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Plasma transforming growth factor-beta1 levels in patients with erectile dysfunction.

AIM: To evaluate the plasma TGF-beta1 level in erectile dysfunction (ED) patients of various causes. METHODS: Sixty-two patients with ED and 26 potent men were subjected to the study. Based on multidisciplinary work-ups, including medical history, physical examinations, blood tests with lipid profile and hormones, penile duplex Doppler ultrasonogram and neurophysiological tests, causes for ED were classified as psychogenic (n=15), neurogenic (n=16) and vasculogenic (n=31). The plasma TGF-beta1 level was measured by the ELISA method. RESULTS: The plasma TGF-beta1 level was significantly increased in the ED group (6.7+/-4.9 ng/mL), compared to the control (4.0 +/-2.1 ng/mL) (P<0.01). In the ED groups, there was a significant increase in the vasculogenic group (9.0 +/-5.5 ng/mL), compared to the psychogenic (3.8 +/-1.8 ng/mL) and neurogenic groups (4.8+/-3.2 ng/mL) (P<0.01). Of the vascular risk factors, both the smoking (7.5 +/-4.7 ng/mL) and dyslipidemia groups (7.4+/-4.4 ng/mL) showed significantly increased plasma TGF-beta1 levels, compared to the non-smokers (5.5+/-2.8 ng/mL), and those without dyslipidemia (4.8+/-2.8 ng/mL) (P<0.05). CONCLUSION: Vascular risk factors are associated with an elevated plasma TGF-beta1 level, which may contribute to cavernous fibrosis and ED.

Adult↗

Penile duplex pharmaco-ultrasonography of cavernous arteries in men with erectile dysfunction and generalized atherosclerosis.

Assessment of cavernosal perfusion in men with erectile dysfunction (ED) relies on Doppler spectrum analysis of pharmachologically stimulated peak systolic velocity (sPSV) in cavernous arteries but its accuracy in identifying men affected by a cavernosal perfusion disorder correlated with atherosclerosis remains undefined. We estimated by B-mode ultrasound, the accuracy of sPSV of cavernous arteries to identify ED with an expected cavernosal perfusion disorder. This was predicted by an elevated intima-media thickness (IMT) of common carotid arteries, a reference methodology to estimate the degree of generalized atherosclerosis, in men exposed to vascular risk factors (VRFs). sPSV and IMT were evaluated in 269 men with ED, 49 had no VRFs, 100 were overweight with/or without hyperlipidaemia, 120 were affected by type 2 diabetes and/or essential hypertension. sPSV was significantly lower (p<0.05) in patients with VRFs associated with atherosclerosis (IMT>or=1 mm) (n=39) than in men with no VRFs and no atherosclerosis (n=49). sPSV correlated negatively with age (p<0.0001), with serum% of glycated haemoglobin (p=0.010) and with carotid artery IMT (p=0.013). An sPSV or=1 mm combined to the exposure to VRFs. The ultrasonographic evaluation of sPSV had a very limited accuracy in discriminating ED with an expected cavernosal perfusion disorder, based on the presence of a generalized atherosclerosis in men with VRFs.

Adult↗

Successful withdrawal of oral long-acting nitrates to facilitate phosphodiesterase type 5 inhibitor use in stable coronary disease patients with erectile dysfunction.

INTRODUCTION: Vascular disease is the most common cause of male erectile dysfunction (ED). Phosphodiesterase type 5 (PDE5) inhibitors are effective in up to 80% of men but are contraindicated in the presence of oral nitrates, because of a potentially severe hypotensive interaction. AIMS: To see if stable coronary disease patients with ED could have their oral nitrates discontinued to allow safe use of a PDE5 inhibitor. METHODS: Prospective study of 425 men with ED and cardiac disease conducted in an outpatient cardiac sexual advice clinic. MAIN OUTCOME MEASURES: Discontinuation of oral nitrates to facilitate subsequent use of PDE5 therapy. RESULTS: Oral nitrates were being used by 88 (21%) coronary artery disease patients all of whom were clinically stable. Fifty-five (63%) of these men with a good exercise ability had their nitrates discontinued in the presence of continuing beta-blockade or calcium antagonist therapy. They were reviewed 1 week later. Only three restarted their nitrate therapy because of an increase in symptoms. Forty-nine of the 52 men no longer taking nitrates were treated with a PDE5 inhibitor which was effective in 22 out of 26 (85%) patients who have completed follow-up. Fifteen patients are currently undergoing clinic follow-up in order to optimize treatment, and nine patients have continued therapy with their family doctors. Importantly, there have been no adverse cardiac events. CONCLUSION: Oral nitrates can be discontinued in the presence of continuing beta-blockade and/or calcium antagonist therapy in stable coronary disease patients with ED to allow for the safe use of PDE5 inhibitors.

Administration, Oral↗

Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels.

OBJECTIVE: Lack of sexual activity due to erectile dysfunction (ED) decreases testosterone (T) levels through a central effect on the hypothalamic-pituitary axis. In this paper we studied the effect of different type V phosphodiesterase (PDE5) inhibitor treatments for ED on the reversibility of this endocrine pattern. DESIGN: Open-label, retrospective study. PATIENTS: Seventy-four consecutive patients were treated on demand with sildenafil (Sild) (50 mg) and tadalafil (Tad) 20 mg. MEASUREMENTS: The success in sexual intercourse was recorded and total (tT) and free testosterone (fT) levels were studied before and after 3 months of treatment. RESULTS: Basal level of tT and fT were at the bottom of the normal range and LH levels were at the top of the high normal range. After treatments, this endocrine pattern was reversed in both groups. However, the T increase in Sild-treated patients was significantly lower than in those treated with Tad (4.7 +/- 2.7 vs. 5.1 +/- 0.9, P < 0.001). fT levels followed a directly proportional pattern, while the inverse was found when LH production was studied. The intercourse rate reflected this effect: in fact, the Sild group showed a 4.9 +/- 2.9/month full sexual intercourse rate while in the Tad group a significantly higher rate of sexual intercourse was found (6.9 +/- 4.6/month, P = 0.04). However, drug consumption was comparable between the groups (Sild 4.9 +/- 2.9 vs. Tad 4.4 +/- 2.8 pills/month, P = 0.72). CONCLUSIONS: As it is unlikely that the two drugs have a different direct effect on the pituitary-testis axis, this effect is probably due to the higher frequency of full sexual intercourse in the Tad-treated group, because of the drug's longer half-life.

3',5'-Cyclic-GMP Phosphodiesterases↗

Evaluating preference trials of oral phosphodiesterase 5 inhibitors for erectile dysfunction.

More treatment options are available now for the treatment of erectile dysfunction (ED) than ever. Treatments include oral phosphodiesterase 5 (PDE5) inhibitors, intracavernosal injections, vacuum constriction devices, and penile implants. Clinicians, researchers, and patients are interested in making direct comparisons between the response of newer treatments and that of established and more developed therapies. Of the currently available treatment options for ED, the most commonly prescribed therapies are oral PDE5 inhibitors, which include sildenafil citrate (Viagra, Pfizer Inc), tadalafil (Cialis, Lilly ICOS), and vardenafil (Levitra, Bayer). However, most patient preference studies of these drugs conducted to date have serious design flaws that hinder interpretation of the data, and thus limit the utility of the results. To make an informed decision on the most appropriate treatment option available, physicians and their patients require a thorough understanding of the methodology of these studies. Clinical comparison or preference trials must establish internal and external validity if the data are to be used in a generalized patient population. We review preference studies that compared sildenafil, tadalafil, and vardenafil, and highlight study designs that can introduce bias. We propose that, like safety and efficacy trials, randomized controlled trials (RCTs) should be the gold standard for evaluating patient preference treatments for ED. We do not wish to discourage individual investigators from performing preference studies, but rather to highlight the features of current preference trials to help patients and clinicians alike become aware of potential biases from independent or industry-sponsored patient preference trials so that they can interpret the results accordingly. Key components of patient preference RCTs are reviewed: period and carryover effects, preference assessments, eligibility criteria, and data analysis. We discuss why these components of patient-preference RCTs are important for evaluating the validity and relevance of patient preference studies. The preference studies discussed in this brief review are summarized in , and the methodological problems with each study are indicated. We provide a recommendation for the design of such trials that can minimize bias and provide better data for physicians and their patients.

3',5'-Cyclic-GMP Phosphodiesterases↗

Treatment of idiopathic erectile dysfunction in men with the opiate antagonist naltrexone--a double-blind study.

Opiate antagonists can indirectly stimulate the secretion of luteinizing hormone (LH) and testosterone, as well as sexual functions in animals and humans. We therefore treated 20 otherwise healthy men with idiopathic erectile dysfunction aged 46.3 +/- 2.7 years (mean +/- SE, range 23.9-63.3) in a double-blind study with an opiate antagonist, naltrexone, or placebo. The erectile dysfunction of these men had persisted for 3.6 +/- 0.5 years despite libido maintenance; standard procedures had excluded any organic causes. Trial duration was 12 weeks overall. After a 4-week forerun, the patients received at first 25 mg naltrexone/day orally or placebo for 4 weeks followed by 4 weeks of a 50-mg dose of naltrexone/day or placebo. Each day the patients filled out a questionnaire detailing libido, degree of erection, frequency of sexual intercourse, and spontaneous morning erections. Serum concentrations of gonadotropins and testosterone were determined radioimmunologically in the initial stage and at the end of each phase. Both patient collectives had similar initial factors. The group treated with naltrexone showed a significant rise in spontaneous early morning erections during the treatment: from 2.8 +/- 0.3 to 4.2 +/- 0.3 a week (P < 0.001). The placebo group showed no significant change in spontaneous erections (2.4 +/- 0.3 and 2.6 +/- 0.3, respectively). The subjective parameters, however, such as libido, degree of erection, and frequency of sexual intercourse showed no significant difference within each group. There was no difference in LH, follicle-stimulating hormone, or testosterone concentrations in both groups. Thus, treatment with naltrexone significantly raises the rate of spontaneous early morning erections when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Economic analysis of sildenafil citrate (Viagra) add-on to treat erectile dysfunction associated with selective serotonin reuptake inhibitor use.

The objective of this study was to compare the economic cost of adding sildenafil citrate (Viagra, Pfizer Inc., New York, NY) to treat selective serotonin reuptake inhibitor (SSRI)-induced erectile dysfunction with that of discontinuing antidepressant pharmacotherapy, switching patients to another SSRI, or adding a non-SSRI. Based on our real-world experience in an academic medical center, we performed an economic analysis of a hypothetical cohort of 1000 patients taking SSRIs on a course of acute and continuation treatment recommended by the American Psychiatric Association. We used standard costing of antidepressants, sildenafil, and unit costs for physician visits within a managed care environment and cost-of-illness methodology to calculate the annualized cost of depression for different treatment outcomes. After 6 months of SSRI treatment, the sildenafil add-on group had the lowest cost estimates compared with groups that discontinued SSRIs, substituted another SSRI (switching), or added a non-SSRI to the existing SSRI (augmentation). Sensitivity analyses demonstrated that the physician visit was the single most important cost component in this hypothetical population and relapse/remission the most costly outcome. Sildenafil can be a cost-effective add-on therapy to control SSRI-induced erectile dysfunction. Healthcare payors should consider this when developing optimum treatment strategies for men with depression.

Antidepressive Agents↗

Association of type and duration of diabetes with erectile dysfunction in a large cohort of men.

OBJECTIVE: Differences in risk of erectile dysfunction (ED) by characteristics of diabetes among older men are not well understood. We examined the association of type and duration of diabetes with erectile function in men >50 years of age in a large prospective cohort study. RESEARCH DESIGN AND METHODS: Subjects included 31,027 men aged 53-90 years in the Health Professionals Follow-Up Study cohort. On a questionnaire mailed in 2000, participants rated their ability (without treatment) in the past 5 years to have and maintain an erection sufficient for intercourse. Men who reported poor or very poor function were considered to have ED. Diabetes information was ascertained via self-report and documented with supplementary medical data. RESULTS: Men with diabetes had an age-adjusted relative risk (RR) of 1.32 (95% CI 1.3-1.4) for having ED compared with men without diabetes. In multivariable regression analyses, men with type 1 and type 2 diabetes were at a significantly higher risk for ED (type 1 diabetes RR = 3.0, 95% CI 1.5-5.9; type 2 diabetes RR = 1.3, 1.1-1.5) than nondiabetic men. Men with type 2 diabetes had an increasingly greater risk of ED with increased duration since diagnosis (trend test P value <0.0001) (RR = 1.7, 95% CI 1.1-2.7, for men diagnosed >20 years previously). CONCLUSIONS: For men over age 50 years, increasing duration of diabetes was positively associated with increased risk of ED relative to nondiabetic subjects. This association persisted despite the higher prevalence of other comorbid conditions. ED prevention and diabetes management efforts are likely to go hand-in-hand.

Age Distribution↗

[Effectiveness of and tolerance to intracavernous injection of moxisylyte in patients with erectile dysfunction: effect/dose relationship versus placebo].

The authors investigated the optima dose (efficacy and safety) of moxisylyte, an alpha-blocking agent, in a double-blind placebo-controlled crossover study in 30 patients. The origin of the erectile dysfunction was predominantly psychological in 14 patients and neurological in 16 patients. Each patient received 4 intracavernous injections in a randomized order (placebo, 10, 20, 30 mg of moxisylyte) at 7-day intervals. Regardless of the dose, moxisylyte induced significantly greater penile responses than placebo on all erection criteria. The frequency of responses allowing sexual intercourse appeared to be dose-dependent in the two aetiological groups. The erectile responses most frequently obtained were complete rigidity in the "neurological" group and tumescence in the "psychological" group. The safety was excellent for 95.6% of injections and no case of priapism was observed. One patient (neurological patient) experienced two prolonged erections after the dose of 20 mg and another patient (psychological patient) reported 2 headaches after the dose of 30 mg. No pain was experienced on injection. Moxisylyte is very well tolerated and is able to induce an erectile response from the dose of 10 mg. This dose appears to be sufficient in patients with central neurological erectile dysfunction; a dose of 20 mg tends to improve the quality of response in patients with a predominantly psychological disorder, although the differences observed between the doses were not statistically significant in this number limited of patients.

Adult↗

Time dependent patient satisfaction with sildenafil for erectile dysfunction (ED) after nerve-sparing radical retropubic prostatectomy (RRP).

PURPOSE: The response to sildenafil after radical retropubic prostatectomy (RRP) has been reported to be approximately 40% by the Sildenafil Study Group. We undertook a study in a large cohort of post-RRP erectile dysfunction (ED) patients in order to examine the relationship between satisfaction with sildenafil and time from surgery to start of sildenafil treatment. METHODS: Pre- and post-operative erectile function was assessed by the O'Leary Brief Sexual Function Inventory questionnaire. Patient satisfaction with sildenafil before and after sildenafil treatment was assessed by the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Between April and October 1998, EDITS questionnaires were given to 579 patients who had undergone RRP between 1994 and 1998. 316 (55%) patients returned questionnaires. Of these, 198 (63%) had sildenafil treatment and completed post-treatment questionnaires and were included in the study group. RESULTS: In the study group, mean age was 61y. Pre-operatively, 92% had erections sufficient for vaginal penetration, 95% had bilateral nerve-sparing (NS) RRP. There was a significant increase in the treatment satisfaction rate with increasing time from surgery. Between zero and six months after surgery, the treatment satisfaction rate was 26%, which improved with time, peaking at 60% between 18 months and 2y. Self-perceived erectile function as determined by post-RRP pre-sildenafil treatment O'Leary questionnaires was not as predictive of response to sildenafil as time from surgery. CONCLUSIONS: The response to sildenafil appears to be dependent upon the interval between RRP and the start of sildenafil. The treatment satisfaction rate was found to peak at 60% between 18 months and 2y. Early nonresponders to sildenafil should not be disheartened, as they will more likely later respond.

Cohort Studies↗

The evaluation and management of erectile dysfunction.

Significant progress has been realized in the evaluation and treatment of erectile disorders during the past 15 years. The establishment of interdisciplinary teams and evolution of treatment centers have led to comprehensive, state-of-the-art evaluation and multiple innovative treatment options. Limitations in our knowledge, however, remain because age-related standards for diagnostic tests are not available. In some cases, we remain humble and uncertain about the validity of our diagnostic methods and our ability to offer proper treatments. The field is not standing still, however, and we expect that further refinements in evaluation techniques based on new findings in physiology and fresh psychological and medical approaches will make erectile dysfunction more efficiently and effectively treatable.

Adult↗

Sildenafil for selective serotonin reuptake inhibitor-induced erectile dysfunction in elderly male depressed patients.

Treatment with antidepressants, especially agents with potent serotonergic effects, is frequently associated with sexual side effects. In the present study, we examined the efficacy of sildenafil, a potent phosphodiesterase inhibitor, in the treatment of elderly men (n = 10; 70-81 years) with erectile dysfunction induced by antidepressant treatment for major depressive disorder. Eligible subjects were instructed to add sildenafil (25-50 mg/day) to their current drug treatment. Clinical assessment of erectile function was performed at beginning of treatment with sildenafil and at follow up, 4 weeks later. All patients reported an improvement of their erectile capacity, and in 7 out of 10 subjects, erectile function returned to a normal level. Sildenafil appears to be a safe and well-tolerated agent in elderly subjects. We noted side effects in 2 patients (flashes), but the side-effects were bothersome only to one patient (headache). It appears that sildenafil coadministration improves erectile dysfunction associated with selective serotonin reuptake inhibitor ongoing treatment in elderly patients.

Aged↗

Efficacy and safety of sildenafil citrate in men with erectile dysfunction and chronic heart failure.

Chronic heart failure (CHF) is an increasingly common cardiovascular disorder. Many patients who have CHF report moderate to marked decreases in the frequency of sexual activity, and up to 75% of patients report erectile dysfunction (ED). There are few controlled clinical data on the efficacy and safety of sildenafil citrate in men who have ED and CHF; thus, we evaluated these parameters in patients who had stable CHF. This was a double-blind, placebo-controlled, flexible-dose study. Men who had ED and stable CHF were randomized to receive sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of the International Index of Erectile Function. Secondary outcomes included the 5 functional domains of the International Index of Erectile Function, 2 global efficacy assessment questions, intercourse success rate, the Erectile Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction Checklist. By week 12, patients who received sildenafil (n = 60) showed significant improvements on questions 3 and 4 compared with patients who received placebo (n = 72; p <0.002). Larger percentages of patients who received sildenafil reported improved erections (74%) and improved intercourse (68%) compared with patients who received placebo (18% and 16%, respectively). Intercourse success rates were 53% among patients who received sildenafil and 20% among those who received placebo. Patients who received sildenafil were highly satisfied with treatment and their sexual life compared with patients who received placebo. Sixty percent of patients who received sildenafil and 48% of patients who received placebo developed adverse events, including transient headache, facial flushing, respiratory tract infection, and asthenia. The incidence of events related to cardiovascular effects was low. Sildenafil is an effective and well-tolerated management of ED in men who have mild to moderate CHF.

Adult↗

[Open multicenter study of the differential diagnosis of erectile dysfunction with a papaverine-phentolamine combination (BY023)].

We report the results of an open multicenter clinical trial with 115 patients. The results of a pharmacological test using intracavernously applied mixture of papaverine and phentolamine were compared with the results of a multidisciplinary evaluation of erectile dysfunction. Sensitivity and specificity of our test were determined. The injection of our drug solution caused an increase in tumescence and/or rigidity in all patients. The evaluation of the dose dependent erectile response makes it possible to distinguish between the three main pathogenetic principles: non-vascular, arterial and venous etiology of erectile dysfunction. The pharmacological test requires one to four intracavernous injections of 0.5-3.0 ml of the drug solution (7.5-45 mg papaverine hydrochloride, 0.25-1.5 mg phentolamine mesylate).

Adolescent↗

[Erectile dysfunction. Are interdisciplinary diagnosis and therapy necessary?].

OBJECTIVE: The last few decades have seen a marked increase in mean life expectancy in Central Europe. This has made elderly people and their quality of life a matter of ever-increasing medical concern. Besides the lack of population based studies in Central Europe, the identifying risk factors for the development of erectile dysfunction (ED) is crucial. METHODS AND MATERIAL: A newly developed and validated questionnaire on male erectile dysfunction was mailed to a representative population sample of 8000 men 30 to 80 years of age in the Cologne urban district. RESULTS: The response included 4489 analysable replies (56,1 %). The median age was 51,8 years. Prevalence of ED was estimated at about 19.2 %, with a steep age-related increase (2,3 - 53,4 %) Therapeutic necessity (defined by co-occurrence of ED and dissatisfaction with sex life), also increases with age. The overall number of ED sufferers seeking therapy was 6,8 %. The following illnesses where seen in the ED group: heart failure (14,7 %), pelvic surgery (18,8 %), diabetes mellitus (20,2 %), peripheral arterial circulatory disorders (21,5 %), herniated disc (23,2 %) and hypertension (32,0 %). Although the pathogenetic pathway remains unclear with a prevalence of 72 % "lower urinary tract symptoms" (LUTS) seems to be an age independent risk factor. In contrast, the prevalence of ED in healthy men was around 6,6 %. CONCLUSIONS: ED is a common disorder, contributing to dissatisfaction with sex life in a considerable proportion of men. ED is frequently associated with chronic diseases. For this reason adequate interdisciplinary diagnostic workup is essential, to offer patients individually adapted treatment.

Adrenergic beta-Antagonists↗

[Functional electromyostimulation of the penile corpus cavernosum (FEMCC)]. Initial results of a new therapeutic option of erectile dysfunction].

Transcutaneous application of low-frequency electric current in the treatment of partially or temporarily denervated striated muscles is widely used to prevent or treat muscular atrophy. Due to the high regenerative capacity of smooth muscle cells, this approach should be beneficial in the treatment of diseases with smooth muscle degeneration due to partial denervation. Our study was done to evaluate the possible beneficial effect of transcutaneous application of low-frequency electric current to the corpus cavernosum penis in the treatment of erectile dysfunction. After a comprehensive work-up, 22 patients with chronic erectile dysfunction (21/22 vasoactive nonresponders) received daily (3-5 x 20 min) transcutaneous functional electromyostimulation of the corpus cavernosum smooth muscles (FEMCC; zero line symmetric impulses of trapezoid shape, two-channel device with alternating stimulations, f = 10-20 Hz for channel I and 20-35 Hz for channel II; t(i) = 100-2000 microseconds, approx. 12 mA, rise time 0.5 s, stimulation time 5 s per channel, interval between stimulations 0.5 s). Five of 22 patients (23%) regained full spontaneous erections and another three (14%) responded to vasoactive drugs after FEMCC. Fourteen were FEMCC failures, including two who subjectively 'improved'. In a similar group of patients evaluated during the same period but receiving no therapy, no spontaneous improvement of the erectile function was observed. Our preliminary results suggest that FEMCC is feasible and results in an improvement of the erectile capacity in a significant proportion (37%) of patients. Further studies will be carried out to corroborate our results, to improve stimulation parameters and to evaluate selection criteria for FEMCC.

Adult↗

Psychiatric morbidity is frequently undetected in patients with erectile dysfunction.

PURPOSE: We investigated the prevalence of psychiatric morbidity in patients with erectile dysfunction (ED). MATERIALS AND METHODS: Consecutive patients who attended an andrology outpatient clinic complaining of ED were recruited for study purposes. ED severity was evaluated by the International Index of Erectile Function erectile function domain score. The psychiatric diagnosis was established by a semistructured clinical interview as well as by the Mini International Neuropsychiatric Interview 5 Diagnostic and Statistical Manual of Mental Disorders-IV. The Beck Depression Inventory was also incorporated as a complementary tool to assess depressive symptom severity. RESULTS: The study included 103 patients 20 to 76 years old (mean age +/- SD 47.06 +/- 14.78) with ED. Most patients were classified with moderate and severe ED (26.2% and 44.7%, respectively). A detectable psychiatric condition was present in 63.1% of the patients, including depressive disorders in 25.2%, anxiety disorders in 11.7%, depression-anxiety comorbidity in 6.8% and personality disorders in 5.8%. A positive psychiatric anamnesis was identified in 41 cases, while 24 were newly diagnosed. No significant association was found between the duration and severity of ED, and psychiatric morbidity or the severity of depressive symptoms (p > 0.05). A positive association was found between the severity of depressive symptoms and the patient tendency to discuss the problem with their partner (p < 0.01). CONCLUSIONS: Psychiatric morbidity is highly prevalent in patients with ED, potentially affecting treatment outcome. Because lifetime psychological problems were reported by more than half of the patients, a psychosocial history seems mandatory. Partner support appeared to have a significant role in the patient psychological state.

Adult↗

Vardenafil increases penile rigidity and tumescence in erectile dysfunction patients: a RigiScan and pharmacokinetic study.

The pharmacodynamic effect on penile rigidity and tumescence and the pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil, a new PDE5-inhibitor, were investigated in 21 erectile dysfunction patients. Patients were evaluated with RigiScan on three occasions in a randomized, placebo-controlled, double-blind crossover fashion, while receiving visual sexual stimulation. Relative to placebo, a single dose of 10 mg vardenafil led to a mean increase in the duration of >60% penile rigidity of 24.4 min (95% CI: 7.4 to 41.3) at the base and of 24.8 min (8.5 to 41.1) at the tip. For the 20-mg dose, the increase in duration of > 60% penile rigidity relative to placebo was 37.2 min (20.2 to 54.1) at the base and 28.7 min (12.7 to 44.7) at the tip. Single doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations of vardenafil, with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of 9.1 microg/l (geometric SD = 1.63) and 20.9 microg/l (geometric SD = 1.83), respectively. In the post-absorptive phase, the concentrations declined with an average terminal t 1/2 of 4.2 h (geometric SD = 1.27) and 3.9 h (geometric SD = 1.31). The systemic exposure of vardenafil expressed as AUC normalized for dose and body weight was dose-proportional (associated 90% CI: -4 to 30%) as well as Cmax (associated 90% CI: -12 to 33%). The treatments were well tolerated. There was a small, clinically irrelevant reduction in blood pressure with a small compensatory rise in heart rate. There were no electrocardiographic effects or relevant changes of the safety laboratory screens. The observed pro-erectile properties, pharmacokinetic characteristics and safety profile make vardenafil a suitable candidate for further evaluation in the treatment of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗