Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction

ABSTRACT Objective To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS) in patients with erectile dysfunction. Materials and Methods A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5), intravaginal ejaculatory latency time (IELT) and international prostate symptoms scores (IPSS). After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were measured. The independent-samples t-test was used to compare the pre- and post-treatment scores of the patients. Results The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL-1, 188.7±29.6mg/dL-1,104 (80-360) mg dL-1, respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01). Conclusion A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time.

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study

ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Efficacy of Tamsulosin, Oxybutynin, and their combination in the control of double-j stent-related lower urinary tract symptoms

ABSTRACT Introduction and objective Indwelling double J ureteral stents are used routinely in the resolution of ureteral obstruction caused by different etiologies. Evaluation of urinary symptoms related to double-J stent, indicate that these affect 73-90% of patients. We conducted a prospective, randomized study, to evaluate the efficacy of tamsulosin, oxybutinin and combination therapy in improving the urinary symptoms. Methods Patients who underwent ureteral stent placement after ureterolithotripsy (total 51), were randomized into three groups: Group I: Tamsulosin 0.4 mg. once per day(17 patients), Group II: Oxybutinin 5 mg. once per day (17 patients), Group III: Tamsulosin+ oxybutynin once per day (17 patients). All the groups received the drugs for three weeks and completed a Spanish validated Ureteral Stent Symptom Questionnaire (USSQ) at day 7 and 21. Results Repeated measures ANOVA showed mean urinary symptom index score was 22.3 vs. 15.5 in group three (p<0.001) at day 7 and 21 respectively. The mean work performance index was 6.6 vs 8.1 (p=0.049) favoring tamsulosin group, the mean sexual score was 0.5 vs 1.5 (p=0.03). Among additional problems the mean was 7.2 vs 6.2 (p=0.03). No significant difference was noted among pain and general health index. No side effects were reported. Conclusions Combination therapy with tamsulosin and oxybutynin improved irritative symptoms and work performance as well as sexual matters. Combination therapy should be considered for patients who complained of stent related symptoms.

[Impact of alfuzosin 10 mg once daily on quality of life in Tunisian patients, with lower urinary symptoms suggestive of benign prostatic hyperplasia]

Incidence of benign prostatic hyperplasia [BPH], one of the most common conditions affecting adult men, increases dramatically after the age of 50. The various symptoms of BPH, which include lower urinary tract symptoms [LUTS], can adversely affect quality of life [QoL] and sexuality and 1-Blockers are the most frequently prescribed oral medications as first-line treatment. The objectives of this study try to evaluate QoL and sexuality in patients requiring treatment by Alfuzosin 10mg once daily according to physician decision in current practice and to identify patient's profile treated with Alfuzosin 10 mg under daily practice conditions by Tunisian urologists. 730 patients presenting a symptomatic BPH were enrolled in this study by 40 urologists. The impact of treatment on patient's QoL and sexual dysfunction were checked at every visit before treatment and at 3 and 6 months using [International Prostate symptoms score] [IPSS] and [Male Sexual Health Questionnaire - Ejaculatory Dysfunction] [MSHQ - EJD] questionnaire. BPH affect Qol and near half of the patients reported sexual disorders. The treatment compliance to Alfuzosin was very good with a regular intake in 92% of the cases. Quality of life significantly improves during visits: the global IPSS score decreases from 18.8 at baseline to 9.5 at 6 months. The same favorable evolution was observed with the bother score which decreases from 4.0 at baseline to 1.6 at 6 months, and with MSHQ - EJD score which increases from 10.5 at first visit to 11.4 at 6 months. Alfuzosin 10 mg administered for 6 months provides a marked improvement in patients presenting symptomatic BPH not only on LUTS but also in QoL and sexual disorders

Effect of weight reduction on the severity of lower urinary tract symptoms in obese male patients with benign prostatic hyperplasia: A randomized controlled trial

PURPOSE: We assessed whether weight reduction is an effective intervention for the management of lower urinary tract symptoms (LUTS) and investigated the relationship between obesity and LUTS. MATERIALS AND METHODS: This was a prospective randomized controlled trial that enrolled obese men older than 50 years with LUTS. The study period was 52 weeks. All patients received standardized alpha-adrenergic blocker therapy for the treatment of benign prostatic hyperplasia (BPH) during the run-in period. Patients were randomized to receive either a standardized prerecorded video program on the general principle of weight reduction or a comprehensive weight reduction program. Patients were assessed at different time points with symptom assessment, uroflowmetry, transrectal ultrasound, and metabolic assessment. RESULTS: Sixty-five patients were allocated to each study arm. After the study period, no significant difference in weight reduction was found between the two arms. When the pre- and postintervention parameters were compared, none were statistically different between the 2 arms, namely nocturia, International Prostate Symptom Score, quality of life assessment, and uroflowmetry parameters. When the whole study population was taken as a single cohort, these parameters were also not significantly different between the group with a body mass index of 25 to <30 kg/m2 and the group with a BMI of 30 to 35 kg/m2. CONCLUSIONS: We found no association between obesity and LUTS. This could have been due to the less marked weight difference in our cohort. Whereas weight reduction may be an effective measure to improve LUTS, the implementation of a successful program remains a challenge.

Effects of prostatic inflammation on LUTS and alpha blocker treatment outcomes

Purpose To evaluate the association between prostatic inflammation and lower urinary tract symptoms (LUTS), and to identify the effects of prostatic inflammation on the treatment with an alpha blocker. Materials and Methods 111 Participants who were aged ≥ 50 years, the presence of LUTS (maximal flow rate < 20 m/s, IPSS ≥ 11), and an elevated PSA level (3-20ng/mL) were treated with tamsulosin 0.2mg once daily for 3 months after prostate biopsies. Prostatic inflammation was scored as none (0), mild (I), moderate (II), or marked (III). LUTS parameters including urine flow rates, IPSS, PSA, and prostate volume were evaluated. Results Inflammation grading resulted in 25, 60, and 26 patients that were grade 0, I, and II, respectively. Lower grade inflammation was related to higher urine flow rate at baseline. Patients with higher inflammation grades had larger prostate volumes, larger total and transitional zone volumes, and higher PSA levels. Overall, urine flow rates and residual urine volume were improved after 3 months of alpha blocker therapy. Eighty percent of patients with grade 0 inflammation, 73% of patients with grade I inflammation, and 92.3% of patients with grade II inflammation showed improvement of LUTS after treatment. Longer duration of treatment was related to a decreased chance of improvement of LUTS. Patients with increased IPSS voiding subscales could be predictive of improvement of LUTS. Conclusions Patients with high grade inflammation had lower flow rates and higher prostatic volumes than patients with low grade inflammation. Inflammation grade did not affect the outcomes of alpha blocker treatment. .

Neurological status predicts response to alpha-blockers in men with voiding dysfunction and Parkinson's disease

OBJECTIVES: To evaluate predictors of the response to doxazosin, a selective alpha-adrenoceptor antagonist, when used for the treatment of lower urinary tract symptoms in men with Parkinson's disease. METHODS: In a prospective study, 33 consecutive men (mean age 59.2±7.0 years) with Parkinson's disease and lower urinary tract symptoms were evaluated. Neurological dysfunction was assessed with the Unified Parkinson's Disease Rating Scale. Urological assessment was performed at baseline and after 12 weeks of treatment with 4 mg/day of extended-release doxazosin, including symptom evaluation with the International Continence Society male short-form questionnaire, an assessment of the impact of lower urinary tract symptoms on quality of life and urodynamics. Clinical and urodynamic predictors of response were specifically evaluated. RESULTS: Compared with the score at baseline, the total International Continence Society male short-form score was reduced after doxazosin administration, from 17.4±7.5 to 11.1±6.9 (p<0.001). The impact of lower urinary tract symptoms on quality of life was also significantly reduced, from 1.8±1.1 to 1.0±1.0 (p<0.001) and the maximum urinary flow varied from 9.3±4.4 to 11.2±4.6 ml/s (p = 0.025). The severity of neurological impairment ...

Efficacy and safety of propiverine and terazosine combination for one year in male patients with luts and detrusor overactivity

Purpose To evaluate the long term efficacy and safety of the use of propiverine and terazosine combination in patients with LUTS and DO by a placebo controlled study. Materials and Methods One hundred patients were enrolled in the study. They were randomized into two groups (each group consisted of 50 patients). Terazosine and placebo were administered to the patients in Group 1 and terazosine plus propiverine HCL was administered to Group 2. The patients were evaluated by international prostate symptom score (IPSS), the first four questions of IPSS (IPSS4), the 8th question of IPSS (quality of life-QoL), overactive bladder symptom score questionnaire (OAB-q V8), PSA test, urodynamic studies, post voiding residue (PVR). All patients were followed for one year and were reassessed for comparison. Results IPSS, IPSS4, OAB symptoms, QoL score, PVR, and Qmax scores of the groups did not differ. After one year treatment, there was significant improvement in IPSS, IPSS4, OAB symptoms, QoL and Qmax values in Group 2. No significant improvement was noted for the same parameters in Group 1. Conclusion This is the first study to show long term safety and efficacy of anticholinergic therapy for patients with LUTS. In patients with OAB or DO, long term anticholinergic treatment may be regarded as a treatment option. .

Evaluation of Tadalafil effect on lower urinary tract symptoms of benign prostatic hyperplasia in patients treated with standard medication

OBJECTIVES: To evaluate safety and efficacy of tadalafil on lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in patients treated with standard medication. MATERIALS AND METHODS: In this case-controlled randomized clinical trial, from November 2008 to August 2009, 132 patients with obstructive and irritative urinary tract symptoms due to BPH, IPSS > 8, no indication for surgical intervention and that reached plateau levels of response to treatment were selected. These patients were randomly allocated in two groups (each containing 66 patients). The treatment group received standard treatment of BPH and tadalafil (10 mg nightly); the placebo group received only standard treatment of BPH. IPSS, maximum urinary flow rate (Qmax) and quality of life were assessed before and after a 3-month period of study. RESULTS: Before treatment, mean IPSS, Qmax and quality of life values in the treatment and placebo groups were 13.06 ± 4.37 and 13.66 ± 4.25, 8.92 ± 2.96 mL/s and 9.09 ± 2.91 mL/s, 2.93 ± 0.86 and 2.66 ± 0.78, respectively. After treatment, mean IPSS, Qmax, and quality of life values in treatment group were 7.66 ± 3.99, 9.99 ± 4.76 mL/s and 1.80 ± 0.98, respectively. These findings were compared to corresponding values of the placebo group (11.37 ± 3.64, 8.73 ± 2.22 mL/s and 2.19 ± 0.53, respectively): IPSS and quality of life were significantly different but Qmax didn't show a significant change. CONCLUSIONS: Tadalafil improves quality of life and urinary symptoms in patients with LUTS suggestive of BPH, but doesn't have any significant effect on Qmax. Therefore, this drug may be effectively used in combination with standard medical therapies for BPH.

The efficacy and safety of oral Tamsulosin controlled absorption system (OCAS) for the treatment of lower urinary tract symptoms due to bladder outlet obstruction associated with benign prostatic hyperplasia: an open-label preliminary study

AIMS: Tamsulosin, a superselective subtype alpha 1a and 1d blocker, is used for the treatment of male lower urinary tract symptoms (LUTS) commonly caused by benign prostatic hyperplasia (BPH). This prospective study evaluated the efficacy and safety of a new formulation, Tamsulosin OCAS® (Oral Controlled Absorption System), for LUTS associated with BPH in Thai patients. MATERIALS AND METHODS: Fifty one patients over 40 years old with complaints of LUTS associated with BPH were recruited. Patients received an 8 week course of once daily 0.4 mg tamsulosin OCAS®, and were followed up at 2 (visit 3), 4 (visit 4) and 8 (visit 5) weeks post-treatment. At each visit, patients were assessed using the International Prostate Symptom Score (IPSS), Nocturia Quality of Life (N-QoL) Questionnaire, QoL Assessment Index (IPSS-QoL), and International Index of Erectile Function (IIEF). The primary outcome was efficacy of Tamsulosin. The secondary outcomes included change in the mean number of nocturia episodes, hours of undisturbed sleep (HUS) and uroflowmetry measurements. RESULTS: Total IPSS significantly decreased at week 8 from baseline (from 19.52 to 6.08; p < 0.001). Similarly, the voiding and storage subscores of IPSS also continued to improve significantly starting from the second and third visits, respectively (p < 0.001 versus baseline). The IPSS-QoL and N-QoL scores significantly improved at visit 3 through end of study. In addition, we observed significant nocturia and HUS improvement in their last clinic visit. Uroflowmetry parameters, Qmax and Qave, improved significantly at 3rd clinic visit . Three patients experienced mild dizziness. CONCLUSION: Tamsulosin OCAS® treatment led to significant improvements in LUTS, HUS and QoL in Thai patients with bladder outlet obstruction from BPH with few side effects.