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Vardenafil increases penile rigidity and tumescence in men with erectile dysfunction after a single oral dose.

OBJECTIVES: To evaluate the effect of two doses of vardenafil hydrochloride on penile rigidity and tumescence while determining the pharmacokinetics. METHODS: Twenty-one patients with erectile dysfunction completed three oral single-dose regimens (placebo, 20 and 40 mg vardenafil) in a randomized, placebo-controlled, 3-way cross-over study. Penile rigidity and tumescence were measured at the base and tip with a Rigiscan for up to 2 h after dosing. The period included three 20-min repeated episodes of visual sexual stimulation. Blood samples were taken periodically up to 24 h after dosing. RESULTS: After 20 and 40 mg vardenafil, the mean duration of >60% rigidity of the base of the penis was greater than after placebo by 42.9 min (95% Cl 29.3-56.4) and by 49.3 min (95% Cl 35.7-62.9), respectively (p<0.001), and greater than after placebo by 34.6 min (95% Cl 22.1-47.1) for both doses at the tip. Additionally, significantly greater rigidity activity units and tumescence activity units were found for both doses compared with placebo (p<0.001). The plasma concentrations of vardenafil increased rapidly, with a median t(max) of about 40 min and a mean t1/2 of 4.4-4.8 h. Relative bioavailability was slightly higher for the 40-mg dose than for the 20-mg dose. The treatments were well tolerated, although slightly more adverse events, primarily headache, flushing and nasal congestion, were seen with the 40-mg dose compared with placebo. CONCLUSION: The findings confirm that vardenafil was able to generate stronger erections of longer duration than placebo under conditions of visual sexual stimulation in patients with erectile dysfunction. The pharmacokinetic, pharmacodynamic and tolerability profiles support vardenafil hydrochloride as a strong candidate for further testing as a treatment for erectile dysfunction.

Adolescent↗

Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials.

AIMS/HYPOTHESIS: A retrospective analysis of pooled data from twelve placebo-controlled trials was conducted to characterise the efficacy and safety of tadalafil for the treatment of erectile dysfunction in men with diabetes compared with that in men without diabetes. METHODS: Patients were randomly allocated to tadalafil 10 mg, 20 mg, or placebo, taken as needed for 12 weeks. The study population comprised 637 men with diabetes (mean age 57 years) and 1681 men without diabetes (mean age 56 years). RESULTS: At baseline, patients with diabetes had more severe erectile dysfunction than patients without diabetes, with mean International Index of Erectile Function (IIEF) erectile function domain scores of 12.6 and 15.0 respectively (p<0.001). Compared with placebo, tadalafil 10 mg and 20 mg improved all primary efficacy outcomes in both patient groups (p<0.001). Men with diabetes receiving tadalafil 20 mg experienced a mean improvement of 7.4 in their IIEF erectile function domain score against baseline versus 0.9 for placebo (p<0.001). This group reported on average that 53% of their attempts at intercourse were successful, compared with 22% for placebo (p<0.001 for the change from baseline). Baseline IIEF erectile function domain scores correlated inversely with baseline HbA(1)c levels. The responses to tadalafil were similar regardless of levels of baseline glycaemic control, diabetic therapy received, or previous use of sildenafil. CONCLUSIONS/INTERPRETATION: Despite more severe baseline erectile dysfunction in men with diabetes, tadalafil was efficacious and well tolerated in this population. As reported for other phosphodiesterase 5 inhibitors, the response to tadalafil was slightly lower in men with diabetes than in men without diabetes.

Blood Glucose↗

[Effectiveness and adverse effects of sildenafil in erectile dysfunction].

Sildenafil is a selective and by oral administration potent type-5 phosphodiesterase (PDE 5) inhibitor, which increases the erection by corpus cavernosum smooth muscle relaxation. In a non-placebo controlled study, 134 patients with erectile dysfunction were treated with oral sildenafil. The aim of the study was to estimate the efficacy and adverse effects of this treatment. 51 patients (38%) had psychogenic, and 83 (62%) organic origin of the erectile dysfunction. 73 of them have already had some treatment for this problem before. The effective dose was 50 mg for 84 patients (63%), 100 mg for 32 (24%) and 25 mg for 4 patients. The treatment was effective for 120 patients (90%). The most common adverse effect was flushing in 18 (13%) and headache in 9 (7%) cases, two patients had headache and flushing together. Nasal congestion and visual disturbances were complained by two patients. Two patients reported prolonged (max. 2h) erections. Cardiological investigation was performed for cardiovascular patients and for patients with risk factors. Exact criteria of the cardiological opinion of sildenafil treatment are reviewed. Cardial or other serious adverse effects were not observed. It was not necessary to stop the treatment because of the adverse effects. The authors found, that sildenafil is an effective and safe treatment for the erectile dysfunction.

Adult↗

Thalassaemic men affected by erectile dysfunction treated with transurethral alprostadil: case report.

The aim of this controlled clinical study, performed in a specialized institutional unit for thalassaemic men, was to consider the possibility of restoring erection in beta-thalassaemic patients with erectile dysfunction by administering E(1) prostaglandins (alprostadil) transurethrally. Four patients affected by beta-thalassaemia, aged between 32 and 52 years, and having an erectile dysfunction were included in the study. Each patient was given 500 microg alprostadil in the distal urethra. Response was evaluated by the erection assessment scale. The main outcome measures were: (i) the clinical study; (ii) FSH, LH, total and free testosterone plasma concentrations; and (iii) basal and dynamic Doppler sonography of cavernous arteries. The treatment produced a response of 3-4 on the erection assessment scale. Average minimum response time was 20 min, while average maximum response time was about 60 min. There was no evidence of significant side effects. Our hypothesis is that the delayed reaction was due to organ damage induced by iron load, causing a reduction or absence of elasticity in the interstitial tissue of the corpora cavernosa. Thus, we believe that treatment with alprostadil can be considered an effective, non-invasive therapy for thalassaemic patients with erectile dysfunction.

Adult↗

[Pathophysiology and rehabilitation of erectile dysfunction after nerve-sparing radical prostatectomy].

Radical prostatectomy is the current standard procedure for locally confined prostate cancer and accounts for the largest portion of invasive therapies. However, a major drawback of this approach remains the frequently ensuing postoperative erectile dysfunction. This aspect represents a frequent cause of fear and concern both for the patients and their partners and has a significant impact on the choice of therapy.After bilateral sparing of the neurovascular bundles, an average of 50% of the patients is likely to complain of erectile dysfunction. It is only in the course of the first 2 years after prostatectomy that rehabilitation of erectile dysfunction can be expected. It is all the more crucial to begin with rehabilitation therapy of the erectile tissue at an early postoperative stage to the prevent an irretrievable loss of erectile function. Application of PDE-5 inhibitors as well as prostaglandins, phentolamine, or papaverine can help to induce and to support penile blood perfusion and oxygenation, thus preserving structure and function of the corpora cavernosa. All efforts must be directed towards keeping the erectile function at the level ascertained prior to the intervention.

Clinical Trials as Topic↗

[Treatment of erectile dysfunction after nerve-preserving radical retropubic prostatectomy].

The aim of the study was evaluation of erectile function (EF) recovery and effects of PDE-5 inhibitor tadalafil in the treatment of erectile impairment one year after conduction of nerve-preserving retropubic radical prostatectomy (RRP). Thirty patients with intact EF before surgery who had RRP were divided into two groups. In 18 patients of group I vasculonervous fascicles (VNF) were preserved on both sides. A unilateral nerve-preserving technique was used in 12 patients of group 2. Tadalafil administration was started 3 months after operation in the dose 20 mg. In group I partial erection was observed in 11 patients, was absent in 33% (6 patients), a complete erection was in one (6%) patient. Thus, 67% (12 patients) could maintain erection sufficient for coitus. Out of 12 patients of group 2, a complete erection was achieved in none patients, partial erection was observed in 5 (42%) patients, erection did not occur in 7 (58%) patients. Thus, EF is better in patients with bilateral preservation of VNF than in unilateral one. Pharmacotherapy of erectile dysfunction after nerve-preserving RRP is most effective. It is desirable to adhere to early postoperative policy in the treatment of EF. PDE-5 inhibitors are rather effective if the patient has a partial erection. They fail in the absence of spontaneous erections. Early therapy prevents subsequent progression of erectile dysfunction.

Aged↗

Increased expression of arginase II in human diabetic corpus cavernosum: in diabetic-associated erectile dysfunction.

Nitric oxide (NO) is the principal mediator of penile erection. NO is synthesized by nitric oxide synthase (NOS). It has been well documented that the major causative factor contributing to erectile dysfunction in diabetic patients is the reduction in the amount of NO synthesis in the corpora cavernosa of the penis resulting in alterations of normal penile homeostasis. Arginase is an enzyme that shares a common substrate with NOS, thus arginase may downregulate NO production by competing with NOS for this substrate, l-arginine. The purpose of the present study was to compare arginase gene expression, protein levels, and enzyme activity in diabetic human cavernosal tissue. When compared to normal human cavernosal tissue, diabetic corpus cavernosum from humans with erectile dysfunction had higher levels of arginase II protein, gene expression, and enzyme activity. In contrast, gene expression and protein levels of arginase I were not significantly different in diabetic cavernosal tissue when compared to control tissue. The reduced ability of diabetic tissue to convert l-arginine to l-citrulline via nitric oxide synthase was reversed by the selective inhibition of arginase by 2(S)-amino-6-boronohexanoic acid (ABH). These data suggest that the increased expression of arginase II in diabetic cavernosal tissue may contribute to the erectile dysfunction associated with this common disease process and may play a role in other manifestations of diabetic disease in which nitric oxide production is decreased.

Arginase↗

Erectile dysfunction: current concepts and future directions.

Major advances in science and medicine have led to improved understanding of the pathophysiology of erectile dysfunction. The development of reliable pharmacological therapy for erectile dysfunction has led to heightened awareness in the public and medical communities. This article reviews recent clinical advances and future research directions.

Erectile Dysfunction↗

Treatment of postpriapism erectile dysfunction by closure of persistent distal glans-cavernosum fistulas 5 years after shunt creation.

Erectile dysfunction is common after the formation of a glans-cavernosum shunt for intractable priapism. Often patients require placement of a penile prosthesis to restore sexual function. We report a case of restoration of full erections after reversal of a glans-cavernosum shunt in a 30-year-old man who had been treated for priapism 5 years previously. On the basis of our experience, it seems reasonable to attempt shunt reversal for correction of erectile dysfunction in selected patients who likely have a persistent vascular fistula.

Adult↗

Bladder and erectile dysfunction before and after rectal surgery for cancer.

OBJECTIVE: To establish the incidence of bladder and erectile dysfunction after rectal surgery for cancer. PATIENTS AND METHODS: Twenty patients (16 men and four women, median age 66 years, range 36-78) with carcinoma of the rectum were prospectively studied immediately before and 4 months after operation by clinical assessment, uroflowmetry and video-cystometrography. All patients were catheterized routinely at the time of surgery. Those experiencing voiding difficulties after catheter removal were managed by intermittent self-catheterization or an indwelling urethral catheter. RESULTS: Before surgery, only six patients had completely normal bladder function and 13 of the 16 men were at least partially potent. Eight of the 19 patients who eventually had surgery developed identifiable bladder dysfunction, of whom three had urodynamic evidence of complete bladder denervation. Three men who were potent before became impotent after surgery. CONCLUSIONS: Bladder and erectile dysfunction are recognized complications of radical rectal surgery, although there is significant variation in the reported risk; much of this variability is related to the retrospective nature of most previous studies. This study demonstrates the importance of prospective urodynamic evaluation and confirms that the small but significant risk of permanent bladder dysfunction is likely to be related to pelvic nerve injury at the time of surgery.

Adult↗

A study in patients with erectile dysfunction comparing different formulations of prostaglandin E1. Alprostadil Study Group.

PURPOSE: Prostaglandin E1 sterile powder and sterile solution are 2 new formulations of exogenous prostaglandin E1 that are more convenient for auto-injection therapy for erectile dysfunction than the presently used pediatric sterile solution. Therefore, the pharmacodynamic profiles of intracavernous prostaglandin E1 sterile powder and nonalcohol sterile solution were compared with the pediatric sterile solution in men with erectile dysfunction who were known to be stable responders to intracavernous prostaglandin E1. MATERIALS AND METHODS: Based on the dose used at home, patients were randomized to 1 of 5 dose groups: 0 microgram. (placebo), 2.5 micrograms., 5 micrograms., 10 micrograms. or 20 micrograms. Each patient received a single injection of the same dose of each of the 3 formulations. The primary pharmacodynamic end points were clinical evaluation of erectile response, RigiScan real-time evaluation of erectile response and patient evaluation of erectile response. RESULTS: No significant differences were identified among the formulations for any of these end points, either by comparison among all active doses or by comparison at each prostaglandin E1 dose level. There was also little or no intra-patient variation in dose response and the inter-dose variation in response between patients was not significant. Pharmacodynamic end points were well intercorrelated, although assessment of erectile response by the patients tended to be more positive than that by RigiScan or clinical evaluation. There were no major side effects. Penile pain on injection and/or during erection occurred in 9 to 17% of the patients according to the formulations. However, penile pain was also reported by 11% of the placebo-treated patients. CONCLUSIONS;: The 3 formulations of prostaglandin E1 showed equivalence and were safe for the treatment of erectile dysfunction with respect to side effects.

Alprostadil↗

Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial.

CONTEXT: Healthy lifestyle factors are associated with maintenance of erectile function in men. OBJECTIVE: To determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial of 110 obese men (body mass index > or =30) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function (IIEF). The study was conducted from October 2000 to October 2003 at a university hospital in Italy. INTERVENTIONS: The 55 men randomly assigned to the intervention group received detailed advice about how to achieve a loss of 10% or more in their total body weight by reducing caloric intake and increasing their level of physical activity. Men in the control group (n = 55) were given general information about healthy food choices and exercise. MAIN OUTCOMES MEASURES: Erectile function score, levels of cholesterol and triglycerides, circulating levels of interleukin 6, interleukin 8, and C-reactive protein, and endothelial function as assessed by vascular responses to l-arginine. RESULTS: After 2 years, body mass index decreased more in the intervention group (from a mean [SD] of 36.9 [2.5] to 31.2 [2.1]) than in the control group (from 36.4 [2.3] to 35.7 [2.5]) (P<.001), as did serum concentrations of interleukin 6 (P =.03), and C-reactive protein (P =.02). The mean (SD) level of physical activity increased more in the intervention group (from 48 [10] to 195 [36] min/wk; P<.001) than in the control group (from 51 [9] to 84 [28] min/wk; P<.001). The mean (SD) IIEF score improved in the intervention group (from 13.9 [4.0] to 17 [5]; P<.001), but remained stable in the control group (from 13.5 [4.0] to 13.6 [4.1]; P =.89). Seventeen men in the intervention group and 3 in the control group (P =.001) reported an IIEF score of 22 or higher. In multivariate analyses, changes in body mass index (P =.02), physical activity (P =.02), and C-reactive protein (P =.03) were independently associated with changes in IIEF score. CONCLUSION: Lifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline.

Adult↗

[Prostaglandin E1 (PGE1) in diagnosis and long-term therapy of erectile dysfunction].

The aim of this retrospective study was to determine the worth of prostaglandin E1 (PGE1) for the diagnosis and therapy of erectile dysfunction using the study of documents, a questionnaire and a clinical control. In testing, 58.3% of 300 patients responded completely to PGE1. Complications were pain (13%) and prolonged erections of more than 3 h (5%). Sixty-four of 300 patients began continuous therapy. Forty-three of 64 patients were evaluated retrospectively (time 5/88-9/94). Nine of 43 primary patients and 16/34 secondary patients dropped out after a medium therapy of 1 year. The main reasons for the dropouts were pain and fear of complications related to the therapy. Complications in long-term therapy were pain (35.3%), prolonged erection (0.4%), and local fibrosis (5.9%). PGE1 is not a magic drug in erectile dysfunction. The advantage of fewer prolonged erections compared to papaverine/phentolamin is restricted by the high incidence of pain. The relative lack of acceptance of autoinjection therapy in long-term follow-up demonstrates its limited value in the therapy of erectile dysfunction.

Alprostadil↗

Routine psychophysiological screening of 384 men with erectile dysfunction.

Psychophysiological screening was carried out on 384 consecutive patients with erectile dysfunction of psychogenic or psychogenic-organic origin. Visual sexual stimulation with penile vibration caused a satisfactory erection in roughly 50% of patients. Nonresponders subsequently produced a good penile response with intracavernous injection of vasoactive substance. Orgasm-ejaculation can occur in the absence of a full erection. In such cases subsequent intracavernous injection brought about a (near) full erection. A first intracavernous injection was most effective when combined with visual and vibrotactile stimulation. The magnitude of the response to such stimulation is useful to enable the doctor to prescribe the lowest dose of a vasoactive substance, thus minimizing the risk of priapism. Preferably, drug treatment of men with erectile dysfunction should be combined with sexual counseling or therapy.

Adult↗

The effect of topically applied vasoactive agents and testosterone versus testosterone in the treatment of erectile dysfunction in aged men with low sexual interest.

The objective was to evaluate the efficacy and safety of topically applied cream containing testosterone, isosorbide dinitrate and co-dergocrine mesylate compared to testosterone cream in the treatment of erectile dysfunction in aged men with low sexual interest. A randomised double-blind crossover trial was performed over two months. The subjects were 42 men with erectile dysfunction and low normal or slightly depressed testosterone level randomly allocated to two equal groups. Polypharmacy cream containing testosterone 0.8%, isosorbide dinitrate 0.5% and co-dergocrine mesylate 0.06% was applied for one month, and testosterone 0.8% cream for another month. The serum level of total testosterone was measured before and after each phase of treatment. Response to each therapy was assessed by a sexual questionnaire, measurement of tumescence and repeat penile duplex ultrasonography. Twenty-eight patients reported full erection and satisfactory intercourse with the polypharmacy cream. Thirteen men reported full erection and satisfactory intercourse with either cream. Polypharmacy cream increased penile arterial flow (P<0.001) and induced tumescence in 34 patients in lab. No patient in either phase of the study has tumescence or a significant increase in cavernous arterial peak systolic velocities after the application of testosterone cream. Serum level of total testosterone increased in all patients (P<0.05). Sexual desire was improved in 85% and 62% of patients during the treatment with polypharmacy cream and testosterone cream, respectively. No marked side effects were reported after either of them. Topical treatment with cream containing testosterone and vasoactive agents may represent a new effective treatment for erectile dysfunction associating with aging.

Administration, Topical↗

Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra).

OBJECTIVES: To determine whether the response to the new oral medication, sildenafil citrate (Viagra), was influenced by the presence or absence of the neurovascular bundles, as recent reports on its success did not specify the efficacy of the drug in patients with erectile dysfunction after radical prostatectomy. METHODS: Baseline and follow-up data from 28 healthy patients presenting with erectile dysfunction after radical prostatectomy were obtained. Patients receiving any neoadjuvant/adjuvant hormones or adjuvant radiation therapy were excluded. Patients reported what their erectile status was before surgery, before sildenafil therapy, and after using a minimum of four doses of sildenafil. Both the patients and their spouses were interviewed using the Cleveland Clinic post-prostatectomy questionnaire, which includes questions about response to therapy, duration of intercourse, spousal satisfaction, side effects, and related topics. The patients were compared on the basis of the type of surgical procedure they had undergone-nerve sparing or non-nerve sparing. A positive response to sildenafil was defined as erection sufficient for vaginal penetration. RESULTS: Of the 15 patients who had bilateral nerve-sparing procedures, 12 (80%) had a positive response to sildenafil, with a mean duration of 6.92 minutes of vaginal intercourse. These 12 patients also reported a spousal satisfaction rate of 80%. All 12 of the responders had a positive response within the first three doses, and 10 of the 12 responded with the first or second dose. None of the 3 patients who had undergone a unilateral nerve-sparing procedure responded, nor did any of the 10 patients who had undergone a non-nerve-sparing procedure. The two most common side effects of the drug were transient headaches (39%) and abnormal color vision (11%). No patients discontinued the medication because of side effects. CONCLUSIONS: Successful treatment of erectile dysfunction in a patient after prostatectomy with sildenafil citrate may depend on the presence of bilateral neurovascular bundles. No patient who had undergone a non-nerve-sparing procedure responded. Whether patients who undergo unilateral nerve-sparing procedures will respond to sildenafil is still unclear because of the small number of patients in our study. These findings should encourage urologists to continue to perform and perfect the nerve-sparing approach. The ability to restore potency with an oral medication after radical prostatectomy will impact our discussion with the patient on the surgical morbidity of radical prostatectomy.

Enzyme Inhibitors↗

New treatment for erectile dysfunction.

Numerous advances have been made in our understanding of the evaluation and treatment of erectile dysfunction. Numerous treatment options are currently available. Treatment of this disorder was revolutionized by the introduction of sildenafil, an oral vasoactive agent that has a peripheral mechanism of action, blocking the degradation of cyclic guanosine monophosphate, and thus augmenting the erectogenic effect of sexual stimulation. This agent has proven efficacy in a variety of patient populations, including psychiatric patients. Clinical series suggest that this agent will reverse erectile dysfunction induced by psychoactive agents. Thus, it may play a role in decreasing treatment noncompliance associated with drug-induced sexual dysfunction. Another novel agent that is in development may be of special interest to psychiatrists. Apomorphine is a central dopamine agonist that is believed to act at the level of the paraventricular nucleus of the hypothalamus. As new agents are evolving, our understanding of the neurobiology of sexual function is advancing.

Apomorphine↗