Clomiphene citrate: A potential alternative for testosterone therapy in hypogonadal males.

BACKGROUND: Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off-label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. METHODS: In this single-centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. RESULTS: In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. CONCLUSION: Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.

Study protocol for a parallel-group randomized controlled multi-center trial evaluating the additional effect of continuous ultrasound bladder monitoring in urotherapy for children with functional daytime urinary incontinence (SENS-U trial).

BACKGROUND: Lower urinary tract dysfunction or functional urinary incontinence is a common condition with a prevalence up to 21% between 6 and 8 year-old children. It is associated with an impaired quality of life, lower self-esteem, and social stigmatization. Urotherapy is the first treatment of choice for functional daytime urinary incontinence (DUI) in children. Alarm therapy can be a part of urotherapy as it provides the child adequate feedback on wetting accidents. Current alarm systems notify either at a set interval or give a notification when wetting has already occurred to prompt the child to go to the toilet. These alarms do not teach the child the interpretation of the bladder sensation preceding wetting accidents. A new wearable bladder sensor, the SENS-U, recently became available. This is a relative small, wireless ultrasonic sensor, which continuously monitors bladder filling. The SENS-U is able to provide an alarm at the exact moment voiding is warranted. It facilitates the child to learn the sensation of bladder filling preceding voiding in an easier way, increasing the learning curve throughout treatment. Its additional effect in urotherapy on continence and cost-effectiveness is to be determined. METHODS/DESIGN: This is a multi-center clinical superiority parallel-group randomized controlled trial including a total of 480 children. Participants between 6 and 16 years of age with functional DUI in which urotherapy is offered as the next treatment of choice are eligible. Four centers, two academic hospitals, and two general care (peripheral) centers are participating. Participants will be randomized at a 1:1:1 ratio into three groups: urotherapy (care as usual), urotherapy with the SENS-U added for 3 consecutive weeks throughout the training, or urotherapy with a SHAM device for 3 weeks. The primary outcome is number of wetting accidents per week after 3 months of training, compared between the SENS-U and the SHAM device. The magnitude of the placebo effect will be assessed by comparing the results of the SHAM group versus the control (care as usual) group. DISCUSSION: To our knowledge, this is the first trial studying not only the effect but also the cost-effectiveness of alarm interventions as commonly added in urotherapy. TRIAL REGISTRATION: ISRCTN44345202 . Registered on March 2022.

Comparison of preputioplasty and circumcision in distal hypospadias correction: long-term follow-up.

OBJECTIVE: A normal penile cosmesis is an important goal in distal hypospadias repair. Depending on cultural standards, repairs are combined with a preputioplasty or circumcision to attain a 'normal' penile appearance. Although short-term complication rates of preputioplasty are available, data on long-term outcomes are scarce. Therefore, this study assessed long-term functional and cosmetic outcomes of distal hypospadias repair with either a preputioplasty or a circumcision. PATIENTS AND METHODS: Eligible for inclusion were patients with distal hypospadias operated in childhood between 1987 and 1993. Complications and reasons for secondary circumcision were extracted from the medical charts. Participants completed a questionnaire including the International Index of Erectile Function (IIEF-15), the International Prostate Symptom score (IPSS), and additional non-validated questions. Penile cosmesis was judged with the Penile Perception Score (PPS), stretched penile length was measured, and uroflowmetry was performed. RESULTS: Of the 86 eligible and traceable patients, 40 (47%) participated; of them, 27 had a preputioplasty and 13 a circumcision. Six patients underwent a secondary circumcision due to a preputial defect (n = 2), unsatisfactory cosmetic result (n = 2), religious reason (n = 1), or phimosis (n = 1). Complication rates were similar in both the groups. Long-term outcomes in the preputioplasty and circumcision group were comparable regarding cosmetic, sexual, and micturition outcomes. CONCLUSIONS: Distal hypospadias correction combined with preputioplasty had complication rates similar to those of hypospadias repair with circumcision. In these patients, preputioplasty had a failure rate of 22%. In both the groups, long-term outcomes of urinary function, sexual function, and cosmesis were good.

The multilayered structure of the human corpus spongiosum.

PURPOSE: Urethral reconstruction is performed in patients with urethral strictures or for correction of congenital disorders. In the case of shortage of tissue, engineered tissue may enhance urethral reconstruction. As the corpus spongiosum (CS) is important in supporting the function of the urethra, tissue engineering of the urethra should be combined with reconstruction of a CS. For that purpose, detailed knowledge of the composition of the CS, more specifically its extracellular matrix (ECM) and vascularization is needed for scaffold design. The objective of this study is to analyze the microarchitecture of the CS through (immuno) histology and scanning electron microscopy (SEM). METHODS: The CS including the urethra of patients undergoing male-to-female genital confirming surgery was harvested. This CS was fixed and processed for either (immuno) histology or for SEM. RESULTS: Four layers could be distinguished in the CS; first a transition zone from urethra epithelium to a collagen rich layer, which was highly vascularized, followed by a second, elastin rich layer. The third layer was formed by veins, arteries and vascular spaces and the last layer showed the transition from this vascular rich region to the collagen rich tunica albuginea. In this layer collagen bundles intertwined with elastic fibres. In the CS different components of the ECM were visible and distinguishable. CONCLUSION: This study provides novel and detailed information on the microarchitecture of the CS and the distribution of vascularization, which is important for scaffold design in tissue engineering.

Testosterone prior to hypospadias repair: Postoperative complication rates and long-term cosmetic results, penile length and body height.

INTRODUCTION: The use of hormonal therapy was first described in 1971 before hypospadias surgery, and it has been debated ever since. The long-term outcomes after puberty of patients treated with pre-operative testosterone in childhood are lacking. OBJECTIVES: Possible long-term effects of testosterone are often asked about in daily practice. The current study investigated the long-term outcomes regarding height, penile length and penile cosmesis in adult men after hypospadias surgery in childhood with and without pre-operative testosterone. METHODS: Adult men (n = 121) who underwent primary hypospadias repair in childhood were included. Pre-operative penile appearance, judged by a paediatric urologist, determined the use of pre-operative testosterone. Data on hypospadias characteristics, healing complications, surgical repair, and testosterone use were collected retrospectively. At adult age, stretched penile length and body height were measured, and penile cosmesis was evaluated using the Pediatric Penile Perception Score (PPPS). RESULTS: Postoperative complication rates in patients (n = 121) with and without testosterone were similar (50% vs. 43%; P = 0.54). Sixty adult patients (50%) with a median age of 19.8 years and follow-up time of 18.3 years were examined at the outpatient clinic at adult age. Of this group, testosterone was applied in 12/43 patients with distal, 3/6 patients with midshaft, and 9/11 patients with proximal hypospadias. Adult stretched penile length (12.0 cm vs. 12.4 cm; P = 0.47) and adult height (180.1 cm vs. 179.0 cm P = 0.65) showed no difference between patients with and without testosterone treatment. Penile cosmesis was (very) satisfactory in all PPPS domains, and showed no difference between the testosterone group and the non-testosterone group. Univariate and multivariate analysis was conducted to determine if the hypospadias type or pre-operative testosterone therapy had more influence on the long-term outcomes. None of the long-term outcomes were significantly associated with pre-operative testosterone therapy on multivariate analysis. DISCUSSION: This was the first study reporting long-term outcomes of hypospadias patients after puberty who received pre-operative hormonal therapy. Validated instruments were used as much as possible. Shortcomings of this study were the 50% response rate, the retrospective design, and the lack of objective inclusion criteria reported to indicate pre-operative testosterone therapy. CONCLUSION: This study suggested that the long-term results of patients receiving pre-operative testosterone treatment, who often had more challenging hypospadias, were similar to those who did not. However, a randomised controlled study is needed to confirm these results.

The management of adolescents with neurogenic urinary tract and bowel dysfunction.

Most children with neurogenic bladder dysfunction arrive into adolescence with reasonably managed lower urinary tract function only to experience bladder and kidney function deterioration after puberty. The aim of this article is to identify issues that contribute to adverse changes in bladder and renal function during adolescence and to highlight strategies to preserve urinary tract integrity, social continence, patient autonomy, and independence. Surveillance of bladder function requires patient attendance at review appointments and compliance with treatment plans. While encouraging independence and treatment compliance the clinician also needs to consider altered mental concentrating ability and fine motor skills of these patients. A keen eye for imminent loss of patient compliance to treatment protocol should be the mainstay of each encounter during puberty and adolescence. Annual surveillance of adolescent neurogenic bladder patients facilitates early identification of risk factors for urinary tract deterioration. Investigations include renal and bladder ultrasonography, urodynamic study when indicated, substantiated by videocystometry when anatomical status dictates. Serum creatinine should be measured and renal scintigraphy performed when upper urinary tract dilation, renal scarring, or atrophy are suspected. Optimal management of adolescents with neurologic disease of the urinary tract included strategies to reduce elevated detrusor pressure, maintain bladder compliance, and maximize dryness. Antimuscarinic medications, botulinum toxin A, and surgical procedures are enhanced by bowel management regimens and regular nurse or urotherapist patient contact. Caring for the patient as a whole requires discussion of sexuality, fertility status, and behaviors that increase the risk of progressive urinary tract damage.

Functional, cosmetic and psychosexual results in adult men who underwent hypospadias correction in childhood.

OBJECTIVE: Long-term results of hypospadias repair are scarce. Previous reviews mostly described mid-term results making extrapolation to long-term results difficult. This systematic review on long-term results in postpubertal men after hypospadias repair in childhood, aims to inform urologists and parents of a newborn boy with hypospadias about future expectations. METHODS AND MATERIALS: The Pubmed/Medline and Embase databases were searched until February 2010. Inclusion criteria stated that patients with hypospadias were operated before the age of 6 years and were older than 14 years at follow up. Results were pooled and analyzed using SPSS 16.0. Data on proximal hypospadias patients and controls are described separately. RESULTS: Twenty eligible studies investigating micturition, cosmesis and psychosexual functioning were found. Hypospadias patients report more urinary symptoms and have a lower Qmax than controls. Patients are less satisfied with penile appearance compared to controls. Objectively assessed cosmetic results are good. Sexually, patients are as active as controls, but are less satisfied. Patients less often have an intimate relationships compared to controls. CONCLUSION: Study outcomes were heterogeneous due to operation techniques and a lack of validated questionnaires and control groups. Long-term results of hypospadias patients should be measured in a prospective design using validated measurement tools.

Assessment of non-neurogenic incontinence and lower urinary tract symptoms in adolescents and young adults.

AIMS: The aim of this article is to provide insight to clinicians who principally treat adults, about non-neurogenic lower urinary tract symptoms (LUTS) either pre-dating or presenting in adolescence. Assessment fundamentals, diagnostic classification, and rationale behind the process of care are discussed. METHODS: Standardized terms are used to describe the current classification of symptoms of LUT dysfunction in young adults. The etiology and symptomatology of continuous and organic incontinence, along with the intermittent presentations of incontinence, nocturnal enuresis, and bowel dysfunction are presented. Minimally acceptable assessment processes are defined. Indications for the inclusion of urodynamic investigations are presented. Throughout the review specific needs of adolescents, as they apply to clinical management of LUTS, are highlighted. RESULTS: Puberty and growth are likely to challenge compensatory mechanisms for a safe urinary system in young adults with organic/structural/developmental LUT disorders. The priority of care is to screen for and detect precursor signs of renal deterioration. In adolescents with non-neurogenic bladder dysfunction a clear diagnosis and identification of both incomplete bladder emptying and high detrusor pressure will minimize permanent changes to both the upper and lower urinary tracts. CONCLUSIONS: The assessment of adolescents with LUTS requires time, thoughtful enquiry, and communication. Dysfunction pre-dating young adulthood commonly inhibits autonomy, recreational and social activities thus impacting on the adolescent's self-esteem and adherence to treatment regimes.

Rare cause of ureteral stenosis more than 10 years after kidney transplantation.

Late renal graft failure is in most cases due to a chronic allograft nephropathy. In this report, we present a case in which a surgical complication led to ureteral stenosis more than 10 years after transplantation. The patient developed slowly deteriorating renal function and ultimately progressive hydronephrosis. At surgical exploration, the ureter was found to perforate the wall of the small bowel before entering the bladder. We successfully performed ureter reimplantation to restore the outflow of the kidney.