Testosterone castration levels in patients with prostate cancer: Is there a difference between GnRH agonist and GnRH antagonist? Primary results of an open-label randomized control study.

PURPOSE: To compare testosterone castration levels between patients treated with the gonadotropin-releasing hormone (GnRH) antagonist, degarelix, and GnRH agonist. MATERIALS AND METHODS: Patients with prostate cancer (PCa) of a single outpatient clinic were randomized (2:1) to receive degarelix (group A) or GnRH agonist (group B). The study evaluated testosterone and prostate-specific antigen (PSA) levels, patients' age, Gleason score and the presence of metastases (nodal or bone). Testosterone and PSA levels were measured at 1st, 6th, 12th, and 18th months. Mann-Whitney test and Spearman correlation were used to investigate independent variable while standard multiple regression was performed to explore statistically significant correlations. Kruskal-Wallis test was used to compare testosterone levels at follow-up. RESULTS: The study included 168 patients, 107 in group A and 61 in group B. Testosterone levels at 1st month were significantly lower in patients under GnRH antagonist than those receiving GnRH agonist (group A: 22 ng/dL vs. group B: 29 ng/dL, p=0.011). However, PSA values did not differ significantly between groups (group A: 0.130 ng/mL vs. group B: 0.067 ng/mL, p=0.261). In multivariate analysis, treatment with degarelix was an independent factor of lower testosterone levels at 1st month (p=0.013). Comparison of testosterone levels at 6, 12, and 18 months did not reveal any significant difference within each group. CONCLUSIONS: In patients with PCa who are candidates for androgen deprivation therapy, the administration of GnRH antagonist seems to achieve significantly lower testosterone levels compared to treatment with GnRH agonist at 1st month of treatment.

Methylation of PCDH17 and NEFH as prognostic biomarker for nonmetastatic RCC: A cohort study.

DNA methylation makes up a main part of the molecular mechanism of cancer evolution and has shown promising results in the prognosis of renal cell cancer (RCC). In this study, we investigated the possible association of promoter methylation of PCDH17, NEFH, RASSF1A, and FHIT, genes with the prognosis of nonmetastatic RCC patients. Cancerous and normal adjacent tissues from surgical specimens of 41 patients with long follow-up were treated for DNA isolation and bisulfite conversion. The gene promoter methylation was determined with quantitative methylation-specific PCR (qMSP). Wilcoxon signed-rank test was used for paired methylation comparisons, while univariate linear regression and Mann-Whitney test were applied for associating methylation status with clinical and disease characteristics. Cox regression proportional hazards models and Kaplan-Meier plots were used for survival analyses in reference to methylation status. Paired comparisons showed tissue-specific hypermethylation for PCDH17 (P < .001), NEFH (P < .001), RASSF1A (P = .032), while a positive association of methylation in normal tissues with age was demonstrated for PCDH17 (P < .001), RASSF1A (P < .001), FHIT (P < .001). PCDH17 was more methylated in cases with clear cell RCC (P = .015) and high-grade tumor (P = .013), while NEFH methylation was higher in locally advanced cases (P = .032). PCDH17 hypermethylation in cancerous and normal tissues was linked to shorter disease-specific survival (DSS, P = .026, P = .004), disease-free survival (DFS, P = .004, P = .019) while NEFH hypermethylation in cancerous tissues was related to shorter DSS (P = .032). Increased methylation difference of NEFH was also associated with shorter DSS (P = .041) and DFS (P = .020), while the corresponding parameter for PCDH17 was associated with poor DFS (P = .014). Kaplan-Meier curves for hypermethylation in cancer tissues demonstrated different clinical courses for PCDH17 (P = .017), NEFH (P = .023) regarding DSS, and PCDH17 (P = .001) regarding DFS. Our study not only highlights the prognostic value of promoter methylation of PCDH17 and NEFH in cancer tissues but also is the first report of the prognostic value of methylation alterations in normal tissues. Our findings are the first report of the prognostic value of methylation alterations in normal tissues, which can contribute to improved assessment of recurrence risk.

The effect of statins on semen parameters in patients with hypercholesterolemia: A systematic review.

BACKGROUND: Statins constitute the mainstay of treatment in patients with hypercholesterolemia. However, their effect on semen parameters is unknown. OBJECTIVE: This study aimed to systematically review the best available evidence regarding the effect of statins on ejaculate volume and sperm concentration, motility, morphology, or vitality. MATERIALS/METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to January 10, 2021. Either randomized-controlled trials or prospective cohorts, conducted in males with hypercholesterolemia, were included. RESULTS: Four studies, published between 1992 and 2014, were eligible. The number of participants ranged from 8 to 120 (n = 161). Study duration ranged from 14 to 48 weeks. The type and dose of statin used were pravastatin 20-80 mg/day and simvastatin 20-40 mg/day. With regard to ejaculate volume (n = 3) and sperm concentration (n = 4), no effect was shown with either pravastatin or simvastatin. Regarding sperm motility, either an increase (n = 2; pravastatin, simvastatin), decrease (n = 1; pravastatin), or no effect (n = 1; pravastatin, simvastatin) was found. With respect to sperm morphology, either a decrease (n = 2; pravastatin, simvastatin) or no effect (n = 2; pravastatin, simvastatin) was shown. Concerning sperm vitality, a single study showed a decrease with simvastatin. Because of the high heterogeneity of the populations studied and the limited number of studies, a meta-analysis was not performed. CONCLUSION: This is the first systematic review on the effect of statins on semen parameters. As there is no evidence for such a detrimental effect, no specific approach has to be suggested regarding the preservation of reproductive function in men with hypercholesterolemia.

Calculating interfractional prostate motion during radiation therapy course using fiducial markers.

PURPOSE: In this study we evaluated the day to day prostate displacement during radiation therapy by using implanted radiopaque fiducials and daily image guided position verification. METHODS: The data of 10 patients that received radiation therapy to the prostate were analyzed. Three fiducial markers were implanted in the prostate before treatment initiation for everyday verification of the target's position. Daily X ray images (kilovolt/KV films) of the pelvis were acquired for verification and were matched with baseline images produced during treatment preparation using bony structures and fiducials as landmarks. We calculated the mean difference between the two methods and the prostate displacement derived from these measurements. RESULTS: A total of 208 KV films were obtained. Our results showed a non-uniform prostate motion, with most of the displacements observed in the caudal direction followed by anterior, posterior, cranial, right and left. The mean target motion in each of the above directions was 3.5 mm, 3.5 mm, 3.3 mm, 3.9 mm, 2 mm and 2.4 mm. Based on the cumulative frequency of the target's displacement, a margin of 8 mm, 7mm, 5 mm, 4 mm, 9 mm and 7 mm in the anterior, posterior, left, right, cranial and caudal direction respectively would account for 95% of prostate's motion, provided that every day KV image guidance is performed. CONCLUSION: A non-isotopic margin of 8 mm, 7mm, 5 mm, 4 mm, 9 mm and 7 mm around the prostate can be considered safe for treatment delivery.

Urology during a Crisis: A Management Algorithm.

COVID-19 pandemic has affected more than a million people worldwide causing a public health crisis. Under these unique circumstances, urologists continue to provide essential healthcare services and support healthcare systems, by participating in the treatment of COVID-19(+) patients and sparing vital equipment and hospital beds. However, delivering medical care during the pandemic requires strategic planning for all surgical and outpatient activities. Proposed measures include rescheduling elective non-oncological surgeries and using a prioritization protocol for oncological surgeries according to hospital capacity. Following that, outpatient clinics could be partly replaced by telemedicine. Additionally, urologists should be trained in screening and treating patients with COVID-19 during their daily routine.  In order to efficiently provide their services, a management protocol for suspected or known COVID-19 urological patients should be implemented. Furthermore, preventive measures for the nosocomial dispersion of the virus and training on self-protective equipment is mandatory for all physicians. Finally, organizational planning for the best utilization of the staff is of utmost importance. Implementation and adaptation of the protocols according to local requirements and guidelines will ameliorate the quality of services and population's health status. Finally, enhancement of current practices will prepare health systems for future crisis.

Late results of a randomized trial on the role of mild hypofractionated radiotherapy for the treatment of localized prostate cancer.

Background: Prostate cancer is considered to be highly sensitive to changes in radiation therapy dose per fraction, specifically to hypofractionation. An increase in the fractionation dose could cause a higher increase to the prostate than to the normal tissues leading to better disease control with less toxicity. Here we present the results of a randomized trial comparing mild hypofractionation to conventional fractionation after a median of 3,6 years follow up. Patients and Methods: 139 patients were randomized to receive either hypofractionated radiotherapy with 2,25 Gy/fr to a total of 72 Gy (arm 1) or conventionally fractionated treatment with 2Gy/fr to a total of 74 Gy (arm 2). 72 patients were assigned to arm 1 and 67 to arm 2. Results: After a median follow up of 3,6 years, 23 patients (31,9%) from arm 1 developed grade≥ 2 acute genitourinary toxicity and 21 (31,3%) from arm 2 (p=0,79). The corresponding values from gastrointestinal were 15 (20,8%) and 12 (17,9%) (p=0,6). For late toxicity from GU, 8 patients (11,1%) developed grade≥ 2 symptoms in arm 1 and 7 (10,4%) in arm 2 (p=0,92). late GI toxicity grade≥ 2 was observed in 8 (11,1%) patients in arm 1 and 8 (11,9%) in arm 2 (p=0,88). In multivariate analysis, hormone therapy was significantly associated with late GI events, while acute toxicity from both GU and GI was a prognostic factor of late adverse reaction. Conclusion: No difference in the toxicity profile could be identified between hypofractionation and conventional fractionation. Our schedule of 2,25Gy/fr seems safe and tolerable by the patients with acceptable rates of acute and late toxicity.

Systemic therapy for chromophobe renal cell carcinoma: A systematic review.

BACKGROUND: Chromophobe renal cell carcinoma (chRCC) subtype accounts for almost 5% of total RCC cases. It carries the best prognosis among the rest of RCC types. However, patients with metastatic chRCC disease have worse prognosis than patients with advanced clear cell RCC. Furthermore, available data regarding systemic therapy for chRCC patients are scarce and confusing. AIM: The aim of this systematic review is to search for and critically appraise studies that investigate the results of systemic therapies in patients diagnosed with metastatic chRCC disease. METHODS: Search strategy included PUBMED, CENTRAL, clinicaltrials.gov databases, and abstracts of major conferences with a focus on urologic oncology (till March 2019). Studies investigating patients that were treated with systemic therapy for advanced chRCC disease were included. Primary outcomes were progression-free survival and objective response rate. Secondary outcome was overall survival. Screening of available studies was carried out by 2 groups of reviewers, as well as the quality assessment of the included studies. RESULTS: The systematic search yielded 369 studies, of which 15 studies (2 randomized control trials and 13 cohort studies), involving 183 patients, met the eligibility criteria. The 2 randomized control trials that directly compared sunitinib vs. everolimus, suggested an advantage for sunitinib without being statistically significant. Furthermore, sunitinib seems to be superior than sorafenib at least in terms of objective response rate. Regarding mTOR inhibitors, they may have a role in a specific subset of chRCC patients, that needs to be further explored. Finally, as far as immunotherapy is concerned, available data suggest that chRCC seems to be resistant to recent immune check point inhibitors, since just a few tumor responses were observed with the administered immunotherapy regiments. CONCLUSION: The optimum therapy for metastatic chRCC is still missing, as results from ongoing trials are awaited. More studies, of high quality and adequate sample size, that will be based on the specific biology of chRCC, have to be carried out in order to identify the best treatment.

The impact of burnout and occupational stress on sexual function in both male and female individuals: a cross-sectional study.

Burnout and occupational stress are common problems in the modern society. The aim of the study was to investigate the association of burnout and occupational stress with sexual dysfunction. The study enrolled 251 residents, 143 males and 108 females. The personal medical history, demographics, and professional data of the participants were recorded. The Copenhagen Burnout Inventory (CBI) and the job stress measure were used for the evaluation of burnout and occupational stress, correspondingly. The International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI) were used for the assessment of sexual function. The majority of the respondents were males (57%), with a mean age of 31 years. From the analysis concerning males, personal burnout, hypertension, and alcohol consumption correlated independently with erectile dysfunction (p = 0.001) and reduced total satisfaction (p < 0.001). With respect to the female participants, the number of children was found to be related to easier arousal (p = 0.009), better lubrication (p = 0.006), and orgasm (p = 0.016). Contrariwise, job stress related negatively with lubrication (p = 0.031) and orgasm (p = 0.012). This is the first study examining the effect of burnout on sexual function. Personal burnout was observed to be associated with sexual dysfunction in men whereas job stress correlated with female sexual problems. Further examination in different occupational groups and a greater number of patients is required.

The role of hypofractionated radiotherapy for the definitive treatment of localized prostate cancer: early results of a randomized trial.

Background: Prostate cancer is considered to have a special biology which could affect the radiation therapy result based on the selected fractionation scheme. We present the preliminary results of a randomized trial comparing conventionally and hypofractionated radiation therapy for prostate cancer. Methods: Patients included in the study had localized prostate cancer (cT1c-T3bN0M0) and were randomly assigned to mild hypofractionated (72 Gy in 32 fractions, arm1) or conventionally fractionated (74 Gy in 37 fractions, arm2) radiation therapy treatment with Volumetric Arc Therapy technique. The treatment was delivered only to the prostate with or without the seminal vesicles according to physician's discretion and hormone therapy was optional according to the disease stage and comorbidities. Here we present the preliminary results of acute toxicity from the gastrointestinal (GI) and genitourinary (GU) system. Results: Between 2015 and 2016, 139 patients were enrolled. 67 patients were treated with conventional fractionation and 72 were treated with hypofractionation. Grade≥ 2 toxicity from GU and GI was observed in 23 and 21 patients (31,9% vs 31,3%, p=0,79) and 15 and 12 (20,8% vs 17,9%, p=0,6) for arm1 and arm2 respectively. No statistically significant differences were observed between arms in the incidence of early toxicity. There was no correlation observed between patient characteristics and toxicity from either GU or GI. Conclusions: Hypofractionated radiotherapy appears to be equally tolerated compared to conventional fractionation in the early setting. Longer follow up is needed to assess the late toxicity profile of the patients and any potential differences between the control and experimental arm.

Plexiform Schwannoma of the Penis: A Rare Subtype of Genital Schwannoma.

Schwannomas are benign, encapsulated neurogenic tumors which present in diverse histological subtypes despite the limited variety of their cellular constituents. These include the cellular, ancient, cystic, epithelioid, melanotic, psammomatous, schwannoma with pseudoglandular elements, and plexiform varieties. The plexiform schwannoma (PS) represents 4.3% of all schwannomas. These lesions are commonly encountered in the head and neck region and are extremely rare in the penis. To the best of our knowledge only 34 cases of penile schwannomas have been reported and this is the 3rd case of plexiform penile schwannoma. A 39-year-old patient presented to our andrology outpatient clinic complaining for two painful penile nodules. The lesions were located on the dorsum of the penile shaft. His medical history was insignificant for penile trauma and sexual transmitted diseases. The masses measured 2x1 cm and 0.5x1 cm. After sonographic and magnetic resonance evaluation the patient was admitted to theatre and underwent topical resection of the lesions. Histopathology revealed plexiform schwannoma. Postoperatively, penile tenderness and hyperesthesia ensued which was managed with pregabalin administration and topical corticosteroids. Plexiform schwannomas are rare in the penile region. Surgical excision is inevitably the only way to diagnose and treat the lesions. They must be differentiated by a variety of malignant and benign clinical conditions. Topical excision suffices for oncological control and allows for acceptable functional outcomes.

What are the benefits and harms of testosterone therapy for male sexual dysfunction?-a systematic review.

The role of Testosterone Therapy (TTh) in the management of male sexual dysfunction remains unclear. Objective of the authors was to systematically review the relevant literature assessing the benefits and harms of TTh in men with sexual dysfunction. EMBASE, MEDLINE, Cochrane Systematic Reviews-Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane HTA, DARE, HEED), Google Scholar, WHO international Clinical Trials Registry Platform Search Portal, CINAHL databases and clinicaltrial.gov were searched systematically in March 2015 and an updated search was performed in March 2016. Randomized and non-randomized comparative studies assessing the benefits and harms of TTh in hypogonadal, borderline eugonadal and eugonadal men suffering from sexual dysfunction were included. Risk of bias and confounding assessments were performed. A narrative synthesis was undertaken. Of the 6410 abstracts identified, 36 studies were judged to be eligible for inclusion, including 25 randomized clinical trials (RCTs) and 11 non-randomized comparative studies (NRCSs), recruiting a total of 4944 patients. RCTs were judged to have low or unclear risk of bias, while NRCSs had high risk of bias and thus, overall quality of evidence was judged to be at least unclear. Based on the evidence mainly provided by the RCTs included in this systematic review, TTh could be considered for men with low or low-normal testosterone levels and problems with their sexual desire, erectile function and satisfaction derived from intercourse and overall sexual life. The exact testosterone formulation, dosage and duration of treatment remain to be clarified, while the safety profile of TTh also remains unclear. TTh could be used with caution in hypogonadal and most probably borderline eugonadal men to manage disorders of sexual desire, erectile function and sexual satisfaction. The overall low-to-moderate evidence quality highlights the need for robust and adequately designed clinical trials.

The impact of Diabetes Mellitus on Lower urinary tract symptoms (LUTS) in both male and female patients.

INTRODUCTION: Contemporary studies examine the connection of Diabetes Mellitus (DM) with Lower urinary tract symptoms (LUTS), alone or associated with other factors of the metabolic syndrome. However, little research has occurred concerning patients with diabetes of both genders and sexes without other diseases of the lower urinary tract. The aim of this study is to examine the relationship between DM and LUTS. METHODS: The study enrolled 110 patients with DM and 134 healthy individuals. The IPSS questionnaire was used for the evaluation of symptoms from lower urinary tract. Data was analyzed with univariate and multivariate logistic regression using SPSS v.24. RESULTS: Analysis with moderate/severe LUTS as dependent variable and plausible confounding factors (age group, BMI, hypertension, dyslipidemia, years with DM and reported HbA1c) as covariates revealed that only HbA1c levels correlated independently with the presence of moderate/severe LUTS (p = 0,024, OR:2,729, CI:1,144-6,509) in diabetic women, while there was no statistically significant difference between male groups. HbA1c levels' correlation with IPSS-voiding and IPSS- storage score was not statistically significant. Quality of life is also affected in women with diabetes mellitus (p: 0,02). CONCLUSION: Only an increase in HbA1c was independently connected with a deterioration of LUTS in the female group.

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Treatment of erectile dysfunction is based on pharmacotherapy for most patients. AIM: To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. METHODS: A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Ten recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A). (iii) PDE5 inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use (LE = 3, GR = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v) Intracavernosal injection therapy with alprostadil should be offered to patients as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi) Intraurethral and topical alprostadil are effective and well-tolerated treatments for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and topical alprostadil should be considered second-line therapy for erectile dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5 inhibitors to the maximum tolerated dose is strongly recommended because it increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix) Treatment selection and follow-up should address the psychosocial profile and the needs and expectations of a patient for his sexual life. Shared decision making with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x) Counterfeit medicines are potentially dangerous. It is strongly recommended that physicians educate their patients to avoid taking any medication from unauthorized sources (LE = 2, GR = A). The first seven recommendations are the same as those from the Third International Consultation for Sexual Medicine and the last three are new recommendations. CONCLUSION: PDE5 inhibitors remain a first-line treatment option because of their excellent efficacy and safety profile. This class of drugs is continually developed with new molecules and new formulations. Intracavernosal injections continue to be an established treatment modality, and intraurethral and topical alprostadil provide an alternative, less invasive treatment option.

Current role of local treatments for erectile dysfunction in the real-life setting.

PURPOSE OF REVIEW: Local treatments for erectile dysfunction include intraurethral alprostadil as well as topical alprostadil cream. They are alternative treatment options to oral or intracavernosal treatments that could overcome unmet needs in patient treatment. RECENT FINDINGS: Intraurethral and topical alprostadil are two local methods of delivering an erectogenic drug to the patient. They have an established efficacy and a safety profile without important systemic adverse events. Efficacy data show that they result in significantly improved erections sufficient for sexual intercourse compared with placebo. Comparative efficacy data to other treatments are very limited. There are no specific contraindications to other drugs. They can be offered to patients who do not tolerate or do not respond to oral treatment. They can be also combined to oral treatment as a salvage therapy before proceeding to intracavernosal injections. The major advantages of them are the patient-friendly modality of delivering and the presence of minor local adverse events that are self-limited and mild in nature. Priapism or prolonged erections are very rare with local treatments. SUMMARY: Local treatments can have an important role as a first-line treatment for erectile dysfunction or in drug combinations mainly because of their excellent safety profile.

How to treat erectile dysfunction in men with diabetes: from pathophysiology to treatment.

Erectile dysfunction (ED) is highly prevalent affecting at least 50 % of men with diabetes mellitus (DM). DM may cause ED through a number of pathophysiological pathways. These include neuropathy, endothelial dysfunction, cavernosal smooth muscle structural/functional changes, and hormonal changes. Lifestyle changes, diabetes control, and treatment of hypogonadism are important as the first step in ED management since there is no curative treatment for ED. Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment option. Intracavernous administration of vasoactive drugs is commonly used as a second-line medical treatment when PDE5i have failed. Alprostadil is the most widely used drug in this second-line setting. The combination of papaverine, phentolamine, and alprostadil represents the most efficacious intracavernous pharmacologic treatment option that may save non-responders to alprostadil. Penile prosthesis implantation can be considered in treatment refractory cases, with excellent functional and safety results in the properly informed patients.

A review of the use of tadalafil in the treatment of benign prostatic hyperplasia in men with and without erectile dysfunction.

Epidemiological data link erectile dysfunction (ED) and benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS), two highly prevalent conditions in aging men, assuming common pathophysiological pathways. Tadalafil 5 mg once daily has been approved for the treatment of men with LUTS with or without comorbid ED. The aim of this review is to provide an overview of current knowledge on the epidemiological and pathophysiological links between ED and LUTS and to focus on tadalafil as a new treatment option in men with BPH-associated LUTS. A Medline search was completed using the Medical Subject Headings (MESH® keywords) 'prostatic hyperplasia' and 'phosphodiesterase inhibitors'. This search revealed 125 relevant references (entire Medline database up to 11 March 2014). The efficacy of tadalafil 5 mg once daily for the treatment of LUTS has been reported by several well-designed studies. Tadalafil improves significantly the total International Prostate Symptom Score (IPSS), the voiding and storage subscores, the IPSS Quality of Life (QoL) and the BPH Impact Index (BII). Its efficacy is irrelevant to the erectile function status of the patients. However, in the majority of these studies tadalafil is not associated with improvement in maximum urine flow or post-void residual volume (PVR). Its safety profile is well established and no new or unexpected adverse events other than those reported in ED studies have been recorded. Tadalafil is today a new treatment alternative to other established drugs for LUTS such as the α-adrenergic antagonists or 5α-reductase inhibitors. However, it is not just an alternative, since sexual adverse events associated with these drugs are avoided and tadalafil is the only drug that can treat both ED and LUTS at the same time.

European Association of Urology guidelines on priapism.

CONTEXT: Priapism is defined as a penile erection that persists beyond or is unrelated to sexual interest or stimulation. It can be classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent or intermittent). OBJECTIVE: To provide guidelines on the diagnosis and treatment of priapism. EVIDENCE ACQUISITION: Systematic literature search on the epidemiology, diagnosis, and treatment of priapism. Articles with highest evidence available were selected to form the basis of these recommendations. EVIDENCE SYNTHESIS: Ischaemic priapism is usually idiopathic and the most common form. Arterial priapism usually occurs after blunt perineal trauma. History is the mainstay of diagnosis and helps determine the pathogenesis. Laboratory testing is used to support clinical findings. Ischaemic priapism is an emergency condition. Intervention should start within 4-6h, including decompression of the corpora cavernosa by aspiration and intracavernous injection of sympathomimetic drugs (e.g. phenylephrine). Surgical treatment is recommended for failed conservative management, although the best procedure is unclear. Immediate implantation of a prosthesis should be considered for long-lasting priapism. Arterial priapism is not an emergency. Selective embolization is the suggested treatment modality and has high success rates. Stuttering priapism is poorly understood and the main therapeutic goal is the prevention of future episodes. This may be achieved pharmacologically, but data on efficacy are limited. CONCLUSIONS: These guidelines summarise current information on priapism. The extended version are available on the European Association of Urology Website (www.uroweb.org/guidelines/). PATIENT SUMMARY: Priapism is a persistent, often painful, penile erection lasting more than 4h unrelated to sexual stimulation. It is more common in patients with sickle cell disease. This article represents the shortened EAU priapism guidelines, based on a systematic literature review. Cases of priapism are classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent). Treatment for ischaemic priapism must be prompt in order to avoid the risk of permanent erectile dysfunction. This is not the case for arterial priapism.

Adherence to initial PDE-5 inhibitor treatment: randomized open-label study comparing tadalafil once a day, tadalafil on demand, and sildenafil on demand in patients with erectile dysfunction.

INTRODUCTION: Phosphodiesterase type 5 (PDE-5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen. AIM: To evaluate the effects of initiating treatment with tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or sildenafil PRN on treatment adherence. METHODS: In this multicenter, open-label study, men (≥ 18 years) with ED, naïve to PDE-5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8-week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed). MAIN OUTCOME MEASURES: Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan-Meier product-limit method. Treatment-group differences were estimated as hazard ratio (HR; Cox proportional hazards). RESULTS: Seven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan-Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups (P < 0.05) included "lack of efficacy (duration of erection)" (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), "time constraints due to short window of action" (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and "feel medication controls my sexual life" (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group differences were found in International Index of Erectile Function-Erectile Function domain change from baseline to end of RT (least squares mean: 9.4-10.0, P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common adverse event (≥ 4%) was headache. CONCLUSIONS: ED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups.

Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study.

INTRODUCTION: Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, is approved for treating signs and symptoms of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED); tamsulosin, an alpha-blocker, is approved for treating signs and symptoms of BPH. AIM: To determine the effects of tadalafil or tamsulosin on sexual function, including ejaculation and orgasm, satisfaction, and erectile function, in sexually active men with ED and lower urinary tract symptoms suggestive of BPH (LUTS/BPH). METHODS: A randomized, double-blind, placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH; tamsulosin 0.4 mg once daily was an active control. MAIN OUTCOME MEASURES: The International Index of Erectile Function (IIEF) questionnaire was administered at baseline and 4, 8, and 12 weeks. Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function (OF) domain (IIEF-Q9 [ejaculatory frequency] and Q10 [orgasmic frequency]). Other measures included IIEF-Intercourse Satisfaction (IS), Overall Satisfaction (OS), and Erectile Function (EF) domains. Changes from baseline to 12 weeks (or last observation) vs. placebo were analyzed using analysis of covariance. Higher IIEF scores indicate better functioning. RESULTS: Of 511 study participants, 310 (60.7%) had ED and were sexually active. The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo (P = 0.048), as did IIEF-Q9 (P = 0.045) but not IIEF-Q10 (P = 0.100). Compared with placebo, IIEF-OF, Q9, and Q10 decreased significantly with tamsulosin (all P < 0.05). The IIEF-IS and OS increased significantly at end point with tadalafil (both P < 0.001); for tamsulosin, change was not significant for IS, while OS decreased significantly (P = 0.009). The IIEF-EF domain increased significantly vs. placebo with tadalafil (P < 0.001) but not tamsulosin (P = 0.699). CONCLUSIONS: Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo, with no significant effect on erectile function.