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Background: Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamicpituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism. Methods:The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects. Results:We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported.

Alpha-blockers as medical expulsive therapy for ureteral stones (Review)

Objective To determine the incidence of penile intraepithelial neoplasia in the Netherlands using a nationwide histopathology registry and to discuss the nomenclature of premalignant penile lesions. Methods Data from patients in the Netherlands diagnosed with a premalignant penile lesion between January 1998 and December 2007 were collected from the nationwide histopathology registry (PALGA); this database covers all pathology reports of inhabitants in the Netherlands. The premalignant lesions included were erythroplasia of Queyrat; Bowen's disease; bowenoid papulosis; mild, moderate and severe dysplasia; and carcinoma in situ of the penis. The terminology used in the pathological reports was translated to penile intraepithelial neoplasia. The grading was made analogous to that of vulvar premalignant lesions. Results The PALGA database enrolled 380 patients with premalignant penile lesions. Severe premalignant lesions, penile intraepithelial neoplasia III, were found in 254 patients (67%), penile intraepithelial neoplasia II in 84 (22%) and penile intraepithelial neoplasia I in 42 patients (11%). Most lesions were located on the prepuce (45%), followed by glans (38%) and shaft (3%). The median age of patients with penile intraepithelial neoplasia was 58 years. Progression to malignant disease occurred (2% for penile intraepithelial neoplasia I vs 7% for penile intraepithelial neoplasia III) in 26 patients. Conclusions Penile intraepithelial neoplasia is a rarely diagnosed condition. Because of the wide variation of terms used for premalignant intraepithelial neoplasia of the penis, we recommend restricting this nomenclature to penile intraepithelial neoplasia.

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We have developed a protocol for the identification of aberrant chromosome behavior during human male meiosis up to metaphase of the secondary spermatocyte. Histological evaluation by the Johnsen score of a testicular biopsy was combined with immunofluorescence of first meiotic prophase spermatocytes, using antibodies against synaptonemal complex protein 3 (SYCP3) and the product of the ataxia telangiectasia and rad3-related gene (ATR). This combination enables accurate meiotic prophase substaging and the identification of pachytene spermatocytes with asynapsis. Furthermore, we also investigated the competence of late pachytene primary spermatocytes to complete the first meiotic division up to metaphase and of secondary spermatocytes to transform into metaphase by an in vitro challenge with okadaic acid (OA). We tested this protocol on five males with normal Johnsen scores that presented with obstructive azoospermia, five males with low Johnsen scores and non-obstructive azoospermia and six vasectomized control males of proven fertility and normal Johnsen scores. In all azoospermics, the profiling of meiotic prophase stages by immunofluorescence increases the resolving power of the Johnsen score. In both obstructive and non-obstructive azoospermic patients, relatively more leptotene meiotic prophase stages were counted compared to the controls. In non-obstructive azoospermics, a marked heterogeneity in spermatogenesis was found, after combining the results of all three approaches, pointing at functional mosaicism of the germinal epithelium. Asynaptic pachytene spermatocytes were rarely encountered. Also, when first meiotic metaphase could be induced by OA, chiasma counts were normal. In none of the non-obstructive azoospermic males did the pattern of spermatogenesis resemble that of knock-out mouse azoospermics. We conclude that this combined histological and cytological approach enables a detailed phenotypic classification of infertile males, at a level comparable to that applied for male-sterile knock-out mice with a meiotic defect. This may facilitate the identification of candidate genes for human male infertility.

In these patients, in terms of patency and patency duration, open surgery was superior to endourology. Nevertheless, endourological treatments offer a safe and less-invasive alternative to delay or avoid open surgery, especially in patients who are unfit for open surgery.

ObjectiveTo assess the performance of hybrid (HIR) and model-based iterative reconstruction (MIR) in patients with urolithiasis at reduced-dose computed tomography (CT).MethodsTwenty patients scheduled for unenhanced abdominal CT for follow-up of urolithiasis were prospectively included. Routine dose acquisition was followed by three low-dose acquisitions at 40%, 60% and 80% reduced doses. All images were reconstructed with filtered back projection (FBP), HIR and MIR. Urolithiasis detection rates, gall bladder, appendix and rectosigmoid evaluation and overall subjective image quality were evaluated by two observers.Results74 stones were present in 17 patients. Half the stones were not detected on FBP at the lowest dose level, but this improved with MIR to a sensitivity of 100%. HIR resulted in a slight decrease in sensitivity at the lowest dose to 72%, but outperformed FBP. Evaluation of other structures with HIR at 40% and with MIR at 60% dose reductions was comparable to FBP at routine dose, but 80% dose reduction resulted in non-evaluable images.ConclusionsCT radiation dose for urolithiasis detection can be safely reduced by 40 (HIR)–60 (MIR) % without affecting assessment of urolithiasis, possible extra-urinary tract pathology or overall image quality.Key Points • Iterative reconstruction can be used to substantially lower the radiation dose. • This allows for radiation reduction without affecting sensitivity of stone detection. • Possible extra-urinary tract pathology evaluation is feasible at 40–60% reduced dose. Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-017-4929-2) contains supplementary material, which is available to authorized users.