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Male hypogonadism is a congenital or acquired disorder that exerts a negative influence on various organ functions and can massively impair the quality of life through the relative or absolute deficiency of testosterone. A variety of preparations are available for substitution treatment, which differ in administration form and intake interval. For the execution of testosterone treatment various guidelines exist with clear and practical instructions on the indications, contraindications, treatment procedure and monitoring. Of particular importance are cardiovascular aspects and diseases of the prostate gland, which underlines the central position of the urologist in the treatment.Beim männlichen Hypogonadismus handelt es sich um eine kongenitale oder erworbene Erkrankung, die durch den vorliegenden relativen oder absoluten Testosteronmangel einen negativen Einfluss auf verschiedene Organfunktionen ausübt und die Lebensqualität massiv beeinträchtigen kann. Zur Substitutionsbehandlung stehen verschiedene Präparate zur Verfügung, welche sich in der Darreichungsform und den Einnahmeintervallen unterscheiden. Zur Durchführung der Testosterontherapie existieren mehrere Leitlinien mit klaren und praktischen Handlungsanweisungen zu Indikationsstellung, Kontraindikationen, Therapiedurchführung und -monitoring. Hierbei sind insbesondere kardiovaskuläre Aspekte und Erkrankungen der Prostata von Bedeutung, was die zentrale Stellung des Urologen in der Behandlung verdeutlicht.

Sexual health is becoming increasingly important for many HIV-positive men undergoing highly effective antiretroviral therapy (ART) but remains frequently unaddressed in routine clinical consultation.To comprehensively evaluate sexual health in male patients with HIV on stable ART over a 12-month period.The prospectively registered cohort study comprising 87 HIV-positive men on stable ART (median age: 43 years) was conducted between 2011 and 2015 at a university hospital. Patients were enrolled from the outpatient infectious disease unit and underwent an extensive andrological workup to assess parameters of sexual health (questionnaires, sex hormones, ultrasound, 2-glass urine test including semen analysis with microbiological and viral diagnostics). The study period per patient lasted 12 months.The primary endpoint was the impact of chronic HIV infection on sexual health.Although, on average, sexual health was fine at baseline, 56% of the patients reported erectile dysfunction, 28% experienced reduced libido, 5% had hypogonadism, 36% showed at least 1 atrophic testicle with a volume of10 ml, 8% suffered bacterial sexually transmitted infections, 35% had seminal inflammation, and up to 47% showed reduced sperm quality. Sexual satisfaction was linked to mental health (12-Item Short Form Health Survey questionnaire) and International Index of Erectile Function scores. During the study period, the collected parameters on sexual health were generally stable. However, 35% of patients had new sex partners (median: 5 partners), 7% had fathered a child or were planning procreation, 47% reported changed libido, 17% suffered bacterial sexually transmitted infections in the urogenital tract, 16% revealed a positive HIV viral load in blood, 11% had a positive HIV viral load in semen, and 28% were treated for andrological disorders.Sexual ill-health exists in about one third of patients. This manifests itself in sexual dysfunction, sexually transmitted infections, urogenital tract inflammation, and abnormal sperm parameters, all of which require adequate counseling and therapy.The strength of this study is its comprehensive analysis of male sexual health over a 12-month period of stable ART treatment. Limitations are a heterogeneous patient cohort and a rather small percentage of patients with a positive HIV viral load in blood or semen, which prevented multivariate risk analysis.Our study provides evidence that sexual health should be actively taken into account in the routine consultation by infectious disease specialists, and an interdisciplinary approach is desirable in the case of symptoms or signs of sexual ill-health. Pilatz A, Maresch CC, Discher T, et al. Sexual Health in HIV-Positive Men Under Stable Antiretroviral Therapy During a 12-Month Period. J Sex Med 2021;18:284-294.

Although the evolutionary history of the X chromosome indicates its specialization in male fitness, its role in spermatogenesis has largely been unexplored. Currently only three X chromosome genes are considered of moderate-definitive diagnostic value. We aimed to provide a comprehensive analysis of all X chromosome-linked protein-coding genes in 2,354 azoospermic/cryptozoospermic men from four independent cohorts. Genomic data were analyzed and compared with data in normozoospermic control individuals and gnomAD. While updating the clinical significance of known genes, we propose 21 recurrently mutated genes strongly associated with and 34 moderately associated with azoospermia/cryptozoospermia not previously linked to male infertility (novel). The most frequently affected prioritized gene, RBBP7, was found mutated in ten men across all cohorts, and our functional studies in Drosophila support its role in germ stem cell maintenance. Collectively, our study represents a significant step towards the definition of the missing genetic etiology in idiopathic severe spermatogenic failure and significantly reduces the knowledge gap of X-linked genetic causes of azoospermia/cryptozoospermia contributing to the development of future diagnostic gene panels., This work was funded by Spanish Ministry of Health Instituto Carlos III-FIS (grant numbers PI17/01822 and PI20/01562) and the Fanconi Research Fund awarded to C.K. and A.R.-E.; the German Research Foundation Clinical Research Unit “Male Germ Cells” (DFG CRU326), grants to F.T. and C.F.; the National Institutes of Health (R01HD078641), awarded to D.F.C., L.N., and K.I.A.; the Netherlands Organisation for Scientific Research (918-15-667) as well as an Investigator Award in Science from the Wellcome Trust (209451) to J.A.V.; and the MICINN (BFU2015-65082-P and PGC2018-094538-B-I00), the Generalitat de Catalunya (SGR2009-1023 and SGR2014-204), and the European Community FEDER program to F.A.

International audience; Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as "non-self" by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is "outside" the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.

Objectives: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. Materials and Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. Results: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. Conclusion: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Introduction: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic’s background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. Results: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. Conclusion: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

The objective of this study was to assess whether CCDS might improve the outcome of testicular sperm retrieval in patients with azoospermia. Furthermore, we evaluated potential sonographic alterations of the testis before and after trifocal and Micro-TESE. 78 patients were enrolled prospectively: 24 with obstructive azoospermia (OA) and 54 with non-obstructive azoospermia (NOA). 31 of 54 patients in the NOA group had negative surgical sperm retrieval. Testicular volume, hormonal parameters and sonographical findings were compared before and after TESE. The spermatogenetic score was determined for all retrieval sites. CCDS was performed at the upper, middle and lower segment of the testis. Ultrasound parameters and peak systolic velocity (PSV) were measured pre- and post-operatively. Testicular volume and epididymal head size were significantly increased in OA patients compared to NOA patients. Ultrasound parameters were comparable between NOA patients with and without successful sperm retrieval. A higher intratesticular PSV was significantly correlated with a better spermatogenic score in the corresponding sonographic position. However, after adjustment for other clinical confounders, PSV does not show a significant influence on the spermatogenic score. Testicular volume decreased significantly in all patients post-operatively after 6 weeks (p

Considering infection/inflammation to be an important risk factor in male infertility, the aim of this study was to make a comprehensive evaluation of the prevalence of urogenital tract infection/inflammation and its potential impact on sperm retrieval in azoospermic patients. In this prospective study, 71 patients with azoospermia were subjected to an extensive andrological workup including comprehensive microbiological diagnostics (2‐glass test, semen, testicular swab and testicular tissue analysis) and testicular biopsy/testicular sperm extraction (TESE). Medical history suggested urogenital tract infection/inflammation in 7% of patients, 11% harboured STIs, 14% showed significant bacteriospermia, 15% had seminal inflammation, 17% fulfilled the MAGI definition, and 27% had relevant pathogens. At the testicular level, 1 patient had a swab positive for bacteria, no viruses were detected, tissue specimens never indicated pathogens, whereas histopathology revealed focal immune cell infiltrates in 23% of samples. Testicular sperm retrieval rate was 100% in obstructive and 46% in nonobstructive azoospermia. None of the infection/inflammation‐related variables was associated with the success of sperm retrieval or inflammatory lesions in the testis. The high prevalence of urogenital infection/inflammation among azoospermic men underpins their role as significant aetiologic factors in male infertility. However, this observation does not refer to the chances of sperm retrieval at the time of surgery/TESE.

Context Empiric use of medical and nutritional supplements to improve semen parameters and pregnancy rates in couples with idiopathic infertility has reached global proportions, although the evidence base for their use in this setting is controversial. Objective We systematically reviewed evidence comparing the benefits of nutritional and medical therapy on pregnancy rates and semen parameters in men with idiopathic infertility. Evidence acquisition A literature search was performed using MEDLINE, Embase, LILACS, and the Cochrane Library (searched from January 1, 1990 to September 19, 2017). using the methods detailed in the Cochrane Handbook. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Evidence synthesis The literature search identified 5663 citations, and after screening of abstracts and full texts, 61 studies (59 randomised controlled trials and two nonrandomised comparative studies) were included. Pooled results demonstrated that pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein all resulted in improvements in semen parameters. Individual studies identified several other medical and nutritional therapies that improved semen parameters, but data were limited to individual studies with inherent methodological flaws. There were limited data available on live birth and pregnancy rates for all interventions. The GRADE certainty of evidence for all outcomes was very low mainly owing to methodological flaws and inconsistencies in study design. Some outcomes were also downgraded owing to imprecision of results. Conclusions There is some evidence that empiric medical and nutritional supplements may improve semen parameters. There is very limited evidence that empiric therapy leads to better live birth rates, spontaneous pregnancy, or pregnancy following assisted-reproductive techniques. However, the findings should be interpreted with caution as there were some methodological flaws, as a number of studies were judged to be either at high or unclear risk of bias for many domains. Patient summary This review identified several medical and nutritional treatments, such as pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein, that appear to improve semen parameters. However, there are limited data suggesting improvements in pregnancy and live birth rates. The lack of evidence can be attributed to methodological flaws in studies and the low number of pregnancies reported.

OBJECTIVES: To investigate semen quality in HIV patients under stable antiretroviral therapy (ART) compared with WHO 2010 reference values and on the sperm proteome level. DESIGN: Between 2011 and 2013, we prospectively enrolled 116 HIV-positive men without hepatitis B or C co-infections from our outpatient department for infectious diseases. METHODS: Patients received a comprehensive andrological work-up. Complete semen analysis was performed according to WHO 2010 recommendations, with each semen variable of the study population being compared with the WHO reference group (n~2000). Correlation analysis was done to investigate the influence of HIV surrogate parameters on semen quality. Two-dimensional gel electrophoresis and subsequent protein identification was performed to determine any differences in the sperm protein composition of the 15 HIV-positive patients and that of 15 age-matched healthy men. RESULTS: Median values of all assessed semen parameters were within a normal range. However, for each semen variable, about 25% of patients had values below the fifth percentile of the WHO 2010 reference group. Disease-related parameters (CD4þ cell count, viral load, CDC stage, duration of disease, duration of ART, number and type of antiretroviral drugs) were not significantly correlated with any sperm parameter. Sperm proteome analysis identified 14 downregulated proteins associated with sperm motility and fertility. CONCLUSION: This is the first study that compares all standard semen parameters in HIV positive patients under ART to WHO 2010 reference values. It provides evidence of impaired conventional semen parameters and altered sperm protein composition. Finally, HIV surrogate parameters are not suitable for predicting semen quality.

Summary As commonly used self-reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self-rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease-related risk to develop hypogonadism. Two hundred and eighteen patients aged 19–71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)-12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, oestradiol and sex hormone-binding globulin were determined and free testosterone was calculated. Cronbach's α for the scale was 0.896, split-half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman–Brown coefficient was 0.767, and Guttman split-half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P

The prostatitis syndrome is classified into bacterial prostatitis (acute and chronic), chronic pelvic pain syndrome and asymptomatic prostatitis. The aim of this report is to review current management standards for bacterial prostatitis.A research was performed on literature dealing with acute and chronic bacterial prostatitis.There is a consensus on diagnostic management of bacterial prostatitis comprising microbiological sampling of midstream urine in acute bacterial prostatitis and performance of a bacterial localisation test in chronic bacterial prostatitis. Approximately 10 % of acute bacterial prostatitis cases eventually develop into chronic bacterial prostatitis and further 10 % into chronic pelvic pain syndrome. Bacterial isolates causing acute bacterial prostatitis are highly virulent strains comprising an array of different virulence factors. Presumably, the additional ability of isolates to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis. Therapy for infectious prostatitis is standardised with antibiotics as the primary agents, empirically administered in acute prostatitis and after susceptibility testing in chronic bacterial prostatitis. Fluoroquinolones exhibit more favourable pharmacological properties; therefore, fluoroquinolones have been recommended as first-line agents in the treatment for chronic bacterial prostatitis. Antibiotic resistance to fluoroquinolones, however, is increasing and is posing significant clinical problems. Further studies on alternative antibiotics active within the prostate are therefore needed both for prophylaxis in transrectal prostate biopsy, for example, and for therapy of chronic bacterial prostatitis.Bacterial prostatitis has developed into well-managed entities with increasing antimicrobial resistance being the most severe drawback of yielding therapeutic success.

The most common pathologies of the seminal tract are persistent hematospermia, seminal vesicle stones, and seminal duct obstruction. Endoscopic diagnostic work-up of the seminal tract is impeded by complex anatomy and lack of technical equipment. To date, there is no standardized endoscopic approach. The purpose of this study was to investigate the applicability and feasibility of a flexible microoptical device for atraumatic endoscopy of the seminal tract in a male human cadaver.The transurethral endoscopic examination was performed on a male cadaver. No premortal interventions or diseases of the genitourinary tract had been reported. The seminal orifice was identified via cystoscopy and accessed by the Seldinger technique using a hydrophilic guidewire and ureteral catheter. Retrograde endoscopic inspection of the distal seminal tract was performed using a miniaturized flexible endoscope. An antegrade endoscopic inspection of the seminal tract was carried out via high scrotal access to the vas deferens.Structures of the seminal tract, such as the ejaculatory duct, seminal vesicles, and distal portion of the ductus deferentes, were visualized using the miniaturized endoscope. Image quality allowed identification of anatomical structures and characterization of tissue properties. The technical limitations we observed involved the system's maneuverability.Initial results of this novel endoscopic approach to the seminal tract using a flexible microoptical system are encouraging. However, considerable anatomical limitations of the targeted organs necessitate further refinements of the technical equipment. This approach might improve diagnostics and treatment of genitourinary diseases. Future surgical techniques may include intraseminal laser therapy or endoocclusion to monitor fertility in men.

The association between chronic inflammatory/infectious diseases of the male reproductive tract and the presence of antisperm antibodies (ASA) in semen is still controversial. We compared the results of the mixed agglutinin reaction (MAR) test and immunobead test for detecting ASA type IgG and IgA in 133 patients attending our special outpatient department for andrological infections and evaluated the differences in the detection rate of ASA. Patients were divided into three groups: a study group that included 79 patients with symptomatic nonacute inflammatory/infectious diseases of the seminal tract, a control group (n = 44) and a third group of men with a history of successful vasectomy reversal (n = 10). The two tests correlated in a statistically significant manner for the detection of IgG and IgA in all groups. The overall positive detection rate of clinical significant levels of IgG and IgA was 2.5% and 1.3% (respectively) in the patients with inflammation/infection of the seminal tract. No statistical significant difference in the detection rate of ASA levels between the inflammatory/infectious group and the controls was detected. The results of the MAR test and immunobead test have a statistical significant correlation and their results provide evidence that there is no association between inflammatory/infectious diseases of the male reproductive tract and the presence of ASA in semen.

Objectives The development of fibrotic diseases is associated with alterations in the transforming growth factor β (TGF-β) pathway. We have investigated the expression and activity of Smad transcription factors of the TGF-β pathway in primary tunical fibroblasts derived from patients with Peyronie's disease and from controls. Methods Primary fibroblasts were established from biopsies obtained from plaques of 16 patients with Peyronie's disease or the tunica albuginea of 8 control patients. The expression and activity of Smad transcription factors in control and TGF-β–stimulated primary fibroblasts were investigated at the RNA and protein level by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence. Results RNA expression levels of Smad3 and Smad4 were significantly increased in fibroblasts from patients with Peyronie's disease. When stimulated with TGF-β1, fibroblasts showed rapid nuclear translocation of Smad2/3, as soon as 15min after stimulation. This effect was more pronounced and exhibited an earlier onset in fibroblasts from patients with Peyronie's disease, compared with controls. In addition, an increased nuclear retention time of Smad4 was observed in fibroblasts from patients with Peyronie's disease. Conclusions The expression and activity of Smad transcription factors of the TGF-β pathway is increased in fibroblasts of patients with Peyronie's disease. Alterations in the TGF-β pathway seem to be a pathogenetic factor in the development of Peyronie's disease.

Background Infections of the genital tract are considered common causes of male fertility disorders, with a prevalence of 6-10%. Most of the affected men are asymptomatic. The diagnostic evaluation is based mainly on laboratory testing. Inconsistent diagnostic criteria have been applied to date, and this may explain the controversial debate about the role of infection and inflammation in the genital tract as a cause of infertility. The risk of an irreversible fertility disorder should not be underestimated. Methods This review is based on pertinent publications retrieved by a selective literature search in PubMed, including guidelines from Germany and abroad and systematic review articles. Results The main causes of inflammatory disease of the male genital tract are ascending sexually transmitted infections (STIs) and uropathogens. Chronic prostatitis has no more than a limited influence on ejaculate variables. By contrast, approximately 10% of men who have had acute epididymitis develop persistent azoospermia thereafter, and 30% have oligozoospermia. Obstruction of the excurrent ducts can ensue, as can post-infectious disturbances of spermatogenesis. The differential diagnostic evaluation includes the determination of testicular volumes, hormone concentrations, and ejaculate variables. Epidemiological data are lacking with regard to infertility after primary orchitis of infectious origin; however, up to 25% of testicular biopsies obtained from infertile men reveal focal inflammatory reactions. Multiple studies have suggested a deleterious effect of leukocytes and inflammatory mediators on sperm para - meters. On the other hand, the clinical significance of bacteriospermia remains unclear. Conclusion Any suspicion of an infectious or inflammatory disease in the male genital tract should prompt a systematic diagnostic evaluation and appropriate treatment. For patients with obstructive azoospermia, the etiology and site of the obstruction determine the surgical approach to be taken. In the near future, the elucidation of underlying pathophysiological mechanisms and the identification of suitable biomarkers may enable new strategies for conservative treatment.

Chronic inflammatory disease and acute infection are well known to inhibit gonadal steroidogenesis. Previous studies have demonstrated that immune activation in response to lipopolysaccharide (LPS) results in reductions in serum testosterone, and this is a direct effect on the Leydig cell. We hypothesize that during the early onset of LPS endotoxemia in vivo, testicular macrophages produce reactive oxygen species (ROS) leading to perturbation of Leydig cell mitochondria and an inhibition in steroidogenesis. To investigate the mechanism of LPS inhibition of Leydig cell steroidogenesis, alterations in mitochondria and markers of oxi-dative stress were assessed in vivo and in Leydig cell pri- mary culture. After a single injection of mice with LPS, serum testosterone was significantly decreased within 2 h. LPS injection of mice resulted in significant reductions in steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid dehydogenase-Delta4-Delta5 isomerase (3beta-HSD) proteins. LPS significantly increased lipid peroxidation of Leydig cell membranes, indicating that LPS results in oxidative damage in vivo. Mitochondria in Leydig cells isolated from LPS-injected mice were disrupted and showed a marked reduction in the mitochondrial membrane potential (DeltaPsim). Similar to the effects of LPS, treatment of Leydig cells with hydrogen peroxide acutely inhibited steroidogenesis, reduced StAR and 3beta-HSD protein levels, and disrupted DeltaPsim. These results suggest that LPS acutely inhibits Leydig cell function by ROS-mediated disruption of Leydig cell mitochondria. Taken together, these results demonstrate the necessity of having respiring mitochondria with an intact DeltaPsim to facilitate StAR function and Leydig cell steroidogenesis. The acute effects of LPS demonstrate how sensitive Leydig cell mitochondrial steroidogenesis is to inflammation-induced oxidative stress.

We report a case of giant multilocular cystadenoma of the prostate in a 43-year-old man. This is a rare benign entity of the prostate imitating symptoms of benign prostatic hyperplasia and originates from the prostate with extensive spread into the pelvis. Histologically, prostatic glands and cysts lined by cuboid to columnar epithelial cells with basally located nuclei are characteristic. Immunohistochemical staining is positive for prostate-specific antigen in the epithelial cells. Giant multilocular prostatic cystadenoma should be taken into account in the differential diagnosis in any case of a large cystic mass originating from the prostate.

During the last years tremendous changes have occurred in the epidemiologic knowledge and the diagnostic process of the prostatitis syndrome. A new worldwide-accepted classification system has become the gold standard in contemporary literature. The aim of this study was to compare the inflammatory and infectious status of men with prostatitis syndrome with results from our study cohort from 1992. A total of 168 symptomatic men (mean age 43.2 years; range 18-79) attending the Giessen prostatitis outpatient department were included. All men underwent a standard four-glass-test including leucocyte analysis in all specimens. A routine search for Ureaplasma urealyticum and Chlamydia trachomatis was performed. Ejaculate analysis following World Health Organization (WHO) criteria has been performed including the evaluation of increased number of peroxidase-positive leucocytes (PPL). Men were classified according to the National Institutes of Health (NIH) prostatitis classification. The distribution of patients according to NIH criteria is as follows: NIH II (4.2%), NIH IIIA (31.5%), NIH IIIB (50.0%) and urethroprostatitis (14.3%). Chlamydial infection was present in one man (0.6%). Only two men with increased leucocytes in prostatic secretions demonstrated ≥10 6 million ml -1 PPL in semen. As compared with our cohort study 10 years ago, the proportion of the different subtypes of the prostatitis syndrome have remained stable. The aetiological spectrum of chronic bacterial prostatitis has not changed whereas, in contrast, the prevalence of C. trachomatis now is found to be strikingly reduced. Using the WHO cutpoints for leucocytospermia the inclusion of seminal leucocytes to the diagnostic process has not influenced the distribution between inflammatory (type NIH IIIA) and noninflammatory (type NIH IIIB) chronic pelvic pain syndrome.

We report on a case of penile epithelioid sarcoma in a 29-year-old man presenting with a dorsal penile plaque that primarily was misdiagnosed as Peyronie's disease. Although the initial clinical findings of these two different entities appear similar, the consequence for the patient is severe. The only way of differentiating these disorders are histological findings. The principal microscopic characteristics of epithelioid sarcoma are the distinctive nodular arrangement, central degeneration and necrosis of the tumor cells with epithelioid appearance and eosinophilia. Immunohistochemical data (cytokeratin, epithelial membrane antigen, vimentin, CD 34, desmin) confirm the diagnosis. We conclude that in cases with slightest doubts on the diagnosis of Peyronie's disease, especially in younger men suffering from a fast-growing penile induration, a bioptic clarification of the entity should be performed to exclude a high malignant disease that can be only treated as far as it is localized by radical surgery.

This study evaluated the long-term outcome of the Essed-Schroeder procedure for correcting congenital penile curvature using non-absorbable Goretex sutures. The Essed-Schroeder procedure was performed in 35 patients with congenital ventral penile curvature (minimum 30 degrees ). Follow-up included a standardized interview with measurement of angulation. Twenty-three of 35 patients were available for complete long-term follow-up (average 34.3 months). The mean preoperative ventral curvature was 54 degrees. In 17/23 patients, the penis remained straightened. Recurrent curvature (average 23 degrees ) was observed in six of 23 patients. Fifteen of 23 patients complained of penile shortening (average 1.8 cm). Two of 23 patients reported disturbing side effects that were caused by plication nodes. In most cases, the results of penile straightening by the Essed-Schroeder procedure are excellent with a high grade of subjective satisfaction. Regarding the main problem, that is recurrent curvature, there is no decisive advantage of applying Goretex sutures. Discomfort caused by plication nodes can be reduced to a minimum by using a combination of soft Goretex sutures with the 'inverting stitch-technique'.

We evaluated the long-term results of plaque thinning by carbide burs, small transverse incisions and venous grafting for correcting complex penile curvature in patients with Peyronie's disease.A total of 13 patients with Peyronie's disease and complex penile curvature received plaque thinning by carbide burs equipped with a fraise, small plaque incision and venous grafting. All patients were available for long-term followup at a mean of 29 months. Preoperatively the mean dorsal curvature angle was 73 degrees with an additional malrotation in 4 patients. Followup consisted of a standardized interview and 3-dimensional photo documentation during erection.Although penile straightening was achieved intraoperatively, dorsal curvature (mean 35 degrees) recurred in 8 men, of whom 3 noticed this deterioration after a longer period. Penile shortening (mean 3.3 cm.) occurred in 7 patients, and decreased rigidity during intercourse occurred in 4.Hypothetically, a combined technique of thinning, incision and grafting seems to be an ideal surgical approach for correction of complex penile curvatures in Peyronie's disease without plaque excision. Although the penis had been completely straightened intraoperatively, severe dorsal curvatures recurred and significant penile shortening became obvious in more than half of the patients. Manipulation of the plaque may be associated with activation of the disease, with all of the risks of recurrence and deterioration. Due to the poor results of the thinning procedures, we stopped using this surgical approach and now prefer a combination of small incisions and grafting only.

Chronic pelvic pain syndromes, including prostatitis, remain a difficult clinical entity in terms of diagnosis and treatment to both urologists and patients. This review attempts to highlight the most recent developments and advances in the field of chronic pelvic pain syndromes in terms of prevalence, aetiology, pathogenesis, diagnosis, and current approaches to treatment.

This study evaluated if the negative influence of Escherichia coli on the motility of human spermatozoa is a consequence of E. coli-induced ultrastructural alterations. Suspensions of spermatozoa were artificially infected with E. coli from a serotyped, pathogenic strain and incubated at 37 degrees C for 6 h. After incubation, spermatozoa were fixed in glutaraldehyde, stained with osmium tetroxide and ruthenium red and embedded in Spurr(R)-resin followed by ultramicrotomy. The sections were analysed subsequently by use of transmission electron microscopy. Uninfected suspensions of spermatozoa in medium and bacterial suspensions served as controls. Negative contrast technique was performed to facilitate visualization of ultrastructural details of the bacterial capsule after experimental exposure to spermatozoa. Electron microscopic evaluation revealed multiple and profound alterations in the ultrastructure of spermatozoa such as membrane defects and cytoplasmic vacuoles exclusively in spermatozoa of infected samples (> 90%). Morphological alterations involved all superficial structures of spermatozoa, in particular the plasma membrane of the mid-piece and neck as well as the inner and outer acrosomal membrane of the acrosome, indicating that morphological defects account for the immobilization of spermatozoa by E. coli. The results suggest that E. coli infection of ejaculates results in immobilization and impaired acrosomal function in human spermatozoa, findings that support the indication for antimicrobial chemotherapy in symptomatic and silent infections that affect the ejaculate.

Inflammatory disease has been established to affect male reproductive function and fertility. Relevant inflammatory diseases include general and chronic infectious diseases as well as localized acute or chronic infections of the male genitourinary tract. Male accessory gland infections account for almost 15% of all cases of male infertility seen in infertility clinics while fertility usually is not a clinical objective among patients with acute systemic infections such as Gram-negative sepsis. Infections of the male accessory glands frequently are associated with increased counts of white blood cells in semen and elevated levels of proinflammatory cytokines in semen and the testis. There is a mounting body of evidence that demonstrates the importance of cytokines and chemokines in the regulation of testicular and glandular function during pathophysiological states as well as under normal physiological conditions when cytokines act as growth and differentiation factors. The purpose of this review is to examine the role of cytokines in the regulation of steroidogenesis and spermatogenesis in the testis under physiological and pathophysiological conditions and considers clinical investigations that help to improve the evaluation and treatment of male infertility.

Context: New data regarding the diagnosis and treatment of male infertility have emerged and led to an update of the European Association of Urology (EAU) guidelines for Male Infertility. Objective: To review the new EAU guidelines for Male Infertility. Evidence acquisition: A comprehensive work-up of the literature obtained from Medline, the Cochrane Central Register of Systematic Reviews, and reference lists in publications and review articles was developed and screened by a group of urologists and andrologists appointed by the EAU Guidelines Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford C Evidence summary: These EAU guidelines are a short comprehensive overview of the updated guidelines of male infertility as recently published by the EAU (http://www.uroweb.org/guidelines/online-guidelines/), and they are also available in the National Guideline Clearinghouse (http://www.guideline.gov/). (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The European Association of Urology presents its guidelines for vasectomy. Vasectomy is highly effective, but problems can arise that are related to insufficient preoperative patient information, the surgical procedure, and postoperative follow-up.These guidelines aim to provide information and recommendations for physicians who perform vasectomies and to promote the provision of adequate information to the patient before the operation to prevent unrealistic expectations and legal procedures.An extensive review of the literature was carried out using Medline, Embase, and the Cochrane Database of Systematic Reviews from 1980 to 2010. The focus was on randomised controlled trials (RCTs) and meta-analyses of RCTs (level 1 evidence) and on well-designed studies without randomisation (level 2 and 3 evidence). A total of 113 unique records were identified for consideration. Non-English language publications were excluded as well as studies published as abstracts only or reports from meetings.The guidelines discuss indications and contraindications for vasectomy, preoperative patient information and counselling, surgical techniques, postoperative care and subsequent semen analysis, and complications and late consequences.Vasectomy is intended to be a permanent form of contraception. There are no absolute contraindications for vasectomy. Relative contraindications may be the absence of children, age30 yr, severe illness, no current relationship, and scrotal pain. Preoperative counselling should include alternative methods of contraception, complication and failure rates, and the need for postoperative semen analysis. Informed consent should be obtained before the operation. Although the use of mucosal cautery and fascial interposition have been shown to reduce early failure compared to simple ligation and excision of a small vas segment, no robust data show that a particular vasectomy technique is superior in terms of prevention of late recanalisation and spontaneous pregnancy after vasectomy. After semen analysis, clearance can be given in case of documented azoospermia and in case of rare nonmotile spermatozoa in the ejaculate at least 3 mo after the procedure.

INTRODUCTION: Studies that compare the impact of different infectious entities of the male reproductive tract (MRT) on the male accessory gland function are controversial. MATERIAL AND METHODS: Semen analyses of 71 patients with proven infections of the MRT were compared with the results of 40 healthy non-infected volunteers. Patients were divided into 3 groups according to their diagnosis: chronic prostatitis NIH type II (n = 38), chronic epididymitis (n = 12), and chronic urethritis (n = 21). RESULTS: The bacteriological analysis revealed 9 different types of microorganisms, considered to be the etiological agents, isolated in different secretions, including: urine, expressed prostatic secretions, semen and urethral smears: E. Coli (n = 20), Klebsiella (n = 2), Proteus spp. (n = 1), Enterococcus (n = 20), Staphylococcus spp. (n = 1), M. tuberculosis (n = 2), N. gonorrhea (n = 8), Chlamydia tr. (n = 16) and, Ureaplasma urealyticum (n = 1). The infection group had significantly (p < 0.05) lower: semen volume, alpha-glucosidase, fructose, and zinc in seminal plasma and, higher pH than the control group. None of these parameters was sufficiently accurate in the ROC analysis to discriminate between infected and non-infected men. CONCLUSION: Proven bacterial infections of the MRT impact negatively on all the accessory gland function parameters evaluated in semen, suggesting impairment of the secretory capacity of the epididymis, seminal vesicles and prostate. These findings were associated with an infectious related significant increase of semen pH. None of the semen parameters evaluated can be suggested as a diagnostic tool for infection.

Background It is debated whether chronic urogenital inflammations and infections may trigger the formation of antisperm antibodies (ASA) in semen. Objective To evaluate the formation of ASA in defined chronic inflammatory and infectious diseases of the male reproductive tract (MRT). Design, setting, and participants Three hundred sixty-five patients retrospectively enrolled in a single center were categorized as having National Institutes of Health (NIH) category II chronic prostatitis ( n =38), NIH category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) ( n =59), NIH category IIIb CP/CPPS ( n =213), chronic epididymitis ( n =34), and chronic urethritis ( n =21). Forty-five age-matched men served as controls. Measurements All subjects underwent microbiologic and cytologic analysis for common bacteria, yeasts, and mycoplasma using the four-glass test. Urine samples, ejaculates, and urethral swabs were analyzed with polymerase chain reaction (PCR) for Chlamydia trachomatis and Neisseria gonorrhea. Semen analysis followed World Health Organization (WHO) standards. ASA in seminal plasma were analyzed using the mixed agglutination reaction (MAR) test. Results and limitations The overall positive detection rate of clinically significant levels (≥50% of spermatozoa coated by ASA) of IgG and IgA antibodies was 1.8% and 0.8%, respectively, in the patient group. No clinically significant levels of ASA were detected in the control group, and no statistically significant difference was observed between controls and patients (IgG, p =1.0; IgA, p =1.0). No difference was found between the different inflammatory and infectious diseases and the control group in the detection rate of ASA, even when the cut-point value was lowered to ≥1% (IgG, p =0.4; IgA, p =0.3). Moreover, in one selected subgroup of patients ( n =26) with persistent increased inflammatory parameters (peroxidase-positive leukocytes [PPL] ≥1×10 6 /ml and elastase ≥230ng/ml), no significant difference in the levels of ASA was observed compared with the controls (IgG, p =0.1; IgA, p =0.8). Conclusion There is no association between chronic inflammatory or infectious diseases of the MRT and the presence of ASA in semen.

In only approximately 10% of men with symptoms of chronic prostatitis/ chronic pelvic pain syndrome bacterial infection of the prostate can be demonstrated by the Meares and Stamey 4-glass or the pre- and post-prostate massage (PPM) two-glass test. Chronic bacterial prostatitis is mainly caused by Gram-negative uropathogens. The role of Gram-positives, atypicals and anaerobes is still debatable. For treatment, fluoroquinolones are considered the drugs of choice because of their favourable pharmacokinetic properties and their antimicrobial spectrum. As relapse and re-infection are a major problem in chronic bacterial prostatitis, only the results of studies with a follow up period of at least 6 months are meaningful. Analysing the concentrations of various fluoroquinolones in prostatic and seminal fluid as well as in prostatic tissue, it becomes, however, obvious that fluoroquinolones differ not only in plasma concentrations, but also in their penetration ability to these sites. Nevertheless, the concentrations at the site of infection of most fluoroquinolones with this indication should be sufficient for the treatment of chronic bacterial prostatitis caused by susceptible pathogens. On the other hand, male accessory gland infection has been linked to male infertility. However, there is still a lack of evidence showing that bacterial prostatitis would have a negative impact on sperm quality.

There is a consensus on the diagnostic management of bacterial prostatitis (acute and chronic). In chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) the diagnostic approach remains unclear, because inflammatory and noninflammatory CP/CPPS might be one entity with varying findings over time. The WHO definition of male accessory gland infection does not differentiate between prostatitis, epididymitis, and other inflammatory alterations of the urethral compartment. The definition therefore cannot be further accepted as a rational tool for the diagnosis of prostatitis and related diseases in urological andrology. Therapy in infectious prostatitis is standardised and antibiotics are the primary agents. Andrological implications are well defined, side-effects are minimal. CP/CPPS therapy has the goal to reduce pelvic pain. However, treatment regimens are not as standardised. Andrological side-effects are well defined and mainly due to the functional background of these agents.

BACKGROUND: Human sperm contain similar amounts of protamine-1 (P1) and protamine-2 (P2). Although aberrant protamine ratios have been observed in infertile men, functional evidence is provided by protamine knockout mice exhibiting male infertility. As sperm DNA integrity is known to be linked with DNA fragmentation and apoptosis, we investigated whether the protamine ratio or Bcl2 content represent a reliable biomarker to discriminate fertile and infertile men. METHODS: Real-time quantitative RT-PCR was used for P1, P2 and the apoptotic marker Bcl2 in testicular biopsies (TB; 74 infertile men versus 17 controls) and ejaculates (E; 95 infertile men versus 10 controls). RESULTS: The P1-P2 mRNA ratio differed significantly between groups, namely 1:4 versus 1:3.2 in TB (P = 0.0038) and 1:1.7 versus 1:1 in E (P = 0.0002), for infertile men and controls, respectively. Bcl2 mRNA content was correlated with protamine mRNA ratio (P = 0.0250 for TB; P = 0.0003 for E). Infertile men exhibit a more than 10-fold (P = 0.0155 for TB; P = 7.0 x 10 -6 for E) higher Bcl2 mRNA content versus controls. No correlation was found between absolute sperm density and the protamine mRNA ratio or Bcl2 mRNA content. No significant correlation was demonstrated with fertilization rate after ICSI and either protamine ratio or Bcl2 content. CONCLUSIONS: We found significantly aberrant protamine ratios and a higher Bcl2 content in TB and E of infertile men compared to controls, suggesting that these molecules may be useful biomarkers for predicting male infertility.

Objective A broad spectrum of options is available for treatment of Peyronie's disease; however, the effects of minimally invasive therapy are generally inadequate. Although useful, oral drugs must be administered at onset of the disease. Only a few patients request penile surgery. Therefore, new medical treatments for Peyronie's disease are needed. A better understanding of the pathogenesis of Peyronie's disease is required to facilitate development of these new medical treatments. Several studies have described an increased level of TGF-β in the fibrotic plaques of patients with Peyronie's disease, underscoring this important signalling pathway in the onset and/or development of Peyronie's disease. Methods Plaque biopsies were taken from 16 patients with Peyronie's disease. Furthermore, 7 patients without Peyronie's disease were biopsied to provide control material. Fibroblasts were cultured from biopsy tissue, and cultured fibroblasts were stimulated with TGF-β1, BMP-2, IFN-γ, and IFN-γ combined with one of the other stimuli. Protein was extracted from treated fibroblasts and prepared for immunoblots. The membranes were probed for phosphorylated Smad and total Smad to indicate activation of TGF-β signalling. Results An agonistic effect of IFN-γ on TGF-β signalling was observed. Stimulation with TGF-β1 increased levels of phospho-Smad2 and phospho-Smad3. After stimulation with TGF-β1 and IFN-γ combined, the levels of phospho-Smads were higher than those observed with stimulation withTGF-β1 alone. Conclusions The profibrotic effect of TGF-β1 is enhanced by IFN-γ in fibroblasts from patients with Peyronie's disease. The inhibitory effects of IFN-γ on the TGF-β pathway do not appear in Peyronie's disease. Therefore, IFN-γ cannot be taken as a useful tool in the therapy of Peyronie's disease.

The first and rate-limiting step in the biosynthesis of steroid hormones is the transfer of cholesterol into mitochondria, which is facilitated by the steroidogenic acute regulatory (StAR) protein. Recent studies of Leydig cell function have focused on the molecular events controlling steroidogenesis; however, few studies have examined the importance of the mitochondria. The purpose of this investigation was to determine which aspects of mitochondrial function are necessary for Leydig cell steroidogenesis. MA-10 tumor Leydig cells were treated with 8-bromo-cAMP (cAMP) and site-specific mitochondrial disrupters, pro-oxidants, and their effects on progesterone synthesis, StAR expression, mitochondrial membrane potential (delta psi(m)) and ATP synthesis were determined. Dissipating delta psi(m) with CCCP inhibited progesterone synthesis, even in the presence of newly synthesized StAR protein. The electron transport inhibitor antimycin A significantly reduced cellular ATP, inhibited steroidogenesis, and reduced StAR protein expression. The F0/F1 ATPase inhibitor oligomycin reduced cellular ATP and inhibited progesterone synthesis and StAR protein expression, but had no effect on delta psi(m). Disruption of pH with nigericin significantly reduced progesterone production and StAR protein, but had minimal effects on delta psi(m). Sodium arsenite at low concentrations inhibited StAR protein but not mRNA expression and inhibited progesterone without disrupting delta psi(m). The mitochondrial Ca2+ inhibitor Ru360 also inhibited StAR protein expression. These results demonstrate that delta psi(m), ATP synthesis, delta pH and [Ca2+]mt are all required for steroid biosynthesis, and that mitochondria are sensitive to oxidative stress. These results suggest that mitochondria must be energized, polarized, and actively respiring to support Leydig cell steroidogenesis and alterations in the state of mitochondria may be involved in regulating steroid biosynthesis.

Introduction: Nearly 80% of the patients suffering from advanced stages of prostate cancer in Germany are treated currently with luteinizing hormone-releasing hormone (LH-RH) analogs alone or in combination with androgen receptor antagonists. The aim of this study was to assess whether the prescription practice for LH-RH analogs and direct antiandrogens between 1993 and 2003 parallels the rise in the incidence rates for prostate cancer associated with the proportional rise in daily doses. Methods: Between 1993 and 2000 a yearly randomly selected number of receipts has been evaluated from official pharmacies in Germany which have been billed to public health insurance companies. Data concerning drug use, number of daily doses, and total cost of the respective drugs have been calculated by the Research Institute of the AOK (Wissenschaftliches Institut der AOK, WIdO). These prescription data have been related to incidence and mortality rates of patients with prostate cancer. Results: Between 1993 and 2003 the age-standardized incidence rate of carcinomas of the prostate has risen by 180%, while the disease-specific mortality practically has remained nearly at the same level. The daily prescribed doses of LH-RH analogs have risen by a factor of 8.5 from 3.9 to 33.5 million daily doses during this time. In contrast, the daily doses of androgen receptor antagonists have remained unchanged between 1997 and 2001, followed by a rise of 50% between 2001 and 2003. Conclusions: The first analysis of the prescription practice of antiandrogens in the treatment of prostate cancer with respect to the incidence rates in Germany could only be facilitated by the fact that these medications are in exclusive use for this indication in Germany. The rise in prescriptions may be explained by the therapy shift from surgery to LH-RH application until the year 2000; the reasons for a further rise since 2000 remain speculative. In conclusion, only prevalence data would allow the exact calculation of medication needs among prostate cancer patients.

Objective Because the efficacy of nonsurgical therapy of Peyronie's disease is controversial, this review analyses the current status of conservative therapy of Peyronie's disease. Method A systematic survey on results of studies published as original papers in peer-reviewed journals is provided. Results Oral drug therapies include potassium para -aminobenzoate (Potaba), vitamin E, colchicine, tamoxifen, propoleum, acetyl-l-carnitine, and propionyl-l-carnitine. Verapamil, interferon-α2a and interferon-α2b, collagenase, cortisone, hyaluronidase, and superoxide dismutase are considered intralesional therapies that have had various degrees of success. Other treatments include local gels, iontophoresis, extracorporeal shock wave therapy, and radiation. Conclusion This review analyses the current status of the conservative therapy of Peyronie's disease, because the efficacy of the nonsurgical therapy is controversial.

Male genital tract inflammations constitute an important factor of male subfertility in which different mediators are discussed damaging sperm membranes. As acrosome reaction (AR) is ultimately a membrane function, this study aimed at investigating the effects of the chronic pelvic pain syndrome on AR. In a total of 56 patients with chronic pelvic pain syndrome NIH IIIA and NIH IIIB, AR, concentration of leucocytes in ejaculate and urine after prostate massage, sperm concentration, motility, vitality and morphology were determined. The control group (n=95) consisted of patients with normozoospermia and proven absence of signs of inflammation. Compared to the control, both patients groups showed poorer sperm morphology (P

The vitality of spermatozoa used for intracytoplasmic sperm injection (ICSI) is a crucial factor for fertilization, establishment and outcome of a pregnancy in assisted reproductive technique cycles. The sperm origin may also be a limiting factor, although little is known about this issue. It is known that the motility of injected spermatozoa and their origin from ejaculate or testicular biopsies are important predictors in terms of fertilization, pregnancy and birth rates. Oocytes of patients in 2593 cycles were retrieved in our in vitro fertilization programme and inseminated via ICSI. We used motile (group 1, n = 2317) or immotile ejaculated spermatozoa (group 2, n = 79), motile sperm retrieved from testicular biopsies (group 3, n = 62) and immotile spermatozoa from testicular biopsies (group 4, n = 135). Female age and number of oocytes retrieved did not differ significantly among the groups. The fertilization rates were as follows: 67.1% in group 1, 49.8% in group 2, 68.3% in group 3 and 47.8% in group 4. The pregnancy rates in cases where three embryos had been transferred amounted to 35.7% in group 1, 17.3% in group 2, 38.3% in group 3 and 20.5% in group 4. The embryo quality showed no differences between groups 1 and 3 (14.5), and between groups 2 (11.8) and 4 (10.8). The abortion rate was similar in groups 1-3, but increased in group 4 (26.6%, 27.3%, 31.6% and 55.5%). Irrespective of their origin, the fertilization potential of injected spermatozoa was found to be influenced by motility. The resulting pregnancy and birth rates, i.e. the potential of the resulting embryos to implant and to achieve viable pregnancies, seem to be additionally dependent on the sperm origin. This was well shown by declining rates when spermatozoa in a relatively early stage of maturity had been used. We see increasing evidence that the degree of sperm maturity has an important impact on the outcome of ICSI. In obstructive azoospermia, spermatozoa retrieved from the epididymis should be used rather than testicular biopsy spermatozoa, or testicular sperm should be preincubated in culture medium before ICSI.

Extracorporeal shock wave therapy (ESWT) for the treatment of Peyronie's disease is still controversial. This exploratory meta-analysis of published studies in the international literature investigates its therapeutic effects.The treatment outcomes from 17 study groups identified by a computerized literature search were compared with natural history outcomes and data from control groups from 2 controlled ESWT studies. An exploratory meta-analysis was performed because a methodologically sound meta-analysis lege artis did not appear appropriate, since treated groups differ considerably in structure, the selection of outcome measures is inconsistent and measurement is not standardized.ESWT seems to have an effect on penile pain during erection and on the improvement of sexual function. Pain seems to resolve faster after ESWT than during the course of the natural history. The effect on plaque size and penile curvature is less impressive.ESWT in Peyronie's disease at least seems to be effective in regard to penile pain and sexual function compared to natural history. Deducing from these data the effect on plaque size and curvature remains questionable. However, ESWT is not an evidence based therapy at present. A controlled (preferably pairwise matched), single blind, multicenter study with careful, detailed documentation of disease symptoms before intervention and of outcomes is required to evaluate the real effect of ESWT.

Male accessory sex gland infections are considered as potential hazards to male fertility. Various pathophysiological concepts have evolved from experimental and clinical studies that begin to explain the effects of bacteria and immunological events on the function of spermatozoa and sperm motility in particular. Besides direct influences of pathogenic bacteria on spermatozoa whose impact on the motility of human spermatozoa is reviewed herein, recent studies have identified and evaluated infectious mediators that appear to be responsible for specific molecular processes in infections that particularly affect the motility of spermatozoa. This review will focus in detail on direct bacterial effects of sperm motility, the role of seminal leucocytes and the impact of pro-inflammatory cytokines on the motility of spermatozoa.

Reactive oxygen species (ROS) are involved in a variety of pathophysiological conditions of the testis, and oxidative stress is known to inhibit ovarian and testicular steroidogenesis. The site of ROS-mediated inhibition of steroidogenesis in the corpus luteum and MA-10 tumor Leydig cells was shown to be the hormone-sensitive mitochondrial cholesterol transfer step. The purpose of this study was to examine the effects of ROS on steroidogenic acute regulatory (StAR) protein in MA-10 cells and determine the extent to which MA-10 cell mitochondria are sensitive to oxidative stress. cAMP-stimulated progesterone production was inhibited in a dose-dependent manner in MA-10 cells exposed to H(2)O(2). StAR protein, but not mRNA levels, was decreased in parallel to changes in progesterone production. Even at the highest concentrations of H(2)O(2) tested, there was no effect on P450 side-chain cleavage enzyme protein levels. Oxidative stress from exposure to exogenous xanthine oxidase and xanthine resulted in the inhibition of both progesterone production and StAR protein expression. The mature 30- and 32-kDa intramitochondrial forms of StAR were decreased relative to the 37-kDa extramitochondrial precursor form of StAR, indicating that the ROS-mediated inhibition of StAR protein was due, in part, to the inhibition of mitochondrial import and processing. Vital staining with the fluorescent dye tetramethylrhodamine ethyl ester was used to visualize changes in the mitochondrial electrochemical gradient-dependent membrane potential (Deltapsim). ROS caused a significant dissipation of Deltapsi(m) and time-dependent loss of tetramethylrhodamine ethyl ester fluorescence. The inhibitory effects of H(2)O(2) were transient. There was no evidence for ROS-induced cell death, and following H(2)O(2) removal in the presence of continuous treatment with 8-bromo-cAMP, StAR protein levels and progesterone production were restored. In addition, there was no loss of cell viability following treatment with H(2)O(2) or xanthine/xanthine oxidase as determined by trypan blue exclusion. H(2)O(2) did not cause a significant decrease in total cellular ATP levels. These data indicate that oxidative stress-mediated perturbation of the mitochondria and dissipation of Deltapsi(m) results in the inhibition of StAR protein expression and its import, processing, and cholesterol transfer activity. These findings confirm earlier studies demonstrating the requirement for maintenance of an intact Deltapsi(m) for StAR protein function in cholesterol transport. The significant reduction in the 32- to 30-kDa mature forms of StAR, cessation of cholesterol transport, and loss of Deltapsi(m) are consistent with mitochondrial perturbation because of oxidative stress. This mechanism likely contributes to a host of pathophysiological events evident in testicular disorders such as infection, reperfusion injury, aging, cryptorchidism, and varicocele.

Objective: The aim of the study was to evaluate the secretory dysfunction of the male accessory glands in men with inflammatory versus non-inflammatory chronic pelvic pain syndrome (CPPS). Methods: One hundred and twelve consecutive patients symptomatic for chronic pelvic pain were included into the study. All underwent a combined granulocyte analysis in expressed prostatic secretions (EPS) and a four-glass-test followed by ejaculate analysis. Patients were subgrouped according to elevated granulocyte counts in prostatic secretions, leukocytes in semen, or any of both. The content/total enzyme activity of the secretory seminal plasma parameters γ-glutamyl-transferase (γ-GT), fructose, and α-glucosidase representing the secretory capacity of the prostate gland, the seminal vesicles, and the epididymes, respectively, were investigated. Results: The only significant findings were a reduced total enzyme activity of γ-GT in men stratified according to elevated granulocyte counts in prostatic secretions ( p =0.022; cutpoint 9.85U per ejaculate; sensitivity 61.1%, specificity 58.8%, AUC 0.6347) and in men with any inflammatory sign ( p =0.033; cutpoint 9.9U per ejaculate, sensitivity 63%, specificity 58.33%, AUC 0.6404). Conclusions: Secretory damage of the prostate gland in men with inflammatory CPPS is demonstrable provided that increased granulocytes in prostatic secretions are part of the diagnostic criteria. However, because of the low sensitivity and specificity of γ-GT it cannot be recommended as diagnostic tool to detect inflammatory disease on the basis of reduced secretory capacity.

Immune activation results in the activation of adrenal steroidogenesis and inhibition of gonadal steroidogenesis. Previous studies indicated that these effects were caused primarily by activation and suppression of the secretion of ACTH and LH, respectively. However, other evidence indicated a direct effect of the immune system on the gonads. In this study, serum testosterone, quantitated by RIA after lipopolysaccharide injection, showed a significant decrease within 2 h. Parallel measurement of serum LH showed no change. There were no differences in LH receptor or cAMP produced in Leydig cells between vehicle- and lipopolysaccharide-injected mice. The 30-kDa form of the steroidogenic acute regulatory (StAR) protein was quantitated, by Western blot, in Leydig cells and was found to decrease in a time-dependent manner. No change in StAR protein messenger RNA (mRNA) was detected by Northern analysis during this time, nor were any changes found in the levels of mRNA for the steroidogenic enzymes P450scc, 3β-hydroxysteroid dehydrogenaseΔ 4-Δ5-isomerase, or P450c17. In the adrenal, StAR protein was increased, as was StAR protein mRNA. No changes were observed in the levels of mRNA for P450scc, 3β-hydroxysteroid dehydrogenaseΔ 4-Δ5-isomerase, or P450c21. Thus, although the mechanisms of regulation differ, changes in the levels of StAR protein are a sensitive indicator of the steroidogenic capacity of these two tissues.

Male accessory sex gland infections are considered to be hazards to male fertility. Various pathophysiologic concepts have evolved from experimental and clinical studies that begin to explain the effects of bacteria and immunologic events on spermatozoa. Recent studies have identified and evaluated mediators that are responsible for specific molecular processes in infections that particularly affect the function of spermatozoa.

Summary. The influence of different uropathogenic microorganisms (E. coli, enterococcus, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Candida albicans) on human sperm motility was studied in vitro with a computer-assisted sperm analyser (CASA). Native ejaculates were prepared with the swim-up technique and adjusted to 22 times 106 spermatozoa ml−1. The sperm suspension was artificially infected with microorganisms in concentrations varying from 2 times 103 to 2 times 107. Sperm motility was examined directly after incubation, 2, 4 and 6 h later using the Mika motion analysis®, a computer-based, automatic motility analysis. Former results with E. coli (serotype 06) could be confirmed that a significant inhibitory effect on sperm motility was associated with bacterial growth. Experiments with the enterococcus strain and Staphylococcus saprophyticus indicated no significant influence on sperm motility parameters. Tests with Pseudomonas aeruginosa showed a decrease of progressive motility according to time, but not to different bacterial concentrations. A significant inhibitory effect of Candida albicans was only detected in the samples with the initial bacterial concentration of 2 times 107 microorganisms ml−1.

The influence of E. coli on human sperm motility was studied in vitro. Semen samples were prepared by a swim-up technique and adjusted to 22 x 10(6) spermatozoa/ml. Samples were then inoculated with different concentrations of a uropathogenic strain of E. coli, serotype 06, with initial sperm/bacteria ratios varying between 10:1 and 10000:1. Motion parameters were analysed by computer-aided motility analysis directly, and 2, 4 and 6 h after inoculation. In a second series of experiments, bacterial replication was inhibited by addition of chloramphenicol. In a third series, the effect of E. coli culture filtrates on sperm motility was investigated. The direct inhibitory effect of E. coli on progressive motility of spermatozoa was found to depend upon the bacterial concentration. A distinct inhibitory effect was observed only at a sperm/bacteria ratio of approximately 1, achieved by growth of E. coli during the experiments. For modality of motion, no distinct changes were observed. When growth of bacteria was prevented by chloramphenicol, no inhibitory effect on sperm motility was detected. Sperm motility was not inhibited by E. coli culture filtrates. Analysis by electron microscopy revealed multiple adhesions of E. coli to spermatozoa, causing variable ultrastructural damage as probable morphological correlates of immobilization.