Amado Bechara

Comparative Efficacy Assessment of Tamsulosin vs. Tamsulosin Plus Tadalafil in the Treatment of LUTS/BPH. Pilot Study

INTRODUCTION The high incidence of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in aging men and the same pathophysiology make probable to treat both disorders with the same treatment. Numerous authors evaluated the actions of PDE5i in improving the LUTS/(benign prostate hyperplasia) BPH. AIM To assess the efficacy and safety of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day in patients with LUTS in a crossover design study. MAIN OUTCOMES MEASURES International Prostate Symptoms Score (IPSS), IPSS Quality of Life (IPSS-QOL), maximum flow rate (Qmax), post-void residual volume (PVR), International Index of Erectile Function-Erectile Function Domain (IIEF-EF), Global Assessment Quality (GAQ). For the statistical analysis, a Tukey-Kramer multicomparison test was used. METHODS A randomized, double-blind, crossover study was conducted from September 2007 to February 2008 in one center. Thirty men, older than 50 years old, with a history of LUTS/BPH of at least 6 months, were randomized into two groups to receive tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus tadalafil 20 mg/day for 45 days, and then switched to the other treatment mode for other 45 days. RESULTS Twenty-seven patients completed the study. Improvements of IPSS score and IPSS-QOL were significant with both treatments but greater with the drug combination. Both regimens similarly improved the Qmax and decreased the PVR volume from baseline (P < 0.001) with no significant differences between tamsulosin alone vs. tamsulosin and tadalafil (P > 0.05). The IIEF improved with tamsulosin plus tadalafil (P < 0.001) but not with tamsulosin alone (P > 0.05). The GAQ showed that all patients preferred the combination scheme. Both treatments were well tolerated. CONCLUSION; Tamsulosin 0.4 mg/day plus tadalafil 20 mg/day was more effective than tamsulosin 0.4 mg/day alone to improve LUTS and erectile dysfunction and was also well tolerated. Large-scale, randomized, placebo-controlled studies are needed to further assess the long-term safety and effectiveness of these agents in treating LUTS/BPH with or without ED.

Recreational use of phosphodiesterase type 5 inhibitors by healthy young men.

INTRODUCTION In recent years, PDE5 inhibitors (PDE5i) use has become more popular among men without ED to enhance sexual performance. However, reports in the literature are scarce. AIM The aim of this study was to evaluate the recreational use of PDE5i in healthy young men. MAIN OUTCOME MEASURES We evaluated the recreational use of PDE5i among young and healthy men, their main reasons for use, how they were obtained these drugs, and the combination with alcohol or other drugs. METHODS Descriptive, transversal study consisting in 400 brief surveys with structured multiple choice and open questions. Nonprobability samples (quota samples) included young men between 18 and 30 years of age in a public area (high schools, universities, and gyms) between August and November 2009. Collecting the questionnaires in a sealed box enforced confidentiality. The survey included demographic and sexual health data and PDE5i use characteristics. For statistical analysis we used Fishers exact and Mann-Whitney tests. RESULTS A total of 321 questionnaires were appropriate for the purposes of evaluation. Mean age and standard deviation were 25.1±3.3 years old. Regarding PDE5i use, 69 men (21.5%) mentioned trying the pill (being sildenafil the most commonly used one) at least one time in their lives and 37 (53.4%) men combined it with alcohol or drugs. Referred sources of acquisition PDE5i were 75.4% (N=52) from a friend, 17.4% (N=15) from a pharmacy/drugstore without a medical prescription, 4.3% (N=3) prescribed by a physician and 2.9% (N=2) through Internet. There were several reasons for taking PDE5i related to sexual confidence, erection quality, and better sexual performance. CONCLUSION According to our results, 21.5% of healthy men between 18 and 30 years old used PDE5i as a recreational drug, mostly associated with alcohol or other drugs without medical control. This could have led to misuse and a public health problem. Further studies are needed to evaluate not only PDE5i recreational use prevalence, but also psychosocial determinants, long term safety, misuse, and abuse related to it.

Prostaglandin E1 Versus Mixture of Prostaglandin E1, Papaverine and Phentolamine in Nonresponders to High Papaverine Plus Phentolamine Doses

PURPOSE We evaluated the efficacy of 40 micrograms/ml, prostaglandin E1 versus a combination of 17.64 mg./ml. papaverine hydrochloride, 0.58 mg./ml. phentolamine mesylate and 5.8 micrograms/ml. prostaglandin E1 (3-drug mixture). MATERIALS AND METHODS A total of 32 patients randomly received 1 ml. of either medication by the intracavernous route. All patients had presented with erectile dysfunction longer than 6 months in duration and had failed to respond to high doses of papaverine (60 mg.) plus phentolamine (1 mg). RESULTS Of 32 patients 7 (22%) responded to prostaglandin E1 and 16 (50%) to the 3-drug mixture, achieving erections allowing penetration (grade E4 or E5, p < 0.05). Pain was reported by 41% of the patients receiving prostaglandin E1 and 12.5% administered the 3-drug mixture. CONCLUSIONS The 3-drug mixture may be regarded as more effective than prostaglandin E1 alone in inducing an erectile response with a decreased incidence of pain.

Clitoral Hemodynamic Changes after a Topical Application of Alprostadil

We performed duplex ultrasonography of the clitoris to assess the local hemodynamic changes after a topical application of alprostadil. Color duplex ultrasonography was used to evaluate 18 women before and after the application of 1 g of 0.2% alprostadil gel. The peak systolic velocity and end diastolic velocity showed a statistically significant difference after the application. All women showed labial and clitoral engorgement, 72% reported a pleasant sensation of warmth, and no systemic side effects were found. These findings are similar to the values reported after sexual stimulation, indicating that topical vasoactive drugs might help in the differential diagnosis of the vascular component of female sexual dysfunction.

Comparative Study of Papaverine Plus Phentolamine Versus Prostaglandin E1 in Erectile Dysfunction

PURPOSE We compared the efficacy and short-term adverse effects of 1 ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine versus 1 ml. 30 micrograms./ml. prostaglandin E1 in patients undergoing pharmacological erection testing. MATERIALS AND METHODS A total of 60 patients (mean age 58 years) with a history of sexual erectile dysfunction longer than 6 months was randomly classified into 6 groups to be tested 1 week apart with the 2 solutions and with placebo to evaluate erection response and short-term adverse effects. RESULTS Of the patients tested with papaverine plus phentolamine 54% responded with erections adequate for penetration, compared to 50% of those tested with prostaglandin E1 (p > 0.05). Prolonged erection occurred in 18% of patients tested with papaverine plus phentolamine and 15% of those tested with prostaglandin E1 (p > 0.05). Pain was reported by 15 and 35% of patients, respectively (p < 0.05). CONCLUSIONS One ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine has the same efficacy and equal prolonged erection rate as 1 ml. 30 micrograms./ml. prostaglandin E1 but the latter agent induces significantly more pain.

Risk factors of Peyronie's disease. What does our clinical experience show?

INTRODUCTION Peyronies disease (PD) is a localized fibrosis that affects the tunica albuginea of the penis. Its origin can be associated with coital penile trauma in men with autoimmune hypersensitivity and a presumed genetic predisposition. AIM To identify clinical and traumatic risk factors in a patient population with PD, when compared to a control group. METHODS From November 2007 to March 2010, 317 patients sought medical attention for PD. As control group, 147 consecutive patients, who came for a prostate exam, were studied. Clinical, traumatic, and sexual history of these patients was gathered. Risks factors were considered only if they had been present before the onset of PD symptoms. MAIN OUTCOME MEASURE The International Index of Erectile Function and the International Prostate Symptoms Score. A univariate logistic regression model (chi-square) (odds ratios [ORs] and 95% confidence intervals [CI]) was used to estimate the association of risk factors with PD; and the Students t-test was implemented for age. RESULTS The mean age of patients with PD and control group was 56.7 and 58.8, respectively (P<0.923). The mean evolution time of the disease was 17.7 months (2-48). Erectile dysfunction (ED) and coital trauma constituted the only two independent risk factors for PD compared to the control group (P<0.05 and 0.002, respectively) with an OR of 1.5 (95% CI 1.0-2.3) and 2.69 (95% CI 1.41-5.21), respectively. Patients with ED and diabetes mellitus and with a mild-to-moderate ED also presented a higher predisposition (P=0.008 and 0.00001), with an OR of 3.64 (95% CI 1.33-10.79) and 5.58 (95% CI 3.03-10.42), respectively. CONCLUSION Erectile dysfunction and coital trauma have proven to be independent risk factors for the development of PD.

Twelve-Month Efficacy and Safety of Low-Intensity Shockwave Therapy for Erectile Dysfunction in Patients Who Do Not Respond to Phosphodiesterase Type 5 Inhibitors

Introduction Low-intensity shockwave therapy (LISWT) has recently emerged as a promising method in the treatment of erectile dysfunction (ED). Aim To assess the long-term results of the effectiveness and safety of LISWT in patients with ED who are non-responders to phosphodiesterase type 5 inhibitor (PDE5i) treatment. Methods This open-label, longitudinal, and observational study investigated an uncontrolled population of 50 consecutive patients whose ED was unresponsive to PDE5i treatment. Patients were treated with a four-session LISWT protocol. During active treatment and follow-up, all patients remained on their regular high on-demand or once-daily PDE5i dosing schedules. Main Outcome Measures Effectiveness was assessed according to the International Index of Erectile Function erectile function domain, questions 2 and 3 of the Sexual Encounter Profile, Erection Hardness Scale, and Global Assessment Question scores at baseline and at 3, 6, 9, and 12 months after treatment. Patients were considered responders whenever they showed improvement in erection parameters in all four assessments and responded positively to the Global Assessment Question. Adverse events were recorded. Statistical variables were applied and findings were considered statistically significant at a P value less than < .05. Results Eighty percent (mean age = 64.8 years) completed the 12-month follow-up. Positive response rates were 60% of available subjects at the end of the study and 48% of the intent-to-treat population. After the 12-month follow-up, 91.7% of responders maintained their responses. No patient reported treatment-related adverse events. Conclusion LISWT in patients with ED unresponsive to PDE5i treatment was effective and safe in 60% of patients treated. The efficacy response was maintained for 12 months in most patients.

Effectiveness of Tadalafil 5 mg Once Daily in the Treatment of Men with Lower Urinary Tract Symptoms Suggestive to Benign Prostatic Hyperplasia With or Without Erectile Dysfunction: Results from Naturalistic Observational TadaLutsEd Study

INTRODUCTION Naturalistic clinical trials provide data on the effectiveness of drugs in nonexperimental and everyday situations and are extremely helpful for decision-making purposes and for confirming experimental findings in clinical trials. No data have been published from naturalistic studies performed in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) with or without erectile dysfunction (ED) and treated with phosphodiesterase type 5 inhibitors. AIM The aim of this study (TadaLutsEd Study) was to assess, in the context of medical practice, the effectiveness of tadalafil 5 mg once daily in patients with LUTS/BPH with or without erectile dysfunction. METHODS The study was a 6-week uncontrolled, prospective, open-label, multicentric, observational study. The patient population involved sexually active males aged ≥ 50 years, diagnosed with LUTS/BPH with or without concomitant ED, and treated with tadalafil 5 mg daily in accordance with standard urological practice. MAIN OUTCOME MEASURES Effectiveness was assessed through the self-administered International Prostate Symptom Score (IPSS) questionnaire; quality of life was evaluated through the IPSS quality of life section (IPSS-QoL). The patients were also evaluated with the International Index of Erectile Function (IIEF-5). Adverse events were recorded. Statistical analyses using paired data samples was applied (Wilcoxon signed-ranks test). RESULTS Sixty-two patients (mean age 62.2 years) completed the treatment, of whom 85.5% showed improvement in their urinary symptoms. Pre- and post-treatment differences in the IPSS, IPSS-QoL, and IIEF-5 scores were statistically significant at 4.4, 1, and 5.4 points, respectively (P < 0.0001). Tadalafil was well tolerated, and adverse events were mild, with a discontinuation rate of 1.6%. CONCLUSION According to study results, the use of tadalafil 5 mg once daily in a nonselected patient population with LUTS/BPH with or without ED led to improvements in terms of symptoms and quality of life and exhibited a safety profile similar to that obtained in controlled tadalafil clinical trials.

ORIGINAL RESEARCHRisk Factors of Peyronie's Disease. What Does Our Clinical Experience Show?*

INTRODUCTION Peyronies disease (PD) is a localized fibrosis that affects the tunica albuginea of the penis. Its origin can be associated with coital penile trauma in men with autoimmune hypersensitivity and a presumed genetic predisposition. AIM To identify clinical and traumatic risk factors in a patient population with PD, when compared to a control group. METHODS From November 2007 to March 2010, 317 patients sought medical attention for PD. As control group, 147 consecutive patients, who came for a prostate exam, were studied. Clinical, traumatic, and sexual history of these patients was gathered. Risks factors were considered only if they had been present before the onset of PD symptoms. MAIN OUTCOME MEASURE The International Index of Erectile Function and the International Prostate Symptoms Score. A univariate logistic regression model (chi-square) (odds ratios [ORs] and 95% confidence intervals [CI]) was used to estimate the association of risk factors with PD; and the Students t-test was implemented for age. RESULTS The mean age of patients with PD and control group was 56.7 and 58.8, respectively (P<0.923). The mean evolution time of the disease was 17.7 months (2-48). Erectile dysfunction (ED) and coital trauma constituted the only two independent risk factors for PD compared to the control group (P<0.05 and 0.002, respectively) with an OR of 1.5 (95% CI 1.0-2.3) and 2.69 (95% CI 1.41-5.21), respectively. Patients with ED and diabetes mellitus and with a mild-to-moderate ED also presented a higher predisposition (P=0.008 and 0.00001), with an OR of 3.64 (95% CI 1.33-10.79) and 5.58 (95% CI 3.03-10.42), respectively. CONCLUSION Erectile dysfunction and coital trauma have proven to be independent risk factors for the development of PD.

Making the Diagnosis of Erectile Dysfunction

When we speak about diagnosing ED we refer to two major aspects of this diagnostic approach: diagnosis of the condition and diagnosis of the cause. Unfortunately, many physicians still consider ED a low priority during their patient’s medical evaluation; due to the ignorance of the relationship this condition has with different risk factors. This situation is worsened by possible patient misinformation and sometimes embarrassment to seek help for this symptom. From the epidemiologic point of view, ED is related to several major diseases: hypertension, cardiovascular disease, dyslipidemia, diabetes, and depression (Seftel et al. Journal d’Urologie 171, 2341–2345, 2004). This implies that ED is part of the presentation of those prevalent diseases, and the concept of asking about ED, especially in the higher risk populations, should be encouraged among physicians.