W. Weidner

Investigation, Treatment, and Monitoring of Late-Onset Hypogonadism in Males: ISA, ISSAM, EAU, EAA, and ASA Recommendations

The new ISA, ISSAM, EAU, EAA and ASA recommendations on the investigation, treatment and monitoring of late-onset hypogonadism in males provide updated evidence-based information for clinicians who diagnose and treat patients with adult onset, age related testosterone deficiency.

Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations

Demographic data clearly demonstrate that the percentage of the population in the older age group is increasing. Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. Cross-sectional and longitudinal data indicate that the testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adult (age 20–30 years) men (1–4). The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment of hypogonadal men on multiple target organs and the recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. This has been comprehensively reviewed and summarized by the Institute of Medicine in ‘Testosterone and Aging: Clinical Research Directions’ (5). Long-term data on the effects of testosterone treatment in the older population are limited mainly to effects on body composition and bone mass (6–11). Key questions of the effects of testosterone on patient reported outcomes and functional benefits that may retard physical or mental frailty of the elderly or improve the quality of life are not yet available. Specific risk data on the prostate and cardiovascular systems are needed.

Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair.

CONTEXT Varicocele is a common condition, found in many men who present for infertility evaluation. OBJECTIVE To assess the effect of varicocelectomy on male infertility. EVIDENCE ACQUISITION A literature search was performed using Embase and Medline. Literature reviewed included meta-analyses and randomized and nonrandomized prospective (controlled and noncontrolled) studies. In addition, a new meta-analysis was performed. EVIDENCE SYNTHESIS Four randomized controlled trials reporting on pregnancy outcome after repair of clinical varicoceles in oligozoospermic men were identified. Using the random effect model, the combined odds ratio was 2.23 (95% confidence interval [CI], 0.86-5.78; p=0.091), indicating that varicocelectomy is moderately superior to observation, but the effect is not statistically significant. We identified 22, 17, and 5 prospective studies reporting on sperm concentration, total motility, and progressive motility, respectively, before and after repair of clinical varicocele. The random effect model combined improvement in sperm concentration was 12.32 million sperm per milliliter (95% CI, 9.45-15.19; p<0.0001). The random effect model combined improvement in sperm total and progressive motility were 10.86% (95% CI, 7.07-14.65; p<0.0001) and 9.69% (95% CI, 4.86-14.52; p=0.003), respectively. These results indicate that varicocelectomy is associated with a significant increase in sperm concentration as well as total and progressive motility. Prospective studies also show that varicocelectomy reduces seminal oxidative stress and sperm DNA damage as well as improving sperm ultramorphology. Studies indicate that a microsurgical approach to a varicocele repair results in less recurrence and fewer complications than other techniques. CONCLUSIONS Although there is no conclusive evidence that a varicocele repair improves spontaneous pregnancy rates, varicocelectomy improves sperm parameters (count and total and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology. The various methods of repair are all viable options, but microsurgical repair seems to be associated with better outcomes.

Infective Complications After Prostate Biopsy: Outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, A Prospective Multinational Multicentre Prostate Biopsy Study

BACKGROUND Infection is a serious adverse effect of prostate biopsy (P-Bx), and recent reports suggest an increasing incidence. OBJECTIVE The aim of this multinational multicentre study was to evaluate prospectively the incidence of infective complications after P-Bx and identify risk factors. DESIGN, SETTING, AND PARTICIPANTS The study was performed as an adjunct to the Global Prevalence Study of Infections in Urology (GPIU) during 2010 and 2011. Men undergoing P-Bx in participating centres during the 2-wk period commencing on the GPIU study census day were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Baseline data were collected and men were questioned regarding infective complications at 2 wk following their biopsy. The Fisher exact test, Student t test, Mann-Whitney U test, and multivariate regression analysis were used for data analysis. RESULTS AND LIMITATIONS A total of 702 men from 84 GPIU participating centres worldwide were included. Antibiotic prophylaxis was administered prior to biopsy in 98.2% of men predominantly using a fluoroquinolone (92.5%). Outcome data were available for 521 men (74%). Symptomatic urinary tract infection (UTI) was seen in 27 men (5.2%), which was febrile in 18 (3.5%) and required hospitalisation in 16 (3.1%). Multivariate analysis did not identify any patient subgroups at a significantly higher risk of infection after P-Bx. Causative organisms were isolated in 10 cases (37%) with 6 resistant to fluoroquinolones. The small sample size per participating site and in compared with other studies may have limited the conclusions from our study. CONCLUSIONS Infective complications after transrectal P-Bx are important because of the associated patient morbidity. Despite antibiotic prophylaxis, 5% of men will experience an infective complication, but none of the possible factors we examined appeared to increase this risk. Our study confirms a high incidence of fluoroquinolone resistance in causative bacteria.

Chronic orchitis: a neglected cause of male infertility?

Infection and inflammation of the male reproductive tract are accepted as important aetiological factors of infertility. With regard to their impact on male reproductive function, orchitis and epididymo‐orchitis due to local or systemic infection as well as noninfectious aetiological factors are of particular concern. There is clinical and pathological evidence that chronic inflammatory conditions of the testes can disrupt spermatogenesis and irreversibly alter both sperm number and quality. In the majority of patients, however, diagnosis is hampered by an asymptomatic course of the disease and unspecific clinical signs. Hence, respective epidemiological data are scarce. On the other hand, systematic histopathological work‐up of testicular biopsies from infertile men indicates a high prevalence of inflammatory reactions. A characteristic pattern of inflammatory lesions with focal or multifocal, predominantly peritubular lymphocyte infiltration and concomitant damage of seminiferous tubules is seen in chronic orchitis of various origins. This supports the concept that induction of testicular inflammation is associated with a T‐cell‐mediated autoimmune response, i.e. disruption of the immune privilege. Moreover, despite the patchy distribution of the lesions, testicular volume and score counts for spermatogenesis may be significantly reduced. In conclusion, asymptomatic inflammatory reactions in the testis should not be neglected as an underlying cause or co‐factor of male infertility. However, definitive diagnosis of chronic asymptomatic orchitis still requires testicular biopsy and guidelines for the therapeutic management are not yet available.

Investigation, treatment and monitoring of late-onset hypogonadism in males.

*Corresponding Author Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. The demographics clearly demonstrate the increasing percentage of the population that is in the older age groups. The data also support the concept that testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adults (age 20-30 years) men. The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment on multiple target organs of hypogonadal men and recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. Long-term data on the effects of testosterone treatment in the older population are limited and specific risk data on the prostate and cardiovascular systems are needed. Answers to key questions of functional benefits that may retard frailty of the elderly are not yet available. The recommendations described below were prepared for the International Society of Andrology (ISA) and the International Society for the Study of the Aging Male (ISSAM) following a panel discussion with active participation from the audience sponsored by the ISA on the topic at the 4th ISSAM Congress in Prague in February 2004. The ISA Member Societies were requested to comment on the draft recommedations. Representatives of the European Association of Urology (EAU) participated in the final draft of this document. This document is not intended to provide evidence for each recommendation as review of pertinent studies have recently been comprehensively summarized in the Clinical Research Directions on “Testosterone and Aging” by the Institute of Medicine (Washington 2004). The recommendations will be subject to revision as larger-scale and longer-term data become available. In order to reach a large audience these recommendations are published in the International Journal of Andrology,the Journal of Andrology, The Aging Male and in European Urology. E Nieschlag * Institute of Reproductive Medicine University of Münster, Germany Email: eberhard.nieschlag@ukmuenster.de

Treatment-related stresses and depression in couples undergoing assisted reproductive treatment by IVF or ICSI.

Summary. The purposes of the study were to compare treatment‐related stresses of couples undergoing IVF or ICSI treatment (ejaculated, epididymal or testicular spermatozoa) and to identify sex differences and risk factors for depression. A one‐year cohort of couples was retrospectively sent questionnaires on infertility and treatment‐related distress and depression (Depression Scale, D‐S). Two hundred and eighty‐one women and 281 men (61% of those eligible) were included. As determined by analysis of the medical charts, successful couples were more likely to participate. Treatment‐related distress was generally higher for women than for men. Treatment by ICSI carried additional burdens for the men: they reported a greater subjective responsibility for the infertility, impact of childlessness on daily life, treatment‐related stresses (particularly for MESA/TESE) and time demands. Even when clinical differences between treatments (e.g. age, previous treatments) were controlled statistically, depression scores did not differ. Independent of the treatment, women were significantly more depressed than their agematched female controls from the general population and their husbands. The men only reported marginally elevated depression scores compared to their controls. Meaningful characteristics were identified that could guide clinicians to give psychological support to those couples at risk for depression, e.g. an unsuccessful treatment outcome, repeated treatment cycles, a low socioeconomic status, foreign nationality, or, for women, a lack of partner support.

ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males

Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles BioMedical Research Institute, Torrance, CA, USA, Centre for Reproductive Medicine and Andrology, University of Muenster, Muenster, Germany, Center for Reproductive Medicine and Andrology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany, Department of Urology, Tulane University, New Orleans, LA, USA, Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands, Department of Endocrinology, Academish Ziekenhuis, Gent, Belgium, Centre Hospitalier Universitaire, Sart-Tilman, Liege, Belgium, Faculty of Life Science, Bar-Ilan University, Ramat-Gan, Israel, Centre for Applied Urological Research, Queen’s University, Kingston, Canada, Division of Geriatric Medicine, St. Louis University and GRECC, St. Louis VA Medical Center, St. Louis, MO, USA, Department of Urology, Erasme Hospital, University Clinics Brussels, Brussels, Belgium, Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA, Department of Urology and Pediatric Urology, University Hospitals, Justus-Liebig-University, Giessen, Germany, and Department of Endocrinology, University of Manchester, Manchester Royal Infirmary, Manchester, UK

Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions.

OBJECTIVES Chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a disorder characterized by pelvic pain and varying degrees of inflammation exhibited in expressed prostatic secretions (EPS). To provide objective parameters of inflammation, we measured the cytokines interleukin 8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) in EPS of healthy men, men with benign prostatic hyperplasia (BPH), men with bacterial prostatitis (BP), and men with chronic prostatitis/CPPS. METHODS Enzyme-linked immunosorbent assays of the EPS for IL-8 and ENA-78 were done in 63 men: control (n = 9), BPH (n = 6), BP (n = 3), inflammatory CPPS (National Institutes of Health [NIH] category IIIa) (n = 17), noninflammatory CPPS (NIH category IIIb) (n = 17), and asymptomatic inflammatory prostatitis (NIH category IV) (n = 11). RESULTS IL-8 was detectable in all patients, and ENA-78 was detectable in all except 2 patients (threshold of detection 10 pg/mL for IL-8, 15 pg/mL for ENA-78). Mean levels of IL-8 [ENA-78] were similar in control (3010 pg/mL [423 pg/mL]), BPH (3341 pg/mL [98 pg/mL]), and IIIb (2751 pg/mL [335 pg/mL]) groups. Both cytokine levels were higher in BP (11,175 pg/mL [13,761 pg/mL]), IIIa (10,418 pg/mL [2240 pg/mL]), and IV (8571 pg/mL [1865 pg/mL]) groups. A statistically significant difference between the control group versus BP, IIIa, and IV (P <0.05) groups was found for IL-8 but not for ENA-78. CONCLUSIONS IL-8 and ENA-78 are frequently elevated in the EPS of men with BP, CPPS IIIa, and asymptomatic inflammatory prostatitis category IV. These cytokines are direct mediators of leukocyte accumulation and activation at inflammatory sites and may be responsible, in part, for the presence of inflammatory reaction in the prostate.

A Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis–Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study

BACKGROUND National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. OBJECTIVES To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. DESIGN, SETTING, AND PARTICIPANTS We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. INTERVENTION Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. MEASUREMENTS The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. RESULTS AND LIMITATIONS In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. CONCLUSIONS Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.