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Structured interview on erectile dysfunction (SIEDY): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction.

The aim of the present study is the definition of a brief structured interview (SI) providing scores useful for identification and quantification of pathogenetic factors of erectile dysfunction (ED). A SI was developed and applied to a consecutive series of 320 ED patients. A 13-item SI, with three-factor analysis-derived scales, was identified and applied for validation to an independent consecutive series of 194 ED patients. PGE(1) (10 microg) intracavernosal injection, penile duplex ultrasound (PDU), blood hormones, PSA, glycemia, and lipids were used for the assessment of an organic component (OC), and Middlesex Hospital Questionnaire (MHQ) modified for psychological disturbances. Scale 1, dealing with OC, showed a positive correlation with age, BMI, blood pressure, glycemia, and inverse correlation, with testosterone, PGE(1) and several parameters derived from PDU. Scale 2, related to partner's relationship, was not correlated with organic parameters. Scale 3, which measures psychopathological traits was correlated with MHQ scales. Scale 1 (>3) had a sensitivity of 67.9% and a specificity of 67.6% for OC. SIEDY((c)) provides information on ED pathogenesis and might assist physicians in diagnostic and therapeutic choices.

Adult↗

Cardiovascular disease, metabolic syndrome and erectile dysfunction.

PURPOSE OF REVIEW: Erectile dysfunction and cardiovascular disease share the same risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking, all of which are implicated in causing endothelial dysfunction. In this review, an overview is given on the role of endothelium in the pathophysiology of erectile dysfunction, cardiovascular disease, and the metabolic syndrome as well as the links between them. RECENT FINDINGS: Current literature offers strong evidence that endothelial dysfunction and erectile dysfunction are linked. Erectile dysfunction appears to be one of the earliest signs of systemic vascular disease and might be considered as an early marker for subclinical cardiovascular disease. Obesity is one of the many risk factors for cardiovascular disease and is also associated with hypertension, dyslipidemia, glucose intolerance, and insulin resistance, which together define the metabolic syndrome. Experimental, clinical, and epidemiologic studies support the association between metabolic syndrome and cardiovascular disease. SUMMARY: The above-mentioned risk factors are a potential threat to the penile endothelium and the smooth muscle tissue leading to functional and structural changes. These important pathophysiologic factors are the foundation for the strong link between erectile dysfunction and cardiovascular disease. Recent literature supports the link between metabolic syndrome and erectile dysfunction and highlights metabolic syndrome as a potential risk factor for the development of erectile dysfunction.

Cardiovascular Diseases↗

Intracavernosal injection therapy. Does it still have a role in erectile dysfunction?

BACKGROUND: Male erectile dysfunction (ED) is a common problem in the community. It may go unnoticed unless specific questions are asked. The range of management options has increased markedly over the past two decades. OBJECTIVE: This article revisits the option of intracavernosal injection therapy for male erectile dysfunction. DISCUSSION: Erectile dysfunction has attracted considerable interest and research. The recent availability of an orally effective medication (sildenafil) has brought about a paradigm shift in its management.

Adult↗

Erectile dysfunction: an overview.

Erectile dysfunction is a common (affecting 10-20 million men in the USA) and multifactorial disease due to organic and/or psychological factors that strongly impairs the quality of life in man. During the past decade many advances in the understanding of the pathophysiology of erectile dysfunction have been made and new therapeutic strategies have become available. It has been established that an insufficient production of nitric oxide by penile nerve terminals and/or vascular endothelium may result in an impaired erection or complete impotence. Nowadays, intracavernous injection of vasoactive drugs represents a standardized approach for the diagnosis, and the treatment of choice, for erectile dysfunction, but is not widely accepted by the patients. The possibility of treating erectile dysfunction with intraurethral administration of prostaglandin-E1 has recently become available in the USA, and is a therapy more acceptable to the patients. Other noninvasive medical therapies are undergoing evaluation.

Erectile Dysfunction↗

Association between the Erectile Dysfunction Inventory of Treatment Satisfaction and the Self-Esteem and Relationship Questionnaire following treatment with sildenafil citrate for men with erectile dysfunction.

OBJECTIVES: Research is lacking on the correlation between treatment satisfaction and confidence, self-esteem, and relationships for men receiving treatment for erectile dysfunction (ED). We sought to correlate scores between the validated Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index and the validated Self-Esteem And Relationship (SEAR) questionnaire following treatment with sildenafil citrate (VIAGRA). METHODS: This study was based on an open-label, flexible-dose trial of 93 sildenafil-naive patients with ED. Pearson correlation coefficients between EDITS index and SEAR questionnaire scores, each of which can range from 0 to 100 (most favorable), were calculated at end of treatment (EOT). An analysis of covariance model was applied to associate changes from baseline to EOT in SEAR scores with EDITS score at EOT, controlling for baseline SEAR score. RESULTS: Significant and sizable Pearson's correlations between SEAR and EDITS scores (P < or = 0.0001; range: 0.49-0.84) were observed. A 10-point higher EDITS scores at EOT corresponded to a significant and tangible average improvement in SEAR scores from baseline to EOT (P < or = 0.0001; range: 6.6-8.7). Average SEAR scores at EOT were markedly different between patients with greater treatment satisfaction at EOT (EDITS score > or = median EDITS score of 88.6; n = 50) and those with lesser treatment satisfaction at EOT (EDITS score <88.6; n = 43). CONCLUSIONS: The data add to the validity of the SEAR questionnaire, suggest a tangible relationship between treatment satisfaction and psychosocial benefit among men with ED treated with sildenafil, and highlight the importance of assessing the psychosocial impact of ED in men undergoing treatment.

Adult↗

The anatomy, physiology and molecular pathways of vascular erectile dysfunction.

Vascular erectile dysfunction (VED) is composed of penile arterial insufficiency and veno-occlusive dysfunction. Both the arterial and venous dysfunctions are associated with cellular and molecular abnormalities. The goal of this work is to provide a summary of the gross anatomical and physiological abnormalities associated with VED and a theory of how these abnormalities result in VED based on the known molecular mechanism in cavernosal tissue and non-penile vascular tissue.

Angiotensin II↗

Relationship between testosterone and erectile dysfunction.

Although erectile function is clearly androgen dependent, is it just as clear at what level of testosterone erectile dysfunction (ED) begins? Does the decline in testosterone that occurs with aging always produce ED? Are exogenous androgens the answer to ED? The answers range from clear to complex.

Journal Article↗

Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response.

OBJECTIVES: To evaluate the safety and pharmacodynamic effect of co-administration of subtherapeutic doses of PT-141, a cyclic heptapeptide melanocortin analogue, and sildenafil to patients with erectile dysfunction. METHODS: Nineteen patients with erectile dysfunction who were responders to either Viagra or Levitra by self-report were given 25 mg sildenafil and 7.5 mg intranasal PT-141, 25 mg sildenafil and an intranasal placebo spray, and a placebo tablet and an intranasal placebo spray in a randomized cross-over design. Erectile activity in response to two 30-minute episodes of visual sexual stimulation was assessed by RigiScan during a 6-hour postdose period. RESULTS: The erectile response induced by co-administration of PT-141 and sildenafil was significantly greater than the response elicited by administration of sildenafil alone. Co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy. CONCLUSIONS: Co-administration of intranasal PT-141 and a phosphodiesterase type 5 inhibitor may constitute a treatment alternative for patients in whom higher doses of a single therapy are not effective or well tolerated.

Administration, Intranasal↗

Doppler evaluation of erectile dysfunction - part 1.

Erectile dysfunction (ED) is the consistent inability to achieve and maintain an erection sufficient for satisfactory sexual activity. Erectile dysfunction affects as many as 30 million men in America, with an increasing prevalence with age. Erectile dysfunction is secondary to organic, psychogenic and combined causes. The first part of this review article describes the guidelines for evaluation and treatment plans for men with ED. It also describes the normal sonographic anatomy of the penis, sonographic technique for evaluation of ED and the normal phases of erection.

Adult↗

Lack of central nitric oxide triggers erectile dysfunction in diabetes.

Erectile dysfunction is a serious and common complication of diabetes mellitus. The proposed mechanisms for erectile dysfunction in diabetes include central and autonomic neuropathy, endothelial dysfunction, and smooth muscle dysfunction. The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in centrally mediated penile erection. This study was designed to examine the role of nitric oxide (NO) within the central nervous system component of the behavioral responses including erection in diabetic rats. N-methyl-D-aspartic acid (NMDA)-induced erection, yawning, and stretch through the PVN can be blocked by prior administration of NO synthase (NOS) blocker, L-NMMA, in freely moving, conscious male normal rats. Four weeks after streptozotocin (STZ) and vehicle injections, NMDA-induced erection, yawning, and stretch responses through the PVN are significantly blunted in diabetic rats compared with control rats. Examination of neuronal NOS (nNOS) protein by Western blot analysis indicated a reduced amount of nNOS protein in the PVN of rats with diabetes compared with control rats. Furthermore, restoring nNOS within the PVN by gene transfer using adenoviral transfection significantly restored the erectile and yawning responses to NMDA in diabetic rats. These data demonstrate that a blunted NO mechanism within the PVN may contribute to NMDA-induced erectile dysfunction observed in diabetes mellitus.

Animals↗

Intracavernosal vascular endothelial growth factor (VEGF) injection and adeno-associated virus-mediated VEGF gene therapy prevent and reverse venogenic erectile dysfunction in rats.

Penile veno-occlusive dysfunction (venogenic erectile dysfunction) is a common cause of erectile dysfunction (ED). We investigated whether vascular endothelial growth factor (VEGF) can be used to prevent and reverse venogenic ED in a rat model. Pharmacological cavernosometry was developed and validated using adult male rats with either arteriogenic or venogenic ED. Castrated animals were treated with intracavernous VEGF as either a recombinant protein (C+VEGF) or adeno-associated virus (AAV)-mediated VEGF gene therapy (C+VEGF gene) in an attempt to prevent the development of venogenic ED. Other animal groups received testosterone replacement (C+testosterone) or intracavernous AAV-LacZ gene (C+LacZ). Animals with documented venogenic ED were treated with intracavernous VEGF in an attempt to reverse their ED. Functional analysis (pharmacological infusion cavernosometry) was performed following treatment. Penile specimens were harvested for immunohistochemistry and electron microscopic evaluation. Castrated rats showed a decrease in papaverine-induced intracavernous pressure and an increase in maintenance and drop rates during pharmacological cavernosometry. These changes were prevented by systemic testosterone and intracavernous VEGF or AAV-VEGF therapy. Moreover, intracavernous VEGF was able to reverse the venogenic ED produced by castration. The quantity of penile smooth muscle detected by alpha actin staining decreased after castration but not in the C+T, C+VEGF, or C+VEGF gene groups. Transmission electron microscopy revealed atrophy of penile smooth muscle cells and nerves in the castrated rats. In VEGF-treated rats, regeneration of smooth muscle and nerves as well as endothelial cell hypertrophy and hyperplasia were the prominent features. In our animal model, systemic testosterone replacement or intracavernous VEGF (protein and VEGF gene) prevented the veno-occlusive dysfunction in castrated animals. In rats with established venous leakage, VEGF treatment reversed the cavernosometric findings of leakage. Intracavernous injection of either VEGF protein or VEGF gene may be a preferred therapy to preserve erectile function in patients in whom testosterone therapy is contraindicated.

Adenoviridae↗

Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis.

AIMS: Coronary endothelial dysfunction (CED) precedes atherosclerosis and is associated with cardiovascular events. Both CED and erectile dysfunction (ED) are partly mediated by impairment in the nitric oxide pathway. ED is associated with established coronary atherosclerosis, but its relationship with early coronary atherosclerosis and CED is unknown. This study was designed to test the hypothesis that CED is associated with ED in men with early coronary atherosclerosis. Moreover, the role of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) was investigated; ADMA is a novel endogenous competitive inhibitor of nitric oxide synthase and has been shown to be an independent marker for cardiovascular disease. METHODS AND RESULTS: Fifty-six men without obstructive coronary artery disease (CAD) who underwent coronary endothelial function testing were studied. ADMA levels were determined and all men were asked to complete the International Index of Erectile Function-5 questionnaire to assess erectile function. Patients were divided according to the presence (n = 32) or absence (n = 24) of CED. Men with CED had significant impairment of erectile function (P = 0.008) and significantly higher ADMA levels (0.50 +/- 0.06 vs. 0.45 +/- 0.07 ng/mL, P = 0.017) compared with men with normal endothelial function. Erectile function positively correlated with coronary endothelial function. This correlation was independent of age, body mass index, high-density lipoprotein, C-reactive protein, homeostasis model assessment of insulin resistance index, and smoking status. CONCLUSION: CED is independently associated with ED and plasma ADMA concentration in men with early coronary atherosclerosis. This study further supports the role of the endothelium in systemic vascular diseases and the role of ADMA in the systemic manifestations of endothelial dysfunction.

Arginine↗

Negative stress echocardiographic study predicts excellent long-term prognosis in patients with erectile dysfunction.

BACKGROUND: Subjects with erectile dysfunction share common risk factors as those for coronary artery disease. However, there are no data on the role of stress echocardiography in assessing the prognosis of patients with erectile dysfunction. HYPOTHESIS: We sought to determine the prognostic utility of negative stress echocardiography study in subjects with erectile dysfunction and compare it to similar subjects without erectile dysfunction. METHODS: Between October 1996 and December 1997, 236 patients had negative stress echocardiograms. There were 28 patients with erectile dysfunction. There was a higher prevalence of diabetes in the erectile dysfunction group (64% vs. 35%, P=0.005). The prevalence of other risk factors was similar in the two groups. Follow-up was obtained for 233 patients for a mean duration of 25 months. RESULTS: At the end of follow-up, there was no significant difference in the annualized occurrence of cardiac events between the two groups (4.6% vs. 4.3%, P=NS). Of note, none of the patients were prescribed sildenafil and none of the cardiac events were related to sexual activity. CONCLUSIONS: Our study shows that subjects with erectile dysfunction who have a negative stress echocardiographic study have a comparable event rate to similar subjects at high risk for cardiac events on long-term follow-up.

Chi-Square Distribution↗

Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction.

The prevalence of erectile dysfunction rises rapidly with age and is a frequent complaint presented in clinical practice. Although the etiology of erectile dysfunction is multifactorial, 10-20% of evaluations demonstrate testosterone deficiency. Testosterone deficiency due to secondary hypogonadism increases with age. Despite a higher prevalence of secondary hypogonadism in the elderly, there are no studies addressing hypothalamic-pituitary structural abnormalities in elderly impotent men with testosterone deficiency. We retrospectively reviewed the records of all elderly men who presented for general outpatient evaluation of erectile dysfunction from 1996 to 1999. To obtain a cohort control population, the records of 300 patients without erectile dysfunction were also reviewed. Amongst the erectile dysfunction patients, 225 were found to be testosterone deficient (testosterone < 300 ng/dl). Of these patients, 29 were additionally diagnosed with secondary hypogonadism based on a luteinizing hormone (LH) < 13 mIU/ml. Magnetic resonance imaging (MRI) or computed tomography (CT) imaging was available and reviewed in all patients diagnosed with secondary hypogonadism. Ten per cent of these patients had hypothalamic-pituitary imaging abnormalities. The prevalence of pituitary tumors within our population was not significantly elevated compared to the previous general population studies. Small-vessel white matter disease, hyperlipidemia and history of compression fractures were significantly increased in both univariate and multivariate analysis in the erectile dysfunction group compared with the control cohort. This study does not suggest that the use of hypothalamic-pituitary imaging in the evaluation of impotence in elderly men, in the absence of clinical characteristics of other hormonal loss or sella compression symptoms, will increase diagnosis of structural hypothalamic-pituitary abnormalities over that of the general population. However, the yield may increase with very low testosterone levels. These data suggest that there is an increase in ischemic white matter disease in elderly men with hypogonadism that may reflect microvascular injury to the hypothalamic-pituitary. Furthermore, these data confirm that low testosterone is associated with hyperlipidemia in the elderly. Future studies are required to assess the role of hypogonadism and hyperlipidemia, and to determine if treatment of the hormone deficiency improves the lipid profile.

Aged↗