiesterase-5 inhibitors (sildenafil, tadalafil and vardenafil) increase cGMP levels in erectile tissue. These agents are effective in 80% of CVD patients with ED and can be used safely, even in the presence of stable coronary disease or congestive heart failure, provided nitrates are avoided and patients do not have hypotension, severe aortic stenosis or evocable myocardial ischaemia. Second-line therapies (vacuum constrictor device and transurethral or intracavernosal prostaglandin E1) can also be used in CVD patients. Treatment of FSD and its relationship to CVD are less well established, but similarities to ED exist. ED can be prevented by reduction of CVD risk factors, exercise, weight loss and abstinence from smoking.

Pharmacotherapy for Erectile Dysfunction

Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction. To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction. An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries. Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation. There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

Oral sildenafil in the treatment of erectile dysfunction in diabetic men: A randomized double-blind and placebo-controlled study

Purpose: To determine the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction (ED) in diabetic men. Materials and methods: In a randomized, double-blind, placebo-controlled, and fixed-dose study, a total of 282 men (mean age, 46.4 years) with ED (mean duration, 3.6 years) and diabetes (mean duration, 11 years) were randomly assigned to receive 100 mg sildenafil ( n=144) or placebo ( n=138) approximately 1 h before planned sexual activity, but not more than once daily, for 16 weeks. The efficacy of two treatments was assessed using responses to the International Index of Erectile Function (IIEF) questionnaire. Results: Two hundred sixty-two (93%) of men completed the study (134/144 in the sildenafil group, 128/138 in the placebo group). Positive clinical results were obtained in 68 (51%) of 134 patients in the sildenafil group compared with 14 (11%) of 128 patients in the placebo group ( P<.003). Fifty-nine percent of the patients reported at least one successful attempt at sexual intercourse in the sildenafil group as compared with 21% successful attempts for the placebo group ( P<.002). Drug-related adverse effects occurred in 32 (22%) of 144 patients taking sildenafil and 4 (3%) of 138 patients receiving placebo. The most common adverse events were headache (20% sildenafil, 2% placebo), flushing (19% sildenafil, 0% placebo), dyspnea (9% sildenafil, 2% placebo), rhinitis (6% sildenafil, 0% placebo), and cardiovascular effects (7% sildenafil, 0% placebo). Of patients taking sildenafil, four (2.7%) developed new chest pains, with documented myocardial infarction in two. Conclusion: Oral sildenafil is a moderately effective treatment for ED in men with diabetes. The response rate was lower and cardiovascular events were higher than previously reported in nondiabetic patients.