Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial.

BACKGROUND: The KEYNOTE-057 trial evaluated activity and safety of pembrolizumab in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer who were ineligible for or declined radical cystectomy. In cohort A (patients with carcinoma in situ, with or without papillary tumours) of the KEYNOTE-057 study, pembrolizumab monotherapy led to a complete response rate of 41% at 3 months, and 46% of responders maintained a response lasting at least 12 months. Here, we evaluate pembrolizumab monotherapy in cohort B of patients with papillary tumours without carcinoma in situ. METHODS: KEYNOTE-057 is a single-arm, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. Cohort B eligible patients were aged 18 years and older, had an Eastern Cooperative Oncology Group performance status of 0-2, and had BCG-unresponsive high-risk non-muscle-invasive bladder cancer with papillary tumours (high-grade Ta or any-grade T1) without carcinoma in situ. Transurethral resection of bladder tumour within 12 weeks of first pembrolizumab dose was required. Patients received pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles. Primary endpoint was 12-month disease-free survival of high-risk non-muscle-invasive bladder cancer or progressive disease as assessed by cystoscopy, cytology, and central pathology and radiology review. Activity was assessed in all patients who received at least one dose of the study drug and had a baseline evaluation. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961, and is ongoing. FINDINGS: Between April 12, 2016, and June 17, 2021, 132 patients (104 [79%] men and 28 [21%] women) who had received a median of ten (IQR 9-15) previous BCG instillations were enrolled into cohort B of the study. Patients received a median of 10 cycles (IQR 6-27) of pembrolizumab. At data cutoff date, Oct 20, 2022, median follow-up was 45·4 months (IQR 36·4-59·3) and five (4%) of 132 patients remained on treatment. The 12-month disease-free survival was 43·5% (95% CI 34·9-51·9). Treatment-related adverse events occurred in 97 (73%) of 132 patients; 19 (14%) had a grade 3 or 4 treatment-related adverse event; the most common grade 3 or 4 treatment-related adverse events were colitis (in three [2%] patients) and diarrhoea (in two [2%]). 17 (13%) of 132 patients experienced serious treatment-related adverse events, of which colitis (three patients [2%]) was most common. No treatment-related deaths occurred. INTERPRETATION: Pembrolizumab monotherapy showed antitumour activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer without carcinoma in situ and could potentially be a suitable treatment option for patients who decline or are ineligible for radical cystectomy. Findings will need to be confirmed in a randomised controlled trial. FUNDING: Merck Sharp & Dohme.

The impact of hyperthyroidism on sexual functions in men and women: a systematic review and meta-analysis.

This study aimed to review the current knowledge on sexual dysfunction in men and women with hyperthyroidism through a systematic review and meta-analysis. Available clinical trials from the MEDLINE database were searched using a prerecorded protocol (Protocol Prospero ID: CRD42022340587), and obtained data were analyzed and reported according to the PRISMA guidelines. Pooled effect estimates were computed using a random-effects model. Twenty eligible studies were identified, of which 15 were included in this meta-analysis. The prevalence of erectile dysfunction was significantly higher in participants with hyperthyroidism than that in controls [odds ratio = 9.16 (95% confidence interval [CI], 5.0-16.5)]. Treatment of hyperthyroidism alone improved erectile functions [effect size, ES = 0.36 (95% CI, -0.01-72)] and mean intra-vaginal ejaculation latency time [ES = 0.63 (95% CI, 0.27-98)] among men with erectile dysfunction and/or premature ejaculation. The prevalence of premature ejaculation also decreased with treatment of hyperthyroidism [odds ratio = 0.11 (95% CI, 0.04-28). Women with hyperthyroidism demonstrated higher odds in female sexual dysfunction than controls [odds ratio = 4.34 (95% CI, 2.63-7.18)]. Female sexual function index scores in women with hyperthyroidism were also significantly lower than those in the controls with moderate effect sizes. An evident and reversible disruption of sexual functions under hyperthyroidism conditions was observed in both sexes.

Bilateral orchiectomy deteriorates the structure and function of seminal vesicles in a rat model.

The effects of hormone levels on ejaculation are known. In addition to thyroid hormone levels, testosterone levels are also associated with ejaculation, but no consensus has been reached on this issue. Thus, we investigated the effect of decreased testosterone levels due to bilateral orchiectomy on the chemical stimulation-induced ejaculation phases in rats. Twenty-one male Wistar rats were randomized into the orchiectomy, sham, and control groups, with seven rats in each group. Bilateral orchiectomy was performed. The ejaculation parameters were evaluated 5 days after the sham and bilateral orchiectomy operations and the waiting period in the control group. The seminal vesicle (SV) phasic contraction number and increase in basal pressure amplitude were significantly lower in the orchiectomy group (6.9 ± 3.3 and 0.6 ± 0.3 mmHg) than in the sham and control groups (11.2 ± 1.7 and 1.0 ± 0.4 mmHg, and 14.5 ± 6.6 and 1.1 ± 0.2 mmHg, respectively; p = 0.016 and p = 0.03, respectively). The interval between the SV contractions was significantly longer in the orchiectomy group (166.2 ± 104.3 s) than in the sham and control groups (76.0 ± 15.5 s and 63.1 ± 31.1 s, respectively; p = 0.014 (between groups), orchiectomy vs sham p = 0.040 and orchiectomy vs control p = 0.018). The SV weights of the rats were significantly lower in the orchiectomy group (0.14 ± 0.01 g) than in the sham and control groups (0.37 ± 0.05 g and 0.48 ± 0.03 g respectively; p < 0.0001 (between groups), orchiectomy vs sham p < 0.0001 and orchiectomy vs control p < 0.0001). The groups showed no significant differences in ejaculation time, SV basal pressure, SV maximum amplitude, and bulbospongiosus muscle contraction electromyographic activity. Our results partially clarified the relationship between decreased testosterone levels and ejaculation. Decreased testosterone levels caused statistically significant changes in SV functions and affected the ejaculation emission phase.

Systematic review and meta-analysis for the value of thyroid disorder screening in men with ejaculatory dysfunction.

OBJECTIVE: To demonstrate evidence from available clinical studies to clarify the scientific points that have been achieved in relation to thyroid disorders and ejaculatory dysfunction (EjD). DATA SOURCES: Clinical trial articles published in English on Medline. ELIGIBILITY CRITERIA: Clinical studies that investigated the association of thyroid disorders with the ejaculatory function of subjects and the trials evaluating the effect of thyroid dysfunction treatment on the ejaculatory function of the subjects were eligible. SYNTHESIS METHODS: We searched Medline with "ejaculation" and different combinations of "thyroid," "serum TSH," "serum T3," "serum T4" keywords in PubMed. RESULTS: Standardised mean serum thyroid-stimulating hormone (TSH) levels in premature ejaculation (PE) sufferers differed from non-PE control subjects (P = .05). Hyperthyroidism was associated with increased odds among PE subjects (OR = 2.0, P = .03). Delayed ejaculation was seen with increased odds in hypothyroid patients compared with hyperthyroidism patients (OR = 57, P = .0001). Serum TSH and mean intra-vaginal ejaculation latency time (IELT) of the subjects showed a correlation both before and after treatment for thyroid disorder. Treatment of thyroid disorders improved the mean IELT measures of the subjects. The overall estimate of the effect of hyperthyroidism treatment on mean IELT was .64 (P = .0001) in the random-effects model. LIMITATIONS: The low quality and quantity of evidence from available studies limited the interpretation of our study findings. CONCLUSIONS: The causal relationship between EjD and thyroid disorders remains to be clarified. Sufferers of delayed ejaculation acquired PE subjects, and PE sufferers who have accompanying erectile dysfunction and/or anxiety may benefit from thyroid disorder investigation.

Urinary microbiota; Which non-invasive urine collection method should we use?

OBJECTIVE: The aim of this study is to establish the optimal non-invasive urine sample collection method for the microbiota studies. METHODOLOGY: Twelve men with bladder carcinoma underwent first voided and midstream urine collection. Urine samples were analysed using V3-V4 regions of bacterial 16s ribosomal RNAs. Bacterial groups with relative abundance above 1% were analysed in first voided urine and midstream urine samples at phylum, class, order and family level. At the genus level, all of the identified bacterial groups' relative abundances were analysed. The statistical significance (P < .05) of differences between first voided and midstream urine sample microbiota was evaluated using the Wilcoxon test. RESULTS: According to the analysis, 8 phyla, 14 class, 23 orders, 39 families and 29 different genera were identified in the first voided and the midstream urine samples. Statistical differences were not identified between first voided and midstream urine samples of all bacteria groups except the Clostridiales at order level (p:0.04) and Clostridia at class level (P: .04). CONCLUSIONS: Either first voided or midstream urine samples can be used in urinary microbiota studies as we determined that there is no statistically significant difference between them regarding the results of 16s ribosomal RNA analysis.

Easily accessible, up-to-date and standardised training model in Urology: E-Learning Residency training programme (ERTP).

OBJECTIVES: There is no standardised and up-to-date education model for urology residents in our country. We aimed to describe our National E-learning education model for urology residents. METHODOLOGY: The ERTP working group; consisting of urologists was established by the Society of Urological Surgery to create E-learning model and curriculum in April 2018. Learning objectives were set up in order to determine and standardise the contents of the presentations. In accordance with the Bloom Taxonomy, 834 learning objectives were created for a total of 90 lectures (18 lectures for each PGY year). Totally 90 videos were shot by specialised instructors and webcasts were prepared. Webcasts were posted at uropedia.com.tr, which is the web library of the Society of Urological Surgery. The satisfaction of residents and instructors was evaluated with feedbacks. An assessment of knowledge was measured with the multiple-choice exam. RESULTS: A total of 43 centres and 250 urology residents were included in ERTP during the academic year 2018/2019. There were 93/55/43/34/25 urology residents at 1st/2nd/3rd/4th and 5th year of residency, respectively. Majority of the residents (99.1%) completed the ERTP. The overall satisfaction rate of residents and instructors were 4.29 and 4.67 (min: 1 so bad, max: 5 so good). An assessment exam was performed to urology residents at the end of the ERTP and the mean score was calculated as 57.99 points (min: 20, max: 82). CONCLUSION: As a result of the COVID-19 pandemic, most of the educational programmes had to move online platforms. We used this reliable and easily accessible e-learning platform for the standardisation of training in urology on national basis. We aim to share this model with international residency training programmes.

Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats.

INTRODUCTION: Although premature ejaculation (PE) is the most common sexual dysfunction in young men, its true pathophysiology has not yet been clearly elucidated. AIM: To investigate the quantitative changes that occurred in an ejaculation model induced by para-chloroamphetamine (PCA) after botulinum-A toxin injection into the bulbospongiosus (BS) muscle in rats. METHODS: A total of 21 male rats weighing 300 to 350 grams were used in the study. The animals were divided into 3 groups: control, 1 unit of botulinum-A toxin injected, and 5 units of botulinum-A toxin injected. The botulinum-A toxin was percutaneously injected into the BS muscle, and the experiment was carried out 96 hours (5 days) after the injection. MAIN OUTCOME MEASURE: The seminal vesicle (SV) was cannulated, and the BS muscle was dissected and connected to an amplifier (Biopac; Goleta, CA) to record the pressure and electromyography measurement. The ejaculation parameters were obtained after the PCA injection. RESULTS: The ejaculation latency time of the group receiving 5 units of botulinum-A toxin was statistically significantly longer (1092 ± 657 seconds) compared to the control group (298 ± 81 seconds) and the group receiving 1 unit of botulinum-A toxin (439 ± 100 seconds) (P = .003). Furthermore, the BS EMG area under the curve values for the group receiving 5 units of botulinum-A toxin were significantly lower (7.4 ± 1.2 V/s × 10-4) than those of the control group (13.6 ± 4.0 V/s × 10-4) and the group receiving 1 unit of botulinum-A toxin (13.6 ± 5.0 V/s × 10-4) (P = .009). No statistically significant difference was found between the groups in terms of the basal SV pressure, number of SV phasic contractions, maximum amplitude of the SV phasic contraction, and intervals between the SV phasic contractions and the BS muscle contractions. CLINICAL IMPLICATIONS: Botulinum-A toxin injection is a potential treatment option for PE and should be further investigated by future clinical studies. STRENGTHS AND LIMITATIONS: Ease of administration and prolonged duration of botulinum-A toxin are advantages of the existing treatment options. The risk of anejaculation due to the dosage should be kept in mind. CONCLUSIONS: Injection of botulinum-A toxin into the BS muscle in rats significantly delayed the ejaculation latency time and affected the expulsion phase. Ongün S, Acar S, Koca P, et al. Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats. J Sex Med 2019;16:1338-1343.

Clinical Behavior of Bladder Urothelial Carcinoma in Young Patients: A Single Center Experience.

Background. There is not enough evidence about clinical behavior of bladder cancer in younger patients. Objective. We aimed to evaluate the clinical characteristics and prognosis of bladder urothelial carcinoma patients under the age of 40 years. Methods. Medical records of patients listed in our cancer database were retrospectively reviewed. A total of 40 patients who were initially diagnosed with bladder urothelial carcinoma at the age less than 40 years were included in the study. Patients' records were reviewed for recurrence and progression rates, demographic data, medical history, and treatment modalities. Results. Pathological results revealed 33 (82.5%) Ta low-grade, 6 (15%) T1 high-grade, and 1 (2.5%) T2 high-grade urothelial carcinomas. Recurrence was detected in 14/39 (35.9%) patients but progression was not observed in any patients. The mean age of recurrent patients was significantly higher than nonrecurrent patients (34.8 versus 28.5 years; p < 0.05). Besides, recurrence was detected in only 1 patient with the age under 30 years (6.2%) and 13 patients (54.1%) between 30 and 40 years old, respectively (p < 0.05). Conclusion. Bladder urothelial carcinoma diagnosed at young age tends to be a low pathologic stage, with relatively low rate of recurrence and progression.

Effects of resveratrol on the alterations of cavernosal eNOS and LOX-1 expression in the hypercholesterolemic condition: a preliminary study.

BACKGROUND/AIM: The aim of this study was to determine the effects of resveratrol on the alterations of cavernosal eNOS and LOX-1 mRNA expression in the hypercholesterolemic condition. MATERIALS AND METHODS: Twenty-one New Zealand white male rabbits were separated into three groups. Rabbits were fed with a normal dietary intake for the control group and a 2% cholesterol diet for the hypercholesterolemia and resveratrol groups for 6 weeks. Resveratrol 4 mg/kg daily was administered for the resveratrol group. Cavernosal LOX-1 and eNOS mRNA expressions were determined with real-time RT-PCR in all groups. The statistical analysis was performed with the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: We found no difference between mean LOX-1 mRNA expression levels in the three groups. Lower mean eNOS mRNA expression level was determined in the hypercholesterolemia group when compared with the control group (P = 0.011). Mean eNOS mRNA expression level in the resveratrol group was similar to that in the control group but significantly higher than that in the hypercholesterolemia group (P < 0.001). CONCLUSION: This preliminary study demonstrates the beneficial effects of resveratrol on cavernosal eNOS expression. The presence of cavernosal LOX-1 expression was also shown for the first time. Resveratrol may be an alternative option in hypercholesterolemic erectile dysfunction with further studies supporting its beneficial effects on the corpus cavernosum.

Resveratrol Protects and Restores Endothelium-Dependent Relaxation in Hypercholesterolemic Rabbit Corpus Cavernosum.

INTRODUCTION: Oxidative stress dependent-decrease in nitric oxide (NO) bioavailability plays an integral role in hypercholesterolemia-induced erectile dysfunction (ED). Resveratrol has been demonstrated to exert beneficial effects against oxidative stress and improve NO bioavailability. AIM: The protective and restorative potentials of resveratrol on endothelium-dependent relaxations were evaluated in hypercholesterolemic rabbit corpus cavernosum (CC). METHODS: Hypercholesterolemia was induced by administering 2% cholesterol diet (CD) (w/w) to the rabbits for 6 weeks. Two different protocols were applied to test the effects of resveratrol on hypercholesterolemia-induced ED. In Protocol-1 (P1), resveratrol was administrated to the rabbits simultaneously with CD in order to evaluate the protective effect, and for Protocol-2 (P2), resveratrol was administrated for 6 weeks after termination of CD in order to evaluate the restorative effect. MAIN OUTCOME MEASURES: Endothelium-dependent relaxations of CC were evaluated by using organ bath studies. In order to elucidate the possible molecular mechanisms, we measured endothelial NO synthase (eNOS) and phosphovasodilator-stimulated phosphoprotein (VASP) expressions and activations, NADPH oxidase, superoxide dismutase (SOD), and catalase (CAT) and glutathione peroxidase (GPx) activity in cavernosal tissues obtained at the end of the study. RESULTS: Resveratrol showed an improvement in the endothelium-dependent relaxation responses in vitro. We demonstrated significantly increased activatory-phosphorylation (p[S1177]-eNOS) and activated phosphovasodilator-stimulated phosphoprotein (phospho-VASP) levels, but reduced phosphorylation (p[T495]-eNOS) of eNOS and NADPH oxidase activity in the resveratrol-administered HC animals compared with hypercholesterolemic control rabbits in the P1. In the P2, resveratrol exhibited an improvement in endothelium-dependent relaxation responses and more pronounced effects on eNOS activation. CONCLUSION: Resveratrol administration, either simultaneously with HC diet or after HC, caused an improvement in the endothelium-dependent relaxation responses in the CC, suggesting its potential in both protective and restorative purposes in hypercholesterolemic rabbit CC.

Investigation of the neural target level of hyperthyroidism in premature ejaculation in a rat model of pharmacologically induced ejaculation.

INTRODUCTION: Association between hyperthyroidism and premature ejaculation was demonstrated in clinical studies. AIM: The aim of this study is to determine the target level of changes on ejaculatory physiology under hyperthyroid states. METHODS: p-Chloroamphetamine (PCA)-induced pharmacologic ejaculation model with 24 male Wistar rats was used in the study. Subcutaneous injection of L-thyroxine for 14 days was performed to induce hyperthyroidism. At the end of the injection period, thyroid hormone status was evaluated by serum thyroid-stimulating hormone measurements in all rats. At the beginning of the operations, complete spinal transections (tx) at the T8-T9 level were performed to half of the L-thyroxine-injected and control group rats. Thus, experimental groups were constructed as follows: Group 1--control-spinal intact (n=6), group 2-control-spinal tx (n=6), group 3-hyperthyroid-spinal intact (n=6), and group 4-hyperthyroid-spinal tx (n=6). Ejaculatory responses were recorded before and 30 minutes after intraperitoneal administration of 5 mg/kg PCA. MAIN OUTCOME MEASURES: During the operations, seminal vesicle (SV) catheterization and bulbospongiosus (BS) muscle dissections were performed in all rats to demonstrate SV pressure (SVP) BS electromyographic (EMG) activity changes. RESULTS: Following PCA administration SVP tonic amplitude, SV phasic contraction (SVPC) frequency, SVPC maximal amplitude, and BS EMG area under curve values were higher in hyperthyroid intact rats than in control intact rats. The time interval between PCA administration and first ejaculation of hyperthyroid intact rats were significantly shorter than control intact rats (261 ± 7.30 seconds vs. 426 ± 49.6 seconds, P=0.008). All of the changes in the ejaculatory parameters that were induced by hyperthyroidism were completely resolved after spinal transections at the T8-T9 level in group 4. CONCLUSION: In this study, we confirmed the recent data that hyperthyroidism affects both the emission and expulsion phases of ejaculation. The changes that were induced by hyperthyroidism on ejaculatory physiology probably take place in the supraspinal centers above T8 level.

Acute effects of hypercholesterolemic diet on erectile responses in rats.

OBJECTIVE: The aim of this study was to evaluate the acute effects of a high cholesterol diet (HCD) on erectile and endothelial functions in Sprague-Dawley rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 2 groups as control and HCD groups. The control group was fed on a normal diet and the hypercholesterolemia group was fed a 1% cholesterol-enriched diet daily for 2 weeks. Total cholesterol levels were measured at the end of 2 weeks in both groups. To examine the effect of HCD on erectile function, electric cavernous nerve stimulation (CNS) at 20 Hz with a pulse duration of 1 ms for 1 min at 5 V was performed. During CNS, we measured intracavernous pressure (ICP), mean arterial pressure (MAP), detumescence time and area under the curve (AUC). To evaluate the endothelial responses, acetylcholine (Ach) was applied cumulatively (1 nM to 1 microM) to thoracic aorta tissues contracted with 60 mM KCl. RESULTS: In the HCD group total cholesterol levels were significantly higher than in the control group (148.1 +/- 18.9 vs. 55.7 +/- 8.1 mg/dl, p = 0.002). The detumescence time was significantly decreased after HCD compared to the control diet (19.3 +/- 3.6 vs. 78.6 +/- 12.8 s, p < 0.001). The decreases in the HCD group were also significant in terms of ICP (53.4 +/- 4.5 vs. 35.6 +/- 5.5 mm Hg; p < 0.05), ICP/MAP (55.9 +/- 3.9 vs. 38.2 +/- 5.2%; p < 0.05) and AUC (1,404 +/- 197.1 vs. 2,250 +/- 253.7, p < 0.05) values. There were no significant changes in maximum relaxation responses of the thoracic aorta to Ach. CONCLUSION: These results suggest that erectile functions were significantly damaged early in HCD rats. However, endothelial functions, evaluated in the thoracic aorta, were not affected simultaneously with erectile functions in rats fed a low concentration of HCD.

The effect of alpha-blocker therapy on erectile functions in patients with lower urinary tract symptoms due to benign prostate hyperplasia.

In this study we aimed to evaluate the impact of doxazosin treatment on erectile functions in patients with lower urinary tract symptoms (LUTS) and having erectile dysfunction (ED) at baseline. Fifty-three patients with LUTS (IPSS score > 7) whose maximum flow rate (Q(max)) < 15 mL s(-1) and PSA < 4 ng dL(-1) were enrolled in the study. Patients received doxazosin 4 mg once daily for 6 weeks. Subjective efficacy was assessed by IPSS, IPSS-Quality of Life (IPSS-QoL) for LUTS and efficacy was assessed by International Index of Erectile Function (IIEF) for erectile functions at baseline and sixth weeks. The objective efficacy was assessed by Q(max). The patients were classified according to their self reported erectile status: group I had ED and group II did not have ED. At the endpoint, doxazosin significantly improved the total IPSS score (-7.7 +/- 6.1, P = 0.006), IPSS-QoL score (-1.5 +/- 1.5, P = 0.024) and Q(max) (3.2 +/- 4.6 mL s(-1), P = 0.002) over baseline. Mean decrease in IPSS and IPSS-QoL scores after the treatment period were 6.9 +/- 6.4 (P < 0.001) and 0.95 +/- 1.80 (P < 0.05) in group I, whereas 8.2 +/- 5.8 (P < 0.001) and 1.9 +/- 1.1 in group II (P < 0.001), respectively. Mean changes of Q(max) values were 2.3 +/- 3.3 mL s(-1) in group I (P < 0.05) and 3.7 +/- 5.3 mL s(-1) in group II (P < 0.001). The improvement of IIEF-EF scores after the treatment period was only significant for group I. The efficacy of alpha-blocker therapy for LUTS was better by means of symptomatic relief for patients who did not have ED when compared with patients who had ED at baseline. However, slight improvement in erectile functions with alpha-blocker therapy was only seen in LUTS patients with ED.

Factors associated with phosphodiesterase type 5 inhibitor treatment satisfactions: results of patient interrogation.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitor therapy is an efficacious means of treatment for erectile dysfunction (ED). PDE5 inhibitors supply penile erection by inhibiting the hydrolysis of cGMP and therefore relaxing the corpus cavernosum. In this study, retrospective evaluation of those patients who were admitted to our clinic with the complaint of ED and who were recommended on PDE5 inhibitor treatment in terms of follow-up results and patient satisfaction were aimed. METHOD: The patients were called by phone and after informing about the study and taking the informed consent, patient satisfaction with the treatment, purposes of withdrawal, treatment alterations and partner satisfaction were investigated. RESULTS: Interviews were made with 345 patients, who accepted to enroll in the study and the mean patient age was 56 +/- 11.2 years. Of the patients 66.4% were learned to be satisfied with the treatment. It was determined that 10.7% of the patients have never used the medication and 50% could not continue because of high drug cost. It was recognised that 50.2% of the patients who are not satisfied with the treatment tried another PDE5 inhibitor. The success rate of the treatment was found to be higher in the followed-up group than those losses to follow-up. CONCLUSION: Therapy with PDE5 inhibitors is an effective means of ED treatment. The importance of doctor-patient communication should be considered, and the patient should be advised for adaptation to follow-up program. High drug cost is a significant predictor of patient compliance to treatment continuation.

Penile vascular impairment in erectile dysfunction patients with metabolic syndrome: penile Doppler ultrasound findings.

BACKGROUND: The constellation of truncal obesity, glucose intolerance, dyslipidemia (high triglycerides, low HDL cholesterol), and hypertension has been recognized as metabolic syndrome. However, the pathophysiological association between metabolic syndrome and erectile dysfunction (ED) has not yet been clearly determined. This study aimed to evaluate the penile Doppler ultrasound (PDU) findings of ED patients with metabolic syndrome. PATIENTS AND METHODS: Sixty-one age-matched ED patients with or without metabolic syndrome were included in the study. Patients were investigated by grouping according to risk factors of metabolic syndrome with PDU parameters (5th, 10th and 20th minute peak systolic velocity and end-diastolic velocity). PDU parameters of patients with and without metabolic syndrome were compared. RESULTS: The mean age of the patients were 54.9 +/- 8.3 and 54.9 +/- 7.6 years for the groups of with (n = 27) and without (n = 34) metabolic syndrome, respectively. When the mean peak flow velocities were compared with presence of metabolic syndrome, we observed differences between at the 5th, 10th and 20th minute peak systolic velocities (p = 0.083, p = 0.022 and p = 0.080, respectively). CONCLUSION: Metabolic syndrome seems to be the potential risk factor for ED, which may exert its effect by decreased arterial inflow due to endothelial dysfunction.

An experimental approach to the interrelationship between hyperthyroidism and ejaculation latency time in male rats.

PURPOSE: We investigated the effects of experimentally induced hyperthyroidism on seminal vesicle pressure measurements and bulbospongiosus muscle contractile activity in a para-chloroamphetamine (Sigma-Aldrich) induced ejaculation model in rats. MATERIALS AND METHODS: Male Wistar rats were used in the study. Daily injection of 25 microg/100 gm body weight L-thyroxine (T4, Sigma-Aldrich) for 14 days was performed in 14 rats to induce hyperthyroidism. Seven L-thyroxine injected rats were in the hyperthyroid group. The remaining 7 rats (recovery group) underwent operation after a 28-day washout period to determine spontaneous recovery from hyperthyroidism. At each operation seminal vesicle catheterization was done to measure intraluminal pressure and bulbospongiosus muscle dissection was performed for electromyography. After intraperitoneal administration of 5 mg/kg para-chloroamphetamine physiological parameters related to the ejaculatory process were measured. RESULTS: The interval between para-chloroamphetamine administration and first ejaculation was significantly decreased in the hyperthyroid rat group compared with that in the control group (mean +/- SD 202.8 +/- 22.3 vs 465.4 +/- 104.6 seconds, p = 0.001). Seminal vesicle phasic contraction frequency was significantly higher than control group values in hyperthyroid rats (for 30 minutes 32.3 +/- 13.9, p = 0.047). The mean AUC of bulbospongiosus muscle electromyography activity was also significantly increased in this group (11.1 +/- 4.1 V per second x 10(-4), p = 0.0001). All parameters in recovery and control group rats were not significantly differed from each other. CONCLUSIONS: Hyperthyroidism leads to enhanced seminal vesicle contraction frequency and bulbospongiosus muscle contractile activity in rats. Hyperthyroidism affects the emission and expulsion phases of ejaculation in reversible fashion.

Sexual function status in women with obstructive sleep apnea syndrome.

INTRODUCTION: Several co-morbid diseases have been shown to affect sexual functions in both genders. In the literature, sexual function status in men with obstructive sleep apnea syndrome (OSAS) has been studied; however, sexual functions in women with OSAS have not yet been studied. AIMS: In this prospective study, we aimed to determine sexual function status in women with OSAS and its relationship with the disease parameters of OSAS. METHODS: Women, who were diagnosed with OSAS with polysomnography performed in the sleep center of our university hospital, formed the study population. Women with any genital deformity, postmenopausal women, and women without a regular partner were excluded from the study. General demographic properties, medical histories, polysomnography parameters, and frequency of intercourse per month were noted for each patient. Patients completed the Sexual Function Questionnaire Version 2 (SFQ-V2) and Epworth Sleepiness Scale. The patients were grouped as mild, moderate, and severe OSAS according to the level of respiratory disturbance index (RDI). MAIN OUTCOME MEASURES: Scores of sexual function domains were determined from SFQ, and their relationships with parameters of polysomnography and demographics were studied. RESULTS: Twenty-five patients were included in the study. Mean age was 48.1 +/- 2.7 years. All were married with a mean marriage duration of 25.6 +/- 3.3 years. Mean frequency of intercourse per month was 3.3 +/- 1.8. All domains of sexual functions except pain and enjoyment significantly decreased with increasing severity of OSAS. When we controlled for factors of age and co-morbid diseases, correlation analyses showed significant negative correlation between levels of RDI and all domains of sexual functions except pain and enjoyment (P < 0.05). CONCLUSIONS: Obstructive sleep apnea syndrome negatively impacts sexual function in women independent of age and associated co-morbid diseases.

Urethral injury as a complication of isolated diastasis pubis: case report.

Diastasis of the symphysis pubis is typically associated with straddle-type pelvic trauma. A case of diastasis pubis due to a recreational water-ski accident is described here. This case is complicated with a partial urethral rupture.

Effect of doxazosin with and without rho-kinase inhibitor on human corpus cavernosum smooth muscle in the presence of bladder outlet obstruction.

PURPOSE: We investigated the relationship of adrenergic responses in corpus cavernosum tissues in the presence of BOO using the alpha1-adrenergic receptor antagonist doxazosin (Pfizer, New York, New York) and the rho-kinase inhibitor Y-27632 (Calbiochem, San Diego, California). MATERIALS AND METHODS: CCSM tissue was obtained from patients who underwent penile prosthesis implantation. Patients were divided into 2 groups according to the presence of BOO. The submaximal (EC80) concentration of phenylephrine (Sigma Chemical Co., St. Louis, Missouri) was calculated by evaluating adrenergic activity responses with cumulatively applied phenylephrine. After achieving a stable contraction plateau test compounds were put in an organ bath. The relaxant potencies of doxazosin and Y-27632 were expressed as the percent of inhibition of the contraction plateau induced EC80 concentration of phenylephrine. Relaxation responses in the 2 groups were compared. RESULTS: At the highest dose of increasing concentrations phenylephrine generated 70% more contraction response in the BOO positive group than in the BOO negative group. Doxazosin and Y-27632 caused concentration dependent relaxation in CCSM precontracted by phenylephrine. With doxazosin significantly higher relaxation responses were attained in the BOO positive group in terms of log IC50 and the maximal relaxation response (p = 0.0353 and 0.0003, respectively). Maximum relaxation responses following Y-27632 administration were significantly higher in the BOO positive group. CONCLUSIONS: The contractility of human corpus cavernosum is increased in the presence of BOO. Doxazosin and Y-27632 generate effective CCSM relaxation in the presence of BOO. Doxazosin and Y-27632 may be the alternatives for the treatment of erectile dysfunction associated with BPH.