The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice.

Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging. A multi-disciplinary panel from BSSM reviewed the available literature on TD and provide evidence-based statements for clinical practice. Evidence was derived from Medline, EMBASE and Cochrane searches on hypogonadism, testosterone therapy (T Therapy) and cardiovascular safety from May 2017 to September 2022. This revealed 1,714 articles, including 52 clinical trials and 32 placebo-controlled randomised controlled trials. A total of twenty-five statements are provided, relating to five key areas: screening, diagnosis, initiating T Therapy, benefits and risks of T Therapy, and follow-up. Seven statements are supported by level 1 evidence, eight by level 2, five by level 3, and five by level 4. Recent studies have demonstrated that low levels of testosterone in men are associated with increased risk of incident type 2 diabetes mellitus, worse outcomes in chronic kidney disease and COVID 19 infection with increased all-cause mortality, along with significant quality of life implications. These guidelines should help practitioners to effectively diagnose and manage primary and age-related TD.

Anterior Urethroplasty for the Management of Urethral Strictures in Males: A Systematic Review.

OBJECTIVE: To identify the currently utilised techniques of anterior urethroplasty described in literature for treatment of urethral strictures, assess the effectiveness of the identified techniques based on re-stricture and complication rates, evaluate, and suggest treatment options based on current evidence for urethral strictures at different locations and of different lengths. METHODS: A systematic review of the MEDLINE, EMBASE, Scopus and Cochrane Library databases from conception up to September 2020 was performed. Primary outcomes included success rates measured via re-stricture rates and the post-operative maximum urinary flow rate (Qmax). Secondary outcomes included patient reported complication rates. RESULTS: A total of 52 papers, including 7 RCTs, met the inclusion criteria. Forty studies described the use of free graft urethroplasty with a median success rate of 86.5% (IQR = 8.1). The best outcomes were found in dorsal onlay buccal mucosa grafting in the penile urethra (86.6%). Twelve described the use of pedicled flap urethroplasty with a median success rate of 76% (IQR = 14.4). Excision and Primary Anastomosis results were reported in 5 studies and showed an overall highest success rate of 89.7% (IQR = 7.0) but involved the shortest strictures of median lengths of 2.1 cm (IQR = 0.48). CONCLUSION: Graft urethroplasty showed optimal outcomes when utilised in penile and bulbar strictures, with dorsal onlay buccal mucosa grafting presenting with the largest evidence base and best outcomes overall. Flap urethroplasty had the highest success rates in panurethral and bulbar strictures, while anastomotic urethroplasty had the greatest success in bulbar and penobulbar strictures.

UK practice for penile prosthesis surgery: baseline analysis of the British Association of Urological Surgeons (BAUS) Penile Prosthesis Audit.

OBJECTIVES: To undertake a prospective multicentre national audit of penile prosthesis practice in the UK over a 3-year period. PATIENTS AND METHODS: Data were submitted by urological surgeons as part of the British Association of Urological Surgeons Penile Prosthesis National Audit. Patients receiving a penile prosthesis (inflatable or malleable) were included as part of a prospective registry over a 3-year period. Data were validated and then analysed using a software package (Tableau). RESULTS: A total of 1071 penile prosthesis procedures were included from 22 centres. The three commonest aetiological factors for erectile dysfunction were diabetes, prostate surgery and Peyronie's disease. Of the recorded data, inflatable penile prostheses were the commonest devices implanted, with 665 devices used (62.1%), whereas malleable prostheses accounted for 14.2% of the implants. Recorded intra-operative complications included urethral injury (0.7%, n = 7), corporal perforation (1.1%, n = 12) and cross-over (0.6%, n = 6). Known postoperative complications were recorded in 9.8% of patients (74/752), with the two most frequently reported being postoperative penile pain (n = 11) and scrotal haematoma (n = 14). CONCLUSION: This baseline analysis is the largest prospective registry of penile prostheses procedures to date. The data show that, over the 3-year collection period in the UK, there are now fewer surgeons performing the procedure, together with a reduction in the number of centres. Peri-operative complications were infrequent, and the rate of implant abortion (e.g. as a result of urethral injury) was very low. Further follow-up data will be required to publish long-term outcomes and patient satisfaction.

Tissue response to applied loading using different designs of penile compression clamps.

Background: Penile compression devices (PCD) or clamps are applied to compress the urethra and prevent urinary incontinence (UI). PCDs are more secure and less likely to leak than pads, allowing men the opportunity to participate in short-term, vigorous activities. However, they are uncomfortable, can cause pressure ulcers (PU) and affect penile blood flow. No objective assessment of tissue health has been undertaken to assess and compare different PCD designs and to provide guidance on safe use. Objective: This study was designed to evaluate existing PCDs in terms of their physiological response and potential for pressure-induced injury. Design, setting and participants: Six men with post-prostatectomy UI tested four selected PCDs at effective pressures, in a random order, in a controlled laboratory setting. Outcome measurements and statistical analysis: Using objective methods for assessing skin injury, PCDs were measured in situ for their effects on circulatory impedance, interface pressures and inflammatory response. Results and limitations: There was evidence for PCD-induced circulatory impedance in most test conditions. Interface pressures varied considerably between both PCDs and participants, with a mean value of 137.4±69.7 mmHg. In some cases, penile skin was noted to be sensitive to loading with elevated concentration of the cytokine IL-1α after 10 mins wear, indicating an inflammatory response. IL-1α levels were restored to baseline 40 mins following PCD removal. Conclusion: Skin health measures indicated tissue and blood flow compromise during the 50 mins of testing using all PCDs. Although there was an elevation in pro-inflammatory cytokines, PCDs did not cause sustained irritation and skin health measures recovered 40 mins after PCD removal. This research indicates that application of a clamp for one hour with an equal clamp free time before reapplication is likely to be safe. Longer periods are often recommended by manufacturers but have yet to be tested.

Redo-urethroplasty for the management of recurrent urethral strictures in males: a systematic review.

PURPOSE: Redo-urethroplasty is a challenge for any genitourethral surgeon, with a number of techniques previously described. This systematic review aims to identify the surgical techniques described in the literature and evaluate the evidence for their effectiveness in managing recurrent urethral strictures. MATERIALS AND METHODS: A systematic review of the MEDLINE and EMBASE databases from 1945 to July 2018 was performed and the urethroplasty procedures were classified according to the site and surgical technique. Primary outcomes included success rates measured via re-stricture rates and the post-op maximum urinary flow rate. Secondary outcomes included complication rates and patient-reported quality of life. RESULTS: A total of 39 identified studies met the inclusion criteria. Twenty-two studies described the use of excision and primary anastomotic urethroplasty with success rates showing wide variability (58-100%). Success rates reported according to the site of the stricture also varied: bulbar (58-100%) and posterior (69-100%) recurrent strictures. One-stage substitution urethroplasty was described in 25 studies with success rates of 18-100%, with the best outcomes reported for bulbar (58-100%) and hypospadias-related (78.6-82%) strictures. Two-stage substitution urethroplasty was described in 12 studies with the success rates of 20-100%, with the best evidence related to hypospadias-related and posterior urethral strictures. The buccal mucosa graft was the graft source with the best evidence for substitution urethroplasty (18-100%). CONCLUSIONS: Trends of effectiveness were identified for redo-urethroplasty modalities in different locations. However, the current levels of evidence are limited to small observational studies, highlighting the need for further larger prospective data to evaluate different techniques used for recurrent urethral strictures.

Twenty Years of Plaque Incision and Grafting for Peyronie's Disease: A Review of Literature.

INTRODUCTION: Plaque incision and grafting (PIG) is indicated for men with complex or severe penile curvature and, despite a multitude of incision types and grafting materials having been used, no individual technique has proven superiority. AIM: To assess outcomes following PIG and to understand the operative technique. METHODS: A systematic review was performed to find all relevant studies reporting on use of the PIG technique to correct curvature resulting from Peyronie's disease. Studies were included if they had >40 participants, were written in the English language, and no penile prosthesis was implanted. MAIN OUTCOME MEASURES: Primary outcome measures included deformity correction, erectile dysfunction, and degree of penile lengthening/shortening. Secondary outcome measures included satisfaction, reoperation rate, and complications. RESULTS: Twelve studies were included in the quantitative synthesis, which overall report on the results of 1,025 patients. Careful patient selection was critical, with erectile function requiring assessment with the International Index of Erectile Function (IIEF), subjective patient reports, and consideration of whether erections are pharmacologically aided. There was no evidence of superiority in favor of any particular incision type or grafting material, and absorbable sutures were clearly favored. Postoperatively, 4.6%-67.4% required pharmacologically aided erections and 0-11.8% were completely unable to achieve erections. Successful straightening occurred in 80.0%-96.4%, although there was no consistent definition of success. Penile length was unchanged in 44.2%-95.0%; 88.0%-92.0% of the patients were satisfied, and .7%-4.7% required reoperation. Altered sensation occurred in 2.0%-22.5% of patients, of which 80.0%-100.0% was only a transient loss. All outcomes were heterogeneously reported. There are no clear predictive factors for erectile dysfunction following PIG surgery. No single incision type or grafting material has proven superiority. CONCLUSION: PIG is an effective and safe technique for correction of complex or severe penile curvature in terms of satisfaction, length change, straightening, and complications. Rice PG, Somani BK, Rees RW. Twenty Years of Plaque Incision and Grafting for Peyronie's Disease: A Review of Literature. Sex Med 2019;7:115-128.

British Association of Urological Surgeons (BAUS) consensus document for the management of male genital emergencies - testicular trauma.

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus comprising British Association of Urological Surgeons (BAUS) Section of Andrology and Genitourethral Surgery together with experts from units throughout the UK. Testicular trauma requires prompt investigation and treatment in order to prevent the development of subfertility or hypogonadism. This series of consensus statements provide guidance for UK practice.

British Association of Urological Surgeons (BAUS) consensus document for the management of male genital emergencies - penile fracture.

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. The aim of these consensus statements is to provide best practice guidance for urological surgeons based in the UK which are developed by an expert consensus. Penile fracture is a rare emergency and in most cases requires prompt exploration and repair to prevent erectile dysfunction and penile curvature.

British Association of Urological Surgeons (BAUS) consensus document for the management of male genital emergencies - penile amputation.

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus committee comprising members of the British Association of Urological Surgeons (BAUS) Section of Andrology and Genitourethral Surgery together with experts from urology units throughout the UK. Penile amputation is a rare genital emergency, which requires prompt intervention and microsurgical reconstruction. The consensus statements will outline the management of these cases for non-specialist units, as well as recommendations for reconstruction for specialists.

BAUS consensus document for the management of male genital emergencies: priapism.

Male genital emergencies relating to the penis and scrotum are rare and require prompt investigation and surgical intervention. Clinicians are often unfamiliar with the management of these conditions and may not work in a specialist centre with on-site expertise in genitourethral surgery. A series of consensus statements have been developed by an expert consensus committee comprising members of the BAUS Section of Andrology and Genitourethral Surgery together with experts from urology units throughout the UK. Priapism requires prompt assessment and treatment and these consensus statements provide guidance for UK practice.

Priapism in children: a comprehensive review and clinical guideline.

OBJECTIVE: We review the English literature between 1980 and 2013 and summarize the clinical classification, aetiology, physiology, and pathophysiology of paediatric priapism. We propose a clinical guideline for the management of priapism in children. PATIENTS: Male patients aged ≤ 18 years. RESULTS: Priapism, a prolonged penile erection lasting >4 h, is a rare condition in childhood. There are 3 widely accepted types of priapism: 1) ischaemic priapism, the commonest type seen in children; 2) stuttering priapism, recurrent, self-limiting prolonged erections; and 3) non-ischaemic priapism, rare in children, usually due to trauma. Neonatal priapism has also been described. Ischaemic priapism is a urological emergency causing fibrosis of the corpora cavernosa, subsequent erectile dysfunction and penile disfigurement. The commonest causes of priapism in children are sickle cell disease (65%), leukaemia (10%), trauma (10%), idiopathic (10%), and pharmacologically induced (5%). CONCLUSIONS: Priapism in children must be assessed urgently. Rapid resolution of ischaemic priapism prevents permanent cavernosal structural damage and is associated with improved prognosis for potency later in life. Stuttering priapism requires careful counselling for episodic management. Chronic prophylaxis may be obtained using α-adrenergic sympathomimetics, phosphodiesterase type 5 inhibitors and, in sickle cell disease, hydroxyurea. Non-ischaemic and neonatal priapism may generally be treated less urgently.

Treatment of carcinoma in situ of the glans penis with topical chemotherapy agents.

BACKGROUND: The use of topical agents in the treatment of carcinoma in situ (CIS) of the penis has been well described in the literature. Previous studies have been limited by small sample size and imprecise end points. OBJECTIVE: Establish the response rate of 5-fluorouracil (5-FU) and imiquimod (IQ) in the treatment of penile CIS in a large contemporary series in a supranetwork centre. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all primary and recurrent cases of penile CIS treated with 5-FU and IQ identified from a prospective database over a 10-yr period. Therapy was standardised in all cases with application to the lesion for 12h every 48 h for 28 d. INTERVENTION: 5-FU was the first-line therapy, and IQ was the second-line topical agent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was defined as complete response (CR; i.e., resolution of lesion), partial response (PR; i.e., lesion reduced in size and or visibility), or no response (NR; ie, no improvement in lesion size and or visibility). The secondary end points included local toxicity and adverse events. No statistical analysis or software was used. RESULTS AND LIMITATIONS: A total of 86 patients were diagnosed with CIS of the penis over the 10-yr period. Forty-four (51%) received topical chemotherapy. The mean follow-up was 34 mo. CR to topical chemotherapy was seen in 25 (57%), PR was seen in 6 (13.6%), and NR was seen in the remaining 13 (29.5%) patients. Local toxicity was experienced by 10% of patients, and 12% had an adverse event following application of 5-FU. The retrospective design and short follow-up were the major limitations of this study. CONCLUSIONS: Topical chemotherapy agents are moderately effective first-line therapy in the treatment of penile CIS. Toxicity and adverse events were few with our treatment protocol. The issues of long-term surveillance and assessment of partial responders remain a challenge. Topical chemotherapy should remain a first-line treatment option for penile CIS.

Paraganglioma of the spermatic cord: case report and review of the literature.

Paragangliomas rarely involve the genitourinary tract. We present a case of a paraganglioma arising from the spermatic cord and review the literature on the topic.

Y-27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells.

PURPOSE: Benign prostatic hyperplasia (BPH) causes mechanical urinary flow obstruction by 2 components, namely an enlarged prostate (static component) and elevated smooth muscle tone (dynamic component). Currently available treatments for BPH aim to inhibit the proliferation of prostatic cells or decrease the elevated tone. To our knowledge no single agent that can achieve these 2 ends has yet been identified. A specific inhibitor of Rho-kinase, Y-27632 ((+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride), has been demonstrated to cause smooth muscle relaxation and inhibit smooth muscle cell proliferation. Therefore, we investigated the effect of Y-27632 on prostatic smooth muscle proliferation and tone. MATERIALS AND METHODS: Rho-kinase expression was investigated by immunocytochemistry and immunoblotting in smooth muscle cells obtained from rat and human prostates. The effect of Y-27632 was examined on the proliferation of these cells and on the contractions elicited by electrical field stimulation and exogenous phenylephrine in rat prostatic strips. RESULTS: Immunoblot and immunofluorescence analysis showed that Rho-kinase is present in the cytosol and located in the perinuclear region in human and rat prostatic smooth muscle cells. Y-27632 decreased the proliferation of human and rat prostatic smooth muscle cells, and inhibited noradrenergic contractions elicited by electrical field stimulation and exogenous phenylephrine in rat prostatic strips (EC50 17.8 +/- 4.8 and 7.8 +/- 2.1 microM, respectively). CONCLUSIONS: To our knowledge we report the first demonstration of the presence of Rho-kinase in prostatic smooth muscle cells, and of the relaxant and antiproliferative effect of a Rho-kinase inhibitor. We suggest a novel use for Rho-kinase inhibitors in the treatment of BPH as a single agent with dual action.

BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitro.

PURPOSE: In cavernous smooth muscle nitric oxide (NO) activates soluble guanylate cyclase, which catalyzes the synthesis of cyclic guanosine 3',5'-monophosphate, leading to smooth muscle relaxation, increased blood flow and penile erection. The pyrazolopyridine derivative BAY41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4ylamine) was identified and found to stimulate soluble guanylate cyclase in a NO independent manner. We investigated the effect of BAY41-2272 on human and rabbit corpus cavernosum. MATERIALS AND METHODS: We investigated the effect of BAY41-2272 on the tone and nitrergic relaxation responses of human and rabbit cavernous strips in the absence and presence of the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4-3a]quinoxalin-1-one) or the NO synthase inhibitor L-NAME (N-nitro-L-arginine-methyl ester HCl). The potency of BAY41-2272 was compared to that of another soluble guanylate cyclase activator YC-1, and the NO releasing compound spermine NONOate (N-2-aminoethyl-N-2-hydroxy-2-nitrosohydroazino-1,2-ethylenediamine). RESULTS: BAY41-2272 resulted in concentration dependent relaxation of human and rabbit cavernosum (mean EC50 +/- SEM 489.1 +/- 22.5 and 406.3 +/- 21.5 nM., respectively). The compound was 32 times more potent than YC-1 and twice as potent as spermine-NONOate. ODQ decreased the potency of BAY41-2272, such that in the presence of 30 microM. ODQ the EC50 of BAY41-2272 induced relaxation was 1,407.3 +/- 158.0 and 1,902.7 +/- 11.0 nM. in human and rabbit tissues, respectively. L-NAME also inhibited relaxations elicited by BAY41-2272 in rabbit tissue. In the presence of 500 microM. L-NAME the EC50 of BAY41-2272 induced responses was 836.7 +/- 46.7 nM. BAY41-2272 at subthreshold concentrations of 30 to 50 nM. potentiated nitrergic responses. Moreover, the inhibition of nitrergic responses by L-NAME was reversed by 0.3 to 3 microM. BAY41-2272. CONCLUSIONS: We report that a nonNO based soluble guanylate cyclase activator relaxes human and rabbit corpus cavernosum, and potentiates nitrergic responses.

A Rho-kinase inhibitor, soluble guanylate cyclase activator and nitric oxide-releasing PDE5 inhibitor: novel approaches to erectile dysfunction.

Approximately 50% of men aged over 40 suffer from male erectile dysfunction. Treatment options have widened since the launch of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate (Viagra trade mark ). However, a certain portion of the patient population, such as diabetics, do not gain significant benefit from PDE5 inhibitors, possibly due to a lack of endogenous nitric oxide. Therefore, new treatment modalities based on the absence of endogenous nitric oxide have been developed. Among them are Rho-kinase inhibitors, soluble guanylate cyclase activators and nitric oxide-releasing PDE5 inhibitors. The available data concerning these compounds will be summarised and their therapeutic potential for male erectile dysfunction will be discussed.