Nonorganic Erectile Dysfunction Research Articles

Nutraceutical interventions for erectile dysfunction: a systematic review and network meta-analysis.

Although nutraceutical-based treatments are often offered for erectile dysfunction (ED), their efficacy remains doubtful, and the choice of one substance over the other is challenged by the dearth of head-to-head comparative studies. We aimed to compare the efficacy of available nutraceutical interventions, alone or in combination with phosphodiesterase type 5 inhibitors (PDE5i), in improving erectile function in men with ED through a network meta-analysis (NMA), which incorporates direct and indirect evidence into one model thus generating a hierarchy of effectiveness. PubMed, Scopus, Web of Sciences, and Cochrane Library databases were searched for randomized placebo-controlled trials (RCTs) assessing the effect of any nutraceutical regimen in improving erectile function when compared to each other, placebo, and/or PDE5i in men with ED. Data were included in a random-effects NMA, where efficacy of treatments was ranked by surface under the cumulative ranking curve (SUCRA). Two NMAs were also conducted separately for organic and non-organic ED. Reciprocal comparisons between all treatments were analyzed by league tables. The main outcome was the standardized mean difference in the score of the International Index of Erectile Function (IIEF)-5 or IIEF-6. Fifteen RCTs provided information on 1000 men with ED. In the overall NMA, compared to placebo, the combination propionyl L-carnitine (PLC) + acetyl L-carnitine (ALC) + Sildenafil was associated with the highest SUCRA (97%) in improving erectile function score, followed by L-Arginine + Tadalafil (84%), Sildenafil (79%), Tadalafil (72%), and L-Arginine (52%). No other treatment regimen showed efficacy with statistical significance. In patients with organic ED, the efficacy of Sildenafil and Tadalafil was significantly improved by PLC + ALC and L-Arginine, respectively. On the contrary, in non-organic ED, nutraceuticals did not improve the therapeutic performance of daily Tadalafil. This NMA contributes valuable insights into the potential of nutraceutical interventions for ED. We employed strict inclusion criteria related to study design and diagnostic tool, ensuring the assumption of transitivity and the consistency of the analysis. Against a background of general ineffectiveness of most nutraceutical interventions, L-Arginine and the mix PLC + ALC appeared to be of some usefulness in improving erectile function, especially in combination with PDE5i in organic ED.

Erection Hardness Score in Masturbation Can Serve as a Preliminary Screening Tool for Organic Erectile Dysfunction

To explore the efficacy, in terms of sensitivity and specificity, of Erection Hardness Score (EHS) applied to masturbation in diagnosing predominantly organic erectile dysfunction (ED), compared to the actual standard, which is nocturnal penile tumescence and rigidity (NPTR). A total of 189 consecutive patients who came to our outpatient clinic from October 2019 to October 2020, reporting ED and an abridged International Index of Erectile Function (IIEF-6) score <26 were enrolled. Patients filled out two psychometric questionnaires: the IIEF-6 applied to partnered intercourse and the EHS applied to masturbation, then they underwent the NPTR test with Rigiscan for 2 consecutive nights in good sleep condition. Sensitivity, specificity, positive predictive value, and negative predictive value of EHS and IIEF-6 scales with NPTR as the standard, as well as the correlation between EHS, IIEF-6, and NPTR results were calculated. Results show that the sensitivity of the EHS scale for the diagnosis of ED was 60.0%, the specificity was 95.7%, the positive predictive value was 83.3%, the negative predictive value was 86.9%, and the coincidence rate was 86.2%. The correlation coefficient was 0.572 and the area under the ROC curve was 0.78, which means the strength of erection in masturbation as evaluated by the EHS can effectively help in discriminating between predominantly organic and apparently nonorganic ED. An EHS score of 3-4, meaning good-optimal erectile function during masturbation, decreases the likelihood of predominantly organic ED and reduces the need for further NPTR testing.

Dopamine D2 receptors in the nucleus accumbens modulate erectile function in a rat model of nonorganic erectile dysfunction.

BackgroundThe central molecular mechanisms of nonorganic erectile dysfunction remains unknown.ObjectiveThis study aimed to investigate the association of dopaminergic neurons projecting to the nucleus accumbens of male rats with nonorganic erectile dysfunction.Materials/methodsNonorganic erectile dysfunction was induced by chronic mild stress. The sucrose consumption test, sexual behavior test, and apomorphine test were carried out to select depression‐like rats with erectile dysfunction. These rats were considered as nonorganic erectile dysfunction model rats. Dopamine D1/D2 receptor agonist/antagonist was infused into the nucleus accumbens to observe the effect on sexual behavior. Dopaminergic projections to the nucleus accumbens were labeled with both the retrograde tracer FluoroGold injected into the nucleus accumbens and tyrosine hydroxylase. The expression level of tyrosine hydroxylase in dopaminergic neurons projecting to the nucleus accumbens in the ventral tegmental area was measured. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the nucleus accumbens were also measured.ResultsNonorganic erectile dysfunction was proved by the sucrose consumption test, sexual behavior test, and apomorphine test in model rats. After central infusion of the dopamine D2 receptor agonist into the nucleus accumbens, the recovery of erectile function, sexual arousal, and motivation were indicated by increased intromission ratio and decreased mount latency. Decreased expression levels of dopamine D2 receptors and tyrosine hydroxylase in the nucleus accumbens and decreased expression level of tyrosine hydroxylase in the dopaminergic neurons projecting to the nucleus accumbens were observed in model rats.DiscussionThese results suggest the impairment of dopaminergic neurons projecting to the nucleus accumbens and dopamine D2 signaling in the nucleus accumbens, causing the suppression of erectile function, sexual arousal, and motivation.ConclusionThese results suggest that the impaired dopamine D2 receptor pathway in the nucleus accumbens may be one of the main pathway involved in the development of nonorganic erectile dysfunction in the present model.

Development of an indigenous manual of cognitive behavior sex therapy for young men.

Some studies with Western men have shown promising results for the efficacy of cognitive behavior sex therapy (CBST) in the treatment of erectile dysfunction. The two randomized controlled trials were conducted to assess the efficacy of CBST as a treatment of choice for young men with non-organic erectile dysfunction (NOED). The two randomized controlled trials were run to assess the efficacy of CBST and integrated treatment approaches for the treatment of NOED in young Pakistani men. The two studies were registered with ClinicalTrials.gov vide No. NCT04179747 and NCT04126252. The sex therapy techniques were combined with cognitive behavior therapy and mindfulness to develop an indigenous approach for the treatment of NOED in young Pakistani men. The CBST significantly improved International Index of Erectile Functioning-5 scores in two studies. The CBST also decreased depression scores associated with NOED. The CBST is a treatment of choice for young Pakistani men with NOED. The CBST is also significant in improving the mental health conditions associated with NOED.

Randomized Placebo Controlled Trial of Sildenafil Citrate, Cognitive Behavior Sex Therapy and Integrated Treatment in Men Diagnosed With Non Organic Erectile Dysfunction.

IntroductionThe integrated treatment combining phosphodiesterase-type 5 inhibitors (PDE5i) and Cognitive Behavior Sex Therapy (CBST) has been shown to yield promising results in the treatment of Non Organic Erectile Dysfunction (NOED) in young men.AimThe current study aimed to establish the efficacy of integrated treatment combining Sildenafil Citrate (SC) 50mg and CBST as a treatment of choice in young Pakistani men with NOED.MethodsOne hundred thirty-seven young men were recruited to participate in the study out of 164 men referred from sexual health clinics in Pakistan. They were randomized sequentially into 4 treatment groups namely SC = 35, CBST = 34, integrated treatment = 35, and placebo = 33. 7, 4, 6, and 4 men were dropped out of each treatment group respectively. The data of 116 men were analyzed. The on demand SC 50 mg, twice weekly 50 minutes sessions and home assignments, a combination of SC and 50 minutes sessions, and placebo were administered to firsst, second, third, and fourth group respectively for a period of 12 weeks. The follow-up assessment was done after 12 weeks of post-treatment for all groups.Main Outcome MeasuresThe Urdu standardized versions of International Index of Erectile Functoning-5 (IIEF-5) and Depression Anxiety Stress Scale-21 (DASS-21) were the main outcome measures.ResultsThe mixed repeated measures analysis of co-variance yielded significant impact of both CBST and integrated treatment groups in improving IIEF-5 scores at post treatment as compared to placebo. The CBST group experienced reduction in depression scores at post treatment as compared to both SC and integrated treatment. Only the integrated treatment brought reduction in anxiety scores at post treatment as compared to SC. The covariates age and NOED duration did not significantly impact the treatment outcome for all treatment groups.Clinical ImplicationsThe efficacy of integrated treatment approach for improving symptoms of NOED and associated depression and anxiety is strong clinical implication of the study.Strengths & LimitationsThe effectiveness of integrated treatment approach in the improvement of NOED symptoms and associated depression and anxiety scores is the main strength of the study. The improvement in depression scores is the added strength of CBST component of integrated treatment approach. The study should have included other PDE5i to compare their effects with the CBST or placebo groups.ConclusionThe study concludes that the CBST and integrated treatments are treatment of choice for NOED and associated depression and anxiety in young men.Bilal A, Abbasi NH. Randomized Placebo Controlled Trial of Sildenafil Citrate, Cognitive Behavior Sex Therapy and Integrated Treatment in Men Diagnosed With Non Organic Erectile Dysfunction. Sex Med 2022;10:100464.

Differences in Penile Hemodynamic Profiles in Patients with Erectile Dysfunction and Anxiety.

Background: Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. Aim: To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED. Methods: Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 μg. Results: In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = −0.9, p < 0.01), 10 (r = −0.9, p < 0.01), 15 (r = −0.9, p < 0.01), and 20 (r = −0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a “late-responder” profile. Conclusion: If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED, since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.

International Index of Erectile Functioning-5: A Critical Appraisal

Background: Some studies have reported methodological flaws and shortcomings in the International Index of Erectile Functioning-5 (IIEF-5) which is a self-report measure for the assessment of erectile dysfunction (ED). Aim: The aim of this research is to point out methodological flaws and shortcomings in IIEF-5 when used with Pakistani men. Settings and Design: Two independent clinical trials were run to assess the efficacy of different forms of treatment for ED in young Pakistani men. Materials and Methods: The IIEF-5 in Urdu version was employed to diagnose and assess the severity of ED in young men at 3 time points. Results and Conclusions: Several flaws and shortcomings were noted including the unidimensionality of the scale, categorization of the scale into severity categories based on cutoff points, the inability of the scale to differentiate between organic and nonorganic ED, double barrel item statement, and lack of standardized translation in local or regional languages of Pakistan. The validity of IIEF-5 can be increased if the above-mentioned flaws and shortcomings are addressed.

Cognitive Behavioral Sex Therapy: An Emerging Treatment Option for Nonorganic Erectile Dysfunction in Young Men: A Feasibility Pilot Study.

IntroductionAn increasing number of young men have been found to develop nonorganic erectile dysfunction (NOED) in recent years. The NOED has been shown to respond better to cognitive behavior sex therapy (CBST) in a few past studies.AimThe present research aims to establish the efficacy of CBST as a promising treatment option in young men suffering from NOED by administering a feasibility pilot trial.Methods28 young men (M = 31 years) out of a total of 39 men (7 excluded, 4 quit treatment) diagnosed with NOED from sexual health clinics in Pakistan were recruited to receive CBST treatment (n = 13) on average twice a week for a period of 50 minutes per session for a period of 4, 6, 8, and 12 weeks for the mild, mild to moderate, moderate, and severe forms of NOED, respectively, and sildenafil citrate group (n = 15) receiving sildenafil citrate 50 mg on demand. The trial design was sequential random assignment clinical trial.Main Outcome MeasuresInternational Index of Erectile Functoning-5 and Depression Anxiety Stress Scale-21 were used before treatment, after treatment, and in follow-up as the main outcome measures.ResultsThe repeated measures analysis of covariance established a nonsignificant difference between CBST and sildenafil citrate 50 mg in NOED scores improvement, NOED severity reduction, and reduction in depression scores at posttreatment assessment. There were significant differences among different CBST modalities in improving NOED scores, reduction in NOED severity, and depression scores. There was significant difference in CBST and sildenafil citrate 50 mg in anxiety reduction at posttreatment assessment. The covariates age, age groups, and NOED duration did not significantly impact the treatment outcome for both treatment groups except age which impacted the interaction of treatment and anxiety scores.ConclusionThe CBST is an emerging and promising treatment choice in younger men suffering from NOED.Bilal A, Abbasi NuH. Cognitive Behavioral Sex Therapy: An Emerging Treatment Option for Nonorganic Erectile Dysfunction in Young Men: A Feasibility Pilot Study. J Sex Med 2020;8:396–407.

Re: An Evaluation of a Clinical Care Pathway for the Management of Men with Nonorganic Erectile Dysfunction.

Re: An Evaluation of a Clinical Care Pathway for the Management of Men with Nonorganic Erectile Dysfunction.

An Evaluation of a Clinical Care Pathway for the Management of Men With Nonorganic Erectile Dysfunction

IntroductionThere exists little literature on the outcomes of the medical management of men with erectile dysfunction (ED) with no overt organic etiology. AimThis study was conducted to assess the outcomes of men with nonorganic ED treated medically. MethodsAll patients had normal hormone profiles and vascular assessment. All were given a trial of a phosphodiesterase type 5 inhibitor (PDE5i). If no improvement was experienced, intracavernosal injection (ICI) therapy was administered. All patients were encouraged to seek a consultation with a mental health professional. Main Outcome MeasurePatient demographics, medical comorbidities, hormone and hemodynamics assessments, and change in International Index of Erectile Function scores of patients were recorded. Results116 men with a mean age or 38 ± 19 (range 16−57) years were studied. 21% had mild ED, 47% had moderate ED, and 32% had severe ED. 21% had seen a psychiatrist. 81% of patients responded to PDE5i with a penetration hardness erection on follow-up (mean duration of 7 ± 3 months postcommencement of PDE5i). However, only 68% of these were capable of a consistently good response. The mean Erectile Function domain score on PDE5i for the entire group improved from 18 ± 11 to 22 ± 6 (P = .01), and for PDE5i responders it was 27 ± 4 (P < .001). 28% of men (22 PDE5i failures and 10 with a mixed response to PDE5i) attempted ICI, all obtaining consistently functional erections. At a mean time point of 11 ± 5 months, 83% of those responding to PDE5i had ceased using PDE5i due to a lack of need. 11% of those using ICI continued to use them 6 months after starting ICI; the remainder had been transitioned back to PDE5i. Of the 29 patients in the latter subgroup, 66% were no longer using PDE5i consistently due to a lack of need. Clinical ImplicationsNot all men with nonorganic ED respond to PDE5i initially and many of those who respond do so only intermittently; such patients are potentially curable, using erectogenic pharmacotherapy for erectile confidence restoration, most men are capable of being weaned from drug therapy. Strengths & LimitationsThe strengths of the study are the large number of patients and the use of serial validated instruments to assess erectile function outcomes. As a weakness, despite normal hormone and vascular assessments, the diagnosis of nonorganic ED is still a presumptive one. ConclusionMedical management of nonorganic ED utilizing the process of care model results in cure in a large proportion of such patients. The transient use of ICI in some patients permits successful PDE5i rechallenge.Jenkins LC, Hall M, Deveci S, et al. An Evaluation of a Clinical Care Pathway for the Management of Men With Nonorganic Erectile Dysfunction. J Sex Med 2019;16:1541–1546.

Dopamine D2 receptors in the basolateral amygdala modulate erectile function in a rat model of nonorganic erectile dysfunction.

Nonorganic erectile dysfunction is a problem with unknown central mechanisms. Changes in brain activity in the amygdala have been observed in human patients. This study aimed to investigate the dopamine system in the basolateral amygdala of male rats with nonorganic erectile dysfunction. We applied chronic mild stress to induce nonorganic erectile dysfunction. After exposure to chronic mild stress, the sucrose consumption test, sexual behaviour test and apomorphine test were used to select depression-like rats with erectile dysfunction as nonorganic erectile dysfunction model rats. The sexual behaviour of these rats after central infusion of a dopamine D1/D2 receptor agonist/antagonist was observed. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the basolateral amygdala were also measured. The result of the sucrose consumption test, sexual behaviour test and apomorphine test indicated a successful nonorganic erectile dysfunction model. Central infusion of a dopamine D2 receptor agonist increased intromission ratio in model rats. Lower expression levels of tyrosine hydroxylase and the dopamine D2 receptor in the basolateral amygdala were observed in rats with nonorganic erectile dysfunction. These results suggest that impairment of the dopamine D2 receptor pathway in the basolateral amygdala may contribute to the development of nonorganic erectile dysfunction.

SOP Conservative (Medical and Mechanical) Treatment of Erectile Dysfunction

Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships. The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures. The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included. Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation.

Subclinical endothelial dysfunction and low-grade inflammation play roles in the development of erectile dysfunction in young man with low risk of coronary heart disease

Introduction and ObjectivesThere is a close relationship between erectile dysfunction (ED) and cardiovascular disease. However, many young patients presenting with ED do not have clinical cardiovascular disease and even other...

Impact of Nonorganic Erectile Dysfunction on Spouses: A Study from India

The overall outcome of men with erectile dysfunction (ED) depends a lot on participation in treatment of their partners/spouses. However, psychosexual functioning of partners/spouses has received scant attention. To study the psychosexual functioning of spouses of men with nonorganic ED in terms of their sexual satisfaction, psychological problems, marital adjustment, quality of life, and level of dysfunction. The main outcome measures for the partners of men with ED were symptom questionnaire, marital questionnaire (KDS-15 marital questionnaire), sexuality scale, quality of life enjoyment and satisfaction questionnaire, dyadic adjustment scale, and dysfunction analysis questionnaire. Spouses of men with ED (n=50) and spouses of men without any psychosexual dysfunction (n=50) were compared for sexual and marital function, quality of life, and dyadic adjustment. The psychological impact was assessed by symptom questionnaire. Spouses of men with ED have significantly lower levels of marital and sexual satisfaction and higher levels of psychiatric symptoms than controls. Furthermore, the spouses of men with nonorganic ED also report poor quality of life in most domains of life and had higher level of dysfunction. Our findings support the Western data with regard to the psychosexual functioning of spouses/partners of men with ED and suggest that spouses/partners of men with ED should also be assessed thoroughly.

Intracavernous Injection of Papaverine for Erectile Failure R. Virag

I n 1982 in a letter to the editor of The Lancet [1], Virag exposed to the English literature the ability of an intracavernous injection of papaverine to induce an erection. He stated that an accidental intracavernous injection of that drug during an arterial epigastric cavernous anastomosis [2], a vascular procedure proposed to treat vasculogenic erectile dysfunction (ED), had produced a rigid erection for 2 hours. After this finding, Virag decided to study the effect of papaverine in the physiology of erection. He studied 15 patients with organic ED and 10 with non-organic ED. Eighty milligrams of papaverine were injected into one corpora cavernosa and continuous recording of intracavernous pressure (ICP) was done through a 21 G needle inserted in the contralateral corpora cavernosa. Duplex ultrasound and pulse plethysmography were used for continuous monitoring of penile arterial vessels. In same cases, selective bilateral internal iliac angiography was performed. After papaverine injection, there was an ICP increase; this increase was higher when patient were under general anesthesia (mean of 70 mm Hg against 40 mm Hg without anesthesia). An increase on arterial flow was seen by duplex ultrasound, pulse plethysmography, and angiography; the peak effect was seen after 2–15 minutes after injection and lasted from 10 to 120 minutes. According to Virag, 7 out of 15 patients with organic ED reported improvement on their erections in the days following the study. All of seven had arterial ED. There was no improvement on patients with non-organic ED. Based on those results, Virag started a “conservative therapy” in 30 patients with ED who had Doppler and arteriographic evidence of penile arterial insufficiency, including 12 with diabetes mellitus. Patients received an intracavernous injection of 80 mg of papaverine and after 15 minutes, an infusion of saline with 1% of heparin via an infusion pump until they reached a rigid erection which was maintained for 15 minutes. The procedure was performed without anesthesia and was repeated after 2 months and every third month after that. Of the 14 patients who had at least two procedures, called by Virag as artificial erections, four returned to their “normal sexual life,” nine reported significant improvement in their penile rigidity, and one had no change in his erectile function. Virag concluded that papaverine was a powerful smooth-muscle relaxant, possibly acting as phosphodiesterase inhibitor or with an antinicotinic effect; to him, artificial erections were associated to vasodilation of pudendal arteries branches and with a possible “mechanical action” at the level of cavernous tissue. Sidney Glina

Combined cardiac sympathetic excitation and vagal impairment in patients with non-organic erectile dysfunction

Patients with non-organic erectile dysfunction (ED) frequently present with syndromes involving systemic sympathovagal dysfunction. The linkage of ED to cardiac autonomic regulation is not well understood. Forty-four men with non-organic ED and 38 healthy age-matched control subjects with ages ranging from 40 years to 69 years were recruited. These two groups were divided into three distinct age categories at 10-year intervals. Patients were divided into three different severity categories, among whom 35 patients received a two-month oral treatment of trazodone. Power spectral analysis of successive R-R intervals (RR) was performed to evaluate the variance (variance of RR-interval values), the high-frequency power (HF), and the ratio of low-frequency power to HF (LF/HF) of their heart rate variability (HRV). Patients exhibited a significantly lower variance and HF, but a higher LF/HF compared to the control group across all age categories. The changes in variance and HF were severity dependent. In addition, all the HRV parameters of the patients with a satisfactory response after treatment have significantly improved. The results indicate that patients with non-organic ED had significant cardiac sympathetic hyperactivity and severity-dependent cardiac vagal impairment. Non-organic ED may be accompanied by an abnormality in cardiac autonomic regulation.

Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users

Aim of the study was to evaluate whether endothelial dysfunction is a marker of erectile dysfunction (ED) in recreational drug abuse. Sixty-four non-consecutive men complaining of ED from at least 3 months were included. All patients underwent detailed history about recreational drug abuse and were then submitted to dynamic penile duplex ultrasound (PDU). According to pharmaco-stimulated peak systolic velocity (PSV) cutoff at 35 cm s(-1), patients were divided into two groups: organic (O; n=30) and non-organic (NO; n=34) ED. All subjects and 7 healthy age-matched subjects as controls, underwent veno-occlusive plethysmography (VOP) for the evaluation of endothelium-dependent dilatation of brachial arteries. Blood pressure, total and free testosterone, prolactin, estradiol, low-density lipoprotein and high-density lipoprotein cholesterol were also evaluated; patients were classified with regard to insulin resistance through the HOMA-IR index. Cannabis smoking was more frequent in O-ED vs NO-ED (78% vs 3%, P<0.001) in the absence of any concomitant risk factor or comorbidity for ED. VOP studies revealed impaired endothelium-dependent vasodilatation in O-ED but not in NO-ED and controls (12+/-6 vs 32+/-4 and 34+/-5 ml min(-1), respectively; P=0.003). Overall patients showed a direct relationship between HOMA-IR and PSV (r(2)=0.47, P<0.0001), which was maintained in men with organic ED (r(2)=0.62, P<0.0001). In cannabis consumers, a direct relationship between HOMA-IR and VOP was also found (r(2)=0.74, P<0.0001). Receiver-operating characteristic (ROC) curve analysis revealed that VOP values below 17.22 ml min(-1) were suggestive for vasculogenic ED. We conclude that early endothelial damage may be induced by chronic cannabis use (and endocannabinoid system activation); insulin resistance may be the hallmark of early endothelial dysfunction and may concur to determine vascular ED in the absence of obesity. Further studies are warranted to establish a direct relationship between cannabis abuse, onset of insulin resistance and development of vascular ED.

Incidence of extragenital vascular disease in patients with erectile dysfunction of arterial origin

This research was carried out to evaluate the prevalence of carotid and/or lower limb artery abnormalities in patients with arterial erectile dysfunction (ED). To this end, patients with ED (Andrology Unit) or suspected peripheral atherosclerosis (Angiology Unit) underwent an independent and parallel echo-Duplex examination. The Andrology Unit examined 167 patients with ED of different etiologies: 52 of them had penile artery insufficiency and consequently their carotids and lower limb arteries had to be evaluated by means of echo-Doppler. In all, 36 out of the 46 patients with nonarterial organic ED and 22 out of the 69 patients with nonorganic ED underwent the same evaluation and served as controls. The Angiology Unit enrolled 457 ED patients who initially underwent echo-Doppler for suspected carotid and/or arterial leg atherosclerosis and subsequently dynamic echo-Doppler. Isolated penile artery insufficiency was found in 23.1 and 25% of the patients evaluated in the Angiology and Andrology Units, respectively. The remaining patients were shown to have ED associated with an atheroma or marked intima-media thickness of the carotid vessels and/or of leg arteries. The frequency of penile arterial insufficiency and of carotid and/or lower limb artery abnormalities was significantly higher (P < 0.01) compared to that found in patients with ED of nonarterial organic or psychogenic origin. Both Units found that the frequency of penile artery insufficiency and carotid or lower limb artery abnormalities was significantly higher than that of penile artery insufficiency alone or plus both carotid and lower limb artery abnormalities. This study showed that penile artery insufficiency is associated with carotid and/or lower limb artery ultrasound abnormalities in about 75% of the cases. Therefore, arterial ED may be regarded as a sign of a more generalized atherosclerosis.

Combined oral therapy with sildenafil and doxazosin for the treament of non-organic erectile dysfunction refractory to sildenafil monotherapy

The purpose of this work was to investigate the efficacy and safety of sildenafil in combination with doxazosin for the treatment of non-organic erectile dysfunction in patients who did not respond to sildenafil. We enrolled 28 patients with non-organic erectile dysfunction, for whom 3 months of sildenafil monotherapy had failed. They were divided in two random and homogeneous groups: 14 were treated with doxazosin (4 mg daily) and sildenafil (100 mg 1 h before sexual intercourse); the other 14 patients received sildenafil and placebo. The results were assessed by means of the IIEF questionnaire before the beginning of the study, after 30 days of therapy and after 60 days. Of the 14 patients treated with doxazosin and sildenafil, 11 (78.6%) showed a statistically significant increase of IIEF; in the placebo group, only one patient (7.1%) recorded a significant IIEF increase. The differences observed in the two groups were statistically very significant (P=0.0016). Blood pressure did not show significant alterations. Side effects were minimal and even present during sildenafil monotherapy. The combination therapy with sildenafil and doxazosin resulted in the safe and effective treatment of men with non-organic erectile dysfunction for whom sildenafil alone had failed.

Apomorphine test: a beneficial clue for planning bromocriptine treatment in non-organic erectile dysfunction

Apomorphine test: a beneficial clue for planning bromocriptine treatment in non-organic erectile dysfunction