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PubMed2003

Central mechanisms of erectile dysfunction: what a clinician may want to know.

The interplay between peripheral and central mechanisms of erectile function are not fully elucidated although basic science is moving ahead in this area. It is important from a clinical point of view to understand these mechanisms so that we may begin to make further therapeutic advances in the treatment of erectile dysfunction (ED). It is now widely understood that central disinhibition plays a crucial role in the induction of erectile responses and this has led to the development of the central initiator, apomorphine SL (Ixense ) [apo SL]. Apo SL acts in the paraventricular nucleus of the hypothalamus as a dopamine receptor agonist. It works as a proerectile conditioner at this level to increase the responses of the erectile pathway following appropriate sexual stimulation. This unique central mode of action of apo SL has thus proved efficacious in approximately 70% of ED patients although persistence may be required to produce a robust effect for the maximum number of patients.

Erectile Dysfunction↗

PubMed2006

Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease.

AIMS: Erectile dysfunction (ED) confers an independent cardiovascular risk. We investigated the role of low-grade inflammation and endothelial dysfunction in ED patients with or without coronary artery disease (CAD). METHODS AND RESULTS: We evaluated 141 men (age 58.8 years) for ED and CAD through a rigourous investigation (including coronary angiography to reveal occult CAD). Blood levels of inflammatory (hsCRP, IL-6, IL-1beta, and TNF-alpha) and endothelial-prothrombotic markers/mediators (vWF, tPA, PAI-1, and fibrinogen) were significantly increased in ED patients and correlated negatively with sexual performance. ED was associated with higher levels of these substances (except for IL-6) on top of CAD alone. For most substances, the unfavourable impact of ED alone was not significantly different than the impact of CAD alone. In multivariable models, these markers/mediators predicted independently ED presence. In our population, the negative predictive value of the combination of fibrinogen <225 mg/dL with IL-6 <1.24 pg/mL for excluding ED was 91.7% (95% CI: 61.5-99.8). CONCLUSION: ED is associated with increased inflammatory and endothelial-prothrombotic activation in men with or without CAD. ED confers an incremental unfavourable impact on the circulating levels of these markers/mediators when combined with CAD. These findings have implications for increased cardiovascular risk in ED patients.

Biomarkers↗

PubMed2006

Diabetic erectile dysfunction--an indicator of generalised endothelial function per se?

Erectile dysfunction (ED) affects up to 70% of men with diabetes. However, the pathophysiology of ED in diabetes remains uncertain with both neuronal and vascular factors cited. We examined whether ED is an indicator of generalized endothelial dysfunction. A unique group of diabetic patients free from established conventional cardiac risk factors were investigated. Forearm bloodflow responses to nitroprusside and acetylcholine on 11 diabetic men with ED and 11 potent diabetic men were measured by venous plethysmography. Patient characteristics between the impotent and potent patients were similar except for Hba1c which was higher in the group with ED (8.35% vs. 7.03%: p = 0.003). Both groups showed increases in FBF to incremental infusions of nitroprusside and acetylcholine but the area under curve (AUC) were similar in the ED and the non-ED groups (p = 0.16 and p = 0.17, respectively). We demonstrated that ED in patients with type 2 diabetes is not associated with additional generalized endothelial dysfunction.

Area Under Curve↗

PubMed2003

Erectile dysfunction: cardiovascular risk and the role of the cardiologist.

Erectile dysfunction (ED) shares the same risk factors as coronary artery disease, so the level of occult cardiovascular risk in men with ED was assessed. A total of 174 men presenting with ED underwent cardiac risk stratification according to the Princeton Consensus Guidelines. Thirty per cent were stratified as intermediate/high cardiovascular risk and had ED treatment deferred until further cardiological assessment; 37% had abnormal lipid profiles; 24% had elevated HbA1C/glucose levels; 17% had uncontrolled hypertension; and 6% were suspected of having significant angina. ED is associated with a high incidence of occult cardiovascular disease. We suggest that cardiologists can significantly contribute to the management of ED.

Adult↗

PubMed2005

[Effect of Zhenyangjian on the penile hemodynamics of the patients with arterial erectile dysfunction].

OBJECTIVE: To explore an efficacious therapy for arterial erectile dysfunction (ED) by observing the effect of the Chinese traditional medicine Zhenyangjian on the penile hemodynamics of the patient. METHODS: Forty-seven patients with arterial ED, aged from 40 to 49 years, were treated with Zhenyangjian for 1 month. Intracavernous injection of papaverine and phentolamine (30 mg/l mg) was given and multifunctional color Doppler ultrasound was used to measure the peak systolic velocity(PSV) of the corpus cavernous arteries before and after Zhenyangjian administration. RESULTS: The PSV of the penis corpus cavernous arteries was obviously ameliorated in all the patients (P < 0.05). CONCLUSION: The Chinese traditional medicine Zhenyangjian can promote penile erection effectively.

Adult↗

PubMed2001

Does bicycling contribute to the risk of erectile dysfunction? Results from the Massachusetts Male Aging Study (MMAS).

An association between bicycling and erectile dysfunction (ED) has been described previously, but there are limited data examining this association in a random population of men. Such data would incorporate bicyclists with varied types of riding and other factors. Data from the Massachusetts Male Aging Study (MMAS) were utilized to examine the association between bicycling and ED. Logistic regression was used to test for an association, controlling for age, energy expenditure, smoking, depression and chronic illness. Bicycling less than 3 h per week was not associated with ED and may be somewhat protective. Bicycling 3 h or more per week may be associated with ED. Data revealed that there may be a reduced probability of ED in those who ride less than 3 h per week and ED may be more likely in bikers who ride more than 3 h per week. More population-based research is needed to better define this relationship.

Aging↗

PubMed2005

Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats.

To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.

Animals↗

PubMed2000

[Microsurgical penile revascularization in patients with pure arteriogenic erectile dysfunction].

BACKGROUND: We report the results of microscopic penile revascularization in patients with arteriogenic erectile dysfunction. METHODS: One patient with localized obstruction of the common penile artery underwent the Michal II penile revascularization, 13 patients underwent the Furlow-Fisher procedure, and 5 patients underwent the Hauri procedure. The mean age was 33.0 years and the mean follow-up period was 32 months (4-80 months). Eight patients were tobacco smokers, one patient was over 50 years old. Surgery was considered successful when the patients had a permeable anastomosis and were able to achieve satisfactory erection resulting in normal sexual intercourse. RESULTS: All surgery was successful except for one patient who had undergone the Furlow-Fisher procedure. In Spite of antithrombotic therapy, graft occlusion occurred in two patients. Post operative glans hypervascularity occurred in two patients. CONCLUSION: Penile revascularization surgery is a highly effective treatment for selected patients. There is a need for further study of graft occlusion and glans hypervascularity.

Adult↗

PubMed2003

[Erectile dysfunction in those under 40. Etiological and contributing factors].

OBJECTIVES: Although not very frequent, erectile dysfunction (ED) in patients younger than 40 years represents a disease to be kept in mind in our sanitary area. We propose a study of the various risk factors identified in this population group. METHODS: We studied a total of 736 patients with diagnosis of ED following our protocol, using as inclusion criteria being between 19 and 40 years of age. In this group, we have studied the incidence of various risk factors associated with the disease both globally and dividing the group into age subgroups also. RESULTS: Overall, we have diagnosed 64 patients with ED under the age of 40 years (8.7%). 25 of these patients were classified as psychogenic origin dysfunctions (39%), 26 organic (40.7%), and 13 of mixed origin (20.3%). Age subgroups analysis shows: between 19 and 25 years: 7 psychogenic, 2 mixed, and 5 organic; between 26 and 30: 1 psychogenic, 2 mixed, and 3 organic; between 31 and 35: 7 psychogenic, 3 mixed, and 8 organic; between 36 and 40: 11 psychogenic, 6 mixed, and 9 organic. We identified as risk factors, in order of prevalence: psychogenic (47%), diabetes (14.6%), cardiovascular (9.7%), toxic-alcohol, tobacco, and drugs--(12.1%), neurogenic (4.8%), and others (7.3%). CONCLUSIONS: ED under the age of 40 years causes a growing demand of medical care day by day, mainly due to the increasing prevalence of its etiologic factors. As other publications have shown psychogenic factors are the most frequently associated with the disease in younger patients globally, although when dividing by age groups we found different results than other publications in terms of association with various risk factors.

Adult↗

PubMed2000

New therapies and delivery mechanisms for treatment of erectile dysfunction.

Despite the successes of Viagra, the quest for new and better therapy for erectile dysfunction (ED) continues. In a recent survey of the first 220 patients placed on Viagra at our institution, 101 (46%) quit taking the drug: 76% of those who quit were not satisfied with the results. Patients clearly want an efficacious, safe, convenient medication with rapid onset. To meet these consumer demands, numerous new therapies are being developed. These include new oral medications, new intracavernosal pharmacotherapies, new delivery systems (such as novel intracorporal injectors and transdermal agents) and combination therapies. What is known about these new medications and delivery systems will be presented. Hopefully, from these innovations will come therapies that will improve the overall success and acceptance of treatment for ED. Since it is unlikely that any single agent will ever provide a solution for all men with ED, an expanded armamentarium of treatment options will greatly enhance the chances that any given man will be able to find a therapy that is both acceptable and appropriate to him. International Journal of Impotence Research (2000) 12, Suppl 4, S158-S162.

Administration, Oral↗

PubMed2002

Depression, antidepressant therapies, and erectile dysfunction: clinical trials of sildenafil citrate (Viagra) in treated and untreated patients with depression.

Erectile dysfunction (ED) and depression are highly prevalent conditions and frequently occur concomitantly in predisposed individuals. Men with ED and depression are also likely to have other comorbid conditions, including diabetes, hypertension, and heart disease. Because ED is also a common adverse effect of some medications for these conditions, patients are frequently noncompliant with treatment. Sildenafil citrate (Viagra) is effective in treating ED of a broad range of etiologies, suggesting that it may be equally beneficial in patients with ED that is associated with depressive symptoms and in those with ED resulting from serotonergic reuptake inhibitor (SRI) antidepressant treatment. We review the results of 3 randomized, placebo-controlled trials and a retrospective analysis of data pooled from 10 clinical trials that examine the efficacy of sildenafil in treating ED associated with depression and as an adverse effect of SRI treatment. The results suggest that sildenafil is efficacious as a first-line treatment for ED in men with untreated minor depression, in men with ED that is refractory to successful SRI treatment of depression, and in those whose depression was successfully treated but who developed ED as a consequence of SRI treatment. Given the complex interrelations among ED, depression, and other comorbid conditions, the key to proper management is a comprehensive evaluation, including sexual function, and an accurate differential diagnosis.

Antidepressive Agents, Second-Generation↗

PubMed1996

Pharmacotherapy in erectile dysfunction agents for self-injection programs and alternative application models.

Previously, men with erectile dysfunction (ED) were frequently treated with penile prosthesis implants or considered to have psychogenic impotence. Since the reports by Virag and Brindley in 1932 and 1983, pharmacotherapy, by self-injection programs has become a new therapeutic concept for impotent men. In clinical practice, this application model has been generally accepted as the "golden standard" in the treatment of ED. Papaverine was first used as monotherapy, but because of side-effects such as prolonged erection, priapism, and fibrosis of the corpus cavernosum, single use of the drug was abandoned. Instead, papaverine was introduced in mixtures, e.g. together with alpha adrenoceptor-blockers as phentolamine, and/or prostaglandin E1 (PGE1) in these "cocktails", the dose of papaverine is reduced to 10-15 mg compared to the high doses (80-120 mg) that were used initially. By having two or more drugs in the mixture, a facilitating cascade effect as probably obtained. PGE1 is the only drug that has been approved by the FDA and is today registered in more than 50 countries. Other combination therapies such as vasoactive intestinal polypeptide+ phentolamine, or calcitonin gene-related peptide+ PGE1, have been suggested as suitable alternatives for intracavernosal injection. Transdermal and intraurethral application models may be considered in selected patients. Recently, oral administration of a phosphodiesterase inhibitor (UK-92.480) was reported to improve penile erection in patients with psychogenic impotence. Further clinical results from controlled trials will probably explain if this new oral drug will compete with PGE1 or other agents in self-injection programs.

Erectile Dysfunction↗

PubMed2002

Switching from long-term treatment with self-injections to oral sildenafil in diabetic patients with severe erectile dysfunction.

OBJECTIVE: To assess the efficacy of oral sildenafil in diabetic men with severe erectile dysfunction (ED), who are successfully treated with intracavernous injections of vasoactive drugs. METHODS: 81 impotent diabetic men (29 with type 1 and 52 with type 2) were treated for 1-7 years with self-injections. 13 men were treated with 10 microg and 15 with 20 microg of prostaglandin E1 (PGE1), and 53 with a mixture of PGE1 20 microg and papaverine 7.5-40 mg (MIX). After a 1-week washout period, they changed to oral sildenafil in titrating doses up to 100mg. The change was successful if the man achieved an erection and penetration even once. RESULTS: Sildenafil was discontinued in 23 men because of insufficiency. Eleven men (13.6%), all with type 2 diabetes, responded to sildenafil (10 previously treated with 10 microg and 1 with 20 microg of PGE1, none treated with MIX). Thus, 39.2% of the treated with PGE1 responded to oral sildenafil. The response was influenced by the age, the type of diabetes (type 2) and the kind of the previously injected drug (PGE1 10 microg); it was not influenced by the duration of diabetes, ED and treatment with self-injections. CONCLUSIONS: Despite the well documented efficacy of sildenafil, self-injections continue to be the solely effective therapeutic modality in many diabetic men afflicted by severe ED. Only the younger men with non-insulin-dependent diabetes, treated with low doses of PGE1 are more likely to respond to oral sildenafil and change treatment. Men with insulin-dependent diabetes or treated with mixtures of vasoactive drugs are not likely to respond to oral sildenafil.

Administration, Oral↗

PubMed2025

Plasma metabolites mediate the causal relationship between gut microbiota and erectile dysfunction: insights from Mendelian randomization study.

BACKGROUND: While the relationship between gut microbiota and erectile dysfunction (ED) has been reported, the specific pathways involved remain unclear. AIM: This study aims to investigate the causal relationship between gut microbiota and ED, and to identify the potential role of plasma metabolites as mediators. METHODS: Utilizing aggregated genome-wide association study (GWAS) data, a comprehensive two-sample Mendelian randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1400 plasma metabolites and ED. Causal relationships between gut microbiota, plasma metabolites and ED were explored. In addition, mediation analysis was applied to identify the pathway from gut microbiota to ED mediated by plasma metabolites. OUTCOMES: This study reveals that plasma metabolites act as mediators regulating the influence of gut microbiota on ED. RESULTS: MR analysis identified causal relationships between six gut microbial taxa and ED, with Butyrivibrio increasing the risk of ED, while Alistipes, Prevotella 9, Dialister, Marvinbryantia, and LachnospiraceaeUCG010 exhibited protective effects. Additionally, 45 plasma metabolites demonstrated causal associations with ED. Finally, mediation analysis revealed four mediation relationships. Sensitivity analysis indicated no heterogeneity or pleiotropy in this study. CLINICAL IMPLICATIONS: Modulating gut microbiota or targeting specific metabolites may offer new therapeutic approaches for ED, highlighting the potential for microbiome-based interventions. STRENGTHS AND LIMITATIONS: The MR approach and large-scale GWAS data provide robust causal evidence, but the findings are limited by their focus on European populations and lack of experimental validation. Further studies are needed to confirm these mechanisms in diverse cohorts and functional models. CONCLUSION: This study establishes a causal link between gut microbiota, plasma metabolites, and ED, identifying specific microbial taxa and metabolites as key contributors to ED risk. The mediating role of plasma metabolites highlights potential therapeutic strategies, such as probiotics or dietary interventions targeting harmful metabolites.

Mendelian randomization↗

PubMed2005

Association between erectile dysfunction and sleep disorders measured by self-assessment questionnaires in adult men.

BACKGROUND: Erectile dysfunction (ED) is often associated with sleep disorders and sleep apnea syndrome (SAS) in mostly middle-aged and elderly men. Sleep disorders and ED are also prevalent in younger men. PURPOSE: To study the association between ED, sleep disorders, and SAS, particularly among adult men. METHODS: A health screening program is offered by the Israel Defense Force (IDF) for career servicemen older than 25 years, for the purpose of early detection of ED and sleep disorders, among other concealed morbidities. The Sexual Health Inventory for Man questionnaire (SHIM) was used to measure ED. The Sleep Quality (SQ) questionnaire, developed by the medical services of the IDF, was used to characterize SAS and other sleep disorders. RESULTS: From 2002 through 2003, 3,363 men (mean age, 36.1+/-6.8 years) replied to the SHIM and SQ questionnaires. Of these men, 337 (10%) scored high (>or=25) in the SQ questionnaire, suggesting moderate to severe sleep disorders, and 870 men (25.8%) scored low (<or=21) in the SHIM questionnaire, suggesting ED. There was a negative correlation between the scores in the SHIM questionnaire and in the SQ questionnaire (r=-0.29, P<0.0001)-even after age adjustment and after excluding men with risk factors for both ED and SAS (such as essential hypertension, diabetes mellitus, and obesity; r=-0.21, P<0.0001). This correlation was consistent with all severity levels of ED and sleep disorders. CONCLUSIONS: Sleep disorders, in particular SAS, and ED are prevalent and may be related in adult men. Either ED or sleep disorders should be considered whenever the other is suspected in adult men. Sleep disorders and ED should also be investigated for the purpose of treating underlying systemic diseases and emotional disorders, and in order to prevent late complications of atherosclerosis.

Adult↗

PubMed2004

Vardenafil: a new oral treatment for erectile dysfunction.

Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in the USA in late 2003. It is a potent and selective inhibitor of the enzyme phosphodiesterase type 5, and in the presence of an erectile stimulus potentiates the intracellular actions of cyclic guanylate monophosphate. Several large, placebo-controlled trials have demonstrated efficacy both in the broad population of men with ED and in men with more difficult to treat ED. It is well tolerated with a side effect profile typical of this class of drugs. It has a rapid onset of action and has demonstrable efficacy for men using the medication for up to 2 years.

Clinical Trials as Topic↗

PubMed2000

Near infrared spectrophotometry for the diagnosis of vasculogenic erectile dysfunction.

A specialized near infrared spectrophotometry instrument for noninvasive, continuous monitoring of the hemodynamic events of erection in the human penis has been developed. Its potential application for the diagnostic evaluation of erectile dysfunction was investigated. Thirty-eight patients and 18 volunteer subjects underwent penile near infrared spectrophotometry using an optical sensor probe with wavelength selectivity for hemoglobin absorption spectra. Penile blood volume changes and their time courses were measured following intracavernous pharmacostimulation in patients and visual sexual stimulation in volunteers. Spectrophotometric results were compared with results obtained simultaneously using color duplex ultrasonography, strain gauge penile circumference monitoring, penile tonometry, and clinical assessments. Spectrophotometric recordings of penile erection showed measurable blood volume changes consistent with the hemodynamic events of this biological function. Blood volume per cent (BV%) increase correlated with clinical ratings of erection quality (P < 0.001), penile rigidity measurements (P < 0.005), and penile circumference increases (P < 0.0001), and it correlated with mean peak systolic velocity measurements when BV% increase was restricted to values less than 50% (P < 0.001). The time to reach half the maximum blood volume change (BV T1) correlated directly with the time to reach half the maximum penile circumference size increase (P < 0.001), whereas BV T4 correlated inversely with mean resistive index measurements only when BV T(1/2) was restricted to values greater than 120 s (P < 0.05). Spectrophotometric criteria consisting of BV % less than 35% and BV T(1/2) greater than 120 s affirmed the diagnosis of severe erectile impairment with a similar degree of accuracy as standard ultrasonographic criteria (P < 0.002). Penile near infrared spectrophotometry is a safe, inexpensive and simply used biomedical optics technique that provides quantitative measurements of the vascular physiology of penile erection and appears to offer clinical utility in the diagnosis of vasculogenic erectile dysfunction.

Adult↗

PubMed1991

Psychological treatment of erectile dysfunction in men without partners: outcome results and a new direction.

Studies concerning the psychological treatment of erectile dysfunction in men without partners are reviewed. A significant majority of single men experience improved erectile functioning following surrogate-assisted or men's group therapy. However, the expense and unresolved legal status of surrogate therapy and logistical problems in forming men's groups limit the availability of these treatments. "Personal Potential" is a new audio cassette adjunct for individual therapy. To approximate a men's group experience, "Personal Potential" includes discussions by former clients, didactic presentations, communication roleplays, and sexual and social homework assignments. Routine attention to communication problems in men without partners may also increase patient satisfaction with intracavernosal vasodilator self-infections, penile implants, or vacuum constriction devices.

Combined Modality Therapy↗