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Purpose: Advanced forms of prostate cancer (PCa) radiotherapy with either external beam therapy or brachytherapy delivery techniques aim for a focal boost and thus require accurate lesion localization and lesion segmentation for subsequent treatment planning. This study prospectively evaluated dynamic contrast-enhanced computed tomography (DCE-CT) for the detection of prostate cancer lesions in the peripheral zone (PZ) using qualitative and quantitative image analysis compared to multiparametric magnet resonance imaging (mpMRI) of the prostate., Methods: With local ethics committee approval, 14 patients (mean age, 67 years; range, 57-78 years; PSA, mean 8.1 ng/ml; range, 3.5-26.0) underwent DCE-CT, as well as mpMRI of the prostate, including standard T2, diffusion-weighted imaging (DWI), and DCE-MRI sequences followed by transrectal in-bore MRI-guided prostate biopsy. Maximum intensity projections (MIP) and DCE-CT perfusion parameters (CTP) were compared between healthy and malignant tissue. Two radiologists independently rated image quality and the tumor lesion delineation quality of PCa using a five-point ordinal scale. MIP and CTP were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis., Results: The PCa detection rate ranged between 57 to 79% for the two readers for DCE-CT and was 92% for DCE-MRI. DCE-CT perfusion parameters in PCa tissue in the PZ were significantly different compared to regular prostate tissue and benign lesions. Image quality and lesion visibility were comparable between DCE-CT and DCE-MRI (VGC: AUC 0.612 and 0.651, p>0.05)., Conclusion: Our preliminary results suggest that it is feasible to use DCE-CT for identification and visualization, and subsequent segmentation for focal radiotherapy approaches to PCa., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the frequency of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in patients with castration-resistant prostate cancer (CRPC) and lower urinary tract symptoms (LUTS)., Patients and Methods: Our prospective urodynamics database was queried. Inclusion criteria were CRPC and an International Prostate Symptom Score (IPSS) ≥ 20. Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS. Twenty-one patients were identified. Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement (BPE)., Results: The median age of patients in the CRPC group was 74 years, and the median prostate-specific antigen (PSA) level at the time of the urodynamic study was 90 ng/mL. According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed. DO was seen in 12 patients (57%). Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities (P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028)., Conclusions: This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO. LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity. A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates. Larger prospective studies are needed to confirm our findings., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To evaluate ABO blood group as a prognostic marker in patients with renal cell carcinoma (RCC)., Patients and Methods: This retrospective study included 556 consecutive patients who underwent surgery for RCC at a single institution. The associations of ABO blood group with clinical and pathological variables were assessed using Kruskal-Wallis and chi-squared tests. The impact on overall survival (OS) and RCC-specific survival (RCC-SS) was analysed using univariable and multivariable Cox proportional hazards regression models., Results: Blood group O was associated with the absence of lymph node metastases (P = 0.034) and the presence of bilateral RCC (P = 0.017). No associations with age, gender, body mass index, Charlson comorbidity index, T stage, M stage, grade and histological subtype were observed. In univariable and multivariable survival analysis, ABO blood group was not associated with OS and RCC-SS., Conclusions: In the present study, ABO blood group was not linked with RCC prognosis. Blood group O may be associated with the absence of lymph node metastases and the presence of bilateral RCC. External validation in larger cohorts is necessary., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To evaluate the prostate cancer (PCa) detection rate, PCa location, PCa significance and complications of a standardized 24-core template-guided transperineal biopsy (TPB) approach in patients with at least two negative transrectal biopsies., Methods: We prospectively recruited 50 men who had at least two negative transrectal ultrasound-guided extended biopsies in the past 24 months, a prostate-specific antigen (PSA) < 20 ng/mL, a prostate volume < 100 mL, and life expectancy of at least 90 % at 10 years. All patients underwent a standardized 24-core template-guided TPB biopsy. The PCa detection rate, PCa location, PCa significance, and complications were recorded., Results: Median age was 57.5 years and the median PSA level was 7.3 ng/ml. PCa was detected in 24 patients (48 %). The anterior zone was involved in 16 (32 %) PCa. Six PCa (25 %) were insignificant. Biopsy related complications occurred in 2 patients (4 %)., Conclusions: A 24-core TPB is a safe procedure with a high PCa detection rate. Few of the detected PCa are clinically insignificant. Men with at least two negative transrectal biopsies may be counseled to undergo TPB.

Purpose: PAR-1 mediates angiogenesis and impacts the process of tumor growth and disease progression. We evaluated the associations of the gene variations PAR-1 IVSn -14 A>T (rs168753), -506 Ins/Del (rs11267092) and -1426 C>T (rs32934) with renal cell carcinoma pathology and cancer specific survival., Materials and Methods: DNA was extracted from the peripheral blood leukocytes of 236 consecutive patients with renal cell carcinoma. Genotyping was done using restriction fragment length polymorphism analysis of polymerase chain reaction amplicons and sequencing., Results: The IVSn -14 AA genotype was associated with a 3.13-fold increased risk of distant metastases (p = 0.015). In addition, cancer specific survival of patients with IVSn -14 AA was significantly worse than in those with AT/TT (HR 2.98, p = 0.019). The 1 and 4-year cancer specific survival rate for AA vs AT/TT was 89% vs 99% and 82% vs 92%, respectively. After adjusting for the stage, size, grade and necrosis (SSIGN) score on multivariable analysis, IVSn -14 AA was identified as an independent adverse prognostic factor (HR 2.72, p = 0.044). The variations -506 Ins/Del and -1426 C>T were not significantly associated with pathological factors or cancer specific survival., Conclusions: Results suggest that the AA genotype of the PAR-1 variation IVSn -14 A>T is associated with an increased risk of metastasis and poorer prognosis of renal cell carcinoma. Therefore, assessing the individual risk based on genotypes may be a helpful adjunct to identify subgroups at high risk for a poor clinical outcome., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the perception of colicky pain due to ureteral stones and double-J (DJ)-associated discomfort and to evaluate the role of clinical parameters that might influence the perception of pain., Materials and Methods: From November 2011 to May 2012, 124 consecutive patients with colicky pain due to ureteral stones and ureteroscopic stone extraction underwent DJ stent placement. A visual analog scale (VAS) was used to assess the pain at ureteral colic, during indwelling DJ stent, and at DJ stent removal. The association of clinical data with pain scores was also analyzed., Results: Pain perception at the time of colic did not vary according to sex (P = .804), age (P = .674), or DJ stent length (P = .389). Stone size (<4 mm) was a predictor of a high VAS score (P = .001). Patients with recurrent stone formation had significantly less pain at the time of colic (P = .004), and DJ stent removal (P = .004) than those with the first instance of stone formation. The clinical experience at cystoscopic DJ stent removal influenced pain perception (P <.001)., Conclusion: Using a VAS for the evaluation of pain perception is a valid method for the objectification of subjective discomfort. The VAS is an easy to administer scale and provides accurate information on the patients' status. Additional studies with larger cohorts focusing on pain perception using the VAS and other validated questionnaires are recommended to produce more consistent data., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Caspase-8 is a key regulator of apoptosis. Its cancer cell antigen induced cell death activity is strongly impacted by the insertion/deletion promoter polymorphism CASP8 -652 6N ins/del (rs3834129). We studied the association of this polymorphism with renal cell carcinoma risk and pathology., Materials and Methods: In this hospital based case-control study 500 Austrian patients were genotyped, including 250 with renal cell carcinoma, and 250 age and gender matched healthy controls. Polymerase chain reaction amplified genomic DNA was evaluated by restriction fragment length polymorphism analysis and automatic sequencing. We assessed associations with renal cell carcinoma risk and pathological factors, and performed a meta-analysis of the literature., Results: The CASP8 -652 6N ins/del polymorphism was significantly linked to renal cell carcinoma (chi-square for trend = 9.50, p = 0.002). Compared with ins/ins, del/del was associated with a 57% decreased risk of the disease (OR 0.43, 95% CI 0.26-0.73, p = 0.002). Furthermore, del/del was associated with a lower risk of distant metastases (p <0.05) but not with T stage, N stage or grade. On meta-analysis the CASP8 -652 6N ins/del polymorphism was associated with renal cell carcinoma risk (p <0.001)., Conclusions: The del/del genotype of the CASP8 -652 6N ins/del promoter polymorphism decreases the overall risk of renal cell carcinoma. It may be associated with a decreased risk of metastasis. Larger studies are warranted to validate our findings., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To validate high-sensitivity C-reactive protein (hs-CRP) serum levels as an independent marker for disease-free survival (DFS) in clinically localised clear cell renal cell carcinoma (ccRCC)., Patients and Methods: In all, 403 consecutive patients with clinically localised (T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled. Preoperative serum levels of hs-CRP were evaluated as both a continuous and categorical variables. Associations with clinical (age, gender) and pathological variables (T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal-Wallis tests. Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy (PA) was assessed with Harrell's C-index., Results: The mean hs-CRP level was 1.32 mg/dL. The hs-CRP levels were associated with T classification (P = 0.05), high-grade disease (P < 0.001) and tumour necrosis (P = 0.003). After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs-CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015). The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence. These categorically coded hs-CRP levels were identified as independent prognostic factors in multivariable analyses (P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' (SSIGN) score., Conclusions: This study validates preoperative serum hs-CRP levels as independent prognostic factor after surgery for localised ccRCC. Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials., (© 2013 BJU International.)

Telomere dysfunction is an early event in the development of prostate cancer and telomerase (TERT) activity is detectable in the majority of prostate cancers. Genetic variation in TERT and its regulatory elements may influence prostate carcinogenesis. MNS16A, a functional polymorphic tandem repeat minisatellite of TERT, has been studied in several malignancies. We determined MNS16A genotypes in an Austrian case-control study for the first time in the context of prostate cancer, comprising 1165 prostate cancer cases and 674 benign prostate hyperplasia controls with PCR. In addition to the five reported variable number of tandem repeats (VNTRs), we identified VNTR-212, a rare variant, for the first time in a European population. Multiple logistic regression analysis revealed no differences in genotype distribution between cases and controls. However, in stratified analysis, MNS16A VNTR-274 (OR = 0.25, 95% CI = 0.06-0.79, P = 0.016) and genotype 274/302 (OR = 0.13, 95% CI = 0.01-0.58, P = 0.005) were associated with a significantly decreased risk of prostate cancer in the age group >70 years. Our finding of a MNS16A genotype conferring a protective effect against prostate cancer in older men suggests a potential role of this polymorphism in prostate cancer susceptibility but demands to be validated in further studies.

Background: Solid organ recipients have a substantial risk of developing bladder cancer, with high-risk non-muscle-invasive bladder cancer (NMIBC) being the most frequent diagnosis. Theoretically, adjuvant bacillus Calmette-Guérin (BCG) therapy is contraindicated, but limited data indicate its feasibility. The objective of this study was to evaluate the safety and efficacy of BCG following solid organ transplantation., Materials and Methods: We reviewed the data of four solid organ recipients who received adjuvant BCG for high-risk NMIBC at our institution. Additionally, individual data of 12 patients were extracted from case series and case reports, which were identified through a systematic review of the literature. A meta-analysis was performed., Results: Fourteen patients (88 %) had received a kidney, one a heart, and one a liver transplant. The median time from transplantation to bladder cancer was 60.5 months. The regimen of immunosuppression was not modified in 12 patients (75 %). Forty-two percent of patients did not receive prophylactic antibiotics, and 70 % had no side effects. Ten patients (63 %) experienced recurrence after a median of 14 months. Progression to muscle-invasive or metastatic disease was observed in two patients (13 %). Four patients (25 %) underwent radical cystectomy, and two patients died of the disease., Conclusions: BCG therapy is a safe option for patients with high-risk NMIBC following solid organ transplantation. However, there is a substantial risk of recurrence and progression. Urologists and patients considering BCG therapy should be aware of this and may consider early cystectomy. There is no evidence to support the need for prophylactic antibiotics.

Objective: To evaluate the prevalence and genotypes of high-risk human papilloma virus (HPV) infection of the foreskin in asymptomatic boys before first sexual intercourse., Materials and Methods: We collected 50 consecutive foreskin specimens after radical circumcision. Indication for surgery was phimosis. High-risk HPV status was determined by real-time polymerase chain reaction for the genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Immunohistochemistry for p16(INK4a) was performed., Results: The median age at the time of surgery was 5.5 years (range, 5 months-15 years). High-risk HPV was detected in 6 of 50 foreskins (12%). All positive samples showed HPV16. No association with age or grade of phimosis was observed. Two samples were focally positive for p16(INK4a), both of which were HPV-negative., Conclusion: In a significant proportion of boys, subclinical high-risk HPV infections are found in the foreskin, which could be a reservoir for HPV-associated diseases. Our study generates the hypothesis that nonsexual routes play significant roles in HPV transmission. Because the human foreskin represents a high-risk HPV reservoir, vaccination may be also advised in boys., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: Study Type--Symptom prevalence (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Depression plays an important role in pathogenesis of BPH. Our study shows that prostatic symptoms can be helpful in the screening for depression., Objective: • To evaluate the relationship between lower urinary tract symptoms (LUTS) and depression in men through validated questionnaires., Patients and Methods: • Healthy male workers (n = 673) were invited to a free health check-up. • Patients underwent a detailed medical examination. • All participants completed the International Prostate Symptom Score (IPSS) questionnaire and the Beck Depression Inventory (BDI)., Results: • Under multiple logistic regression analysis (adjusted for total testosterone and age), a significant effect of IPSS on BDI score was observed: mild depression (BDI score >9): odds ratio (OR) 1.092, 95% confidence interval (CI) 1.056-1.129; P < 0.001; moderate-to-severe depression (BDI score >19): OR 1.093, 95% CI 1.031-1.159; P = 0.003; and severe depression (BDI score >29): OR 1.176, 95% CI 1.048-1.320; P = 0.006., Conclusions: • In healthy men, LUTS are significantly associated with depression. • The treatment of LUTS is very important for the mental health of older men., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Purpose: We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer., Materials and Methods: This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE®, EMBASE® and Web of Science®. The records of 740 patients from a total of 7 studies were finally analyzed., Results: Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable., Conclusions: Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We studied the association of serum sex hormone levels with clinicopathological variables and biochemical recurrence in men with prostate cancer treated with radical prostatectomy., Materials and Methods: We prospectively studied preoperative serum sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and free and total testosterone in 372 patients undergoing radical prostatectomy. Biochemical recurrence was analyzed in 285 patients and defined as prostate specific antigen 0.2 ng/ml or higher at least 30 days after radical prostatectomy. Median followup was 43.6 months., Results: Median sex hormone-binding globulin was 37.4 nmol/l, luteinizing hormone 4.1 mU/ml, follicle-stimulating hormone 5.9 mU/ml, and free and total testosterone 0.069 and 3.7 ng/ml, respectively. There was no significant association of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone or total testosterone with T and N stage, and margin status. Luteinizing hormone, follicle-stimulating hormone, and free and total testosterone were not associated with biochemical recurrence. In contrast, for each 10 U increase in sex hormone-binding globulin the risk of biochemical recurrence increased by 12% (p = 0.045). On multivariable analysis sex hormone-binding globulin achieved independent predictor status after adjusting for standard clinicopathological variables. After stepwise regression a model containing T and N stage, Gleason score, margin status, prostate weight and sex hormone-binding globulin improved the accuracy of a base model by 1.3% (79.0% vs 77.7%)., Conclusions: Preoperative serum sex hormone-binding globulin is independently associated with biochemical recurrence after radical prostatectomy and increases the predictive accuracy of a standard multivariable model. Routine assessment of sex hormone-binding globulin sex hormone-binding globulin may be a helpful adjunct to identify patients who need early adjuvant therapy., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the impact of age on PCA3 score and the utility of age-specific reference values in predicting initial prostate biopsy (pBx) outcomes., Patients and Methods: This single-center, retrospective study included 205 men who underwent an initial 14-core TRUS-guided pBx due to PSA > 3.0 ng/ml or suspicious digital-rectal examination (DRE). PCA3 scores were measured with the Progensa assay. Linear regression models were fit to identify factors that impact PCA3 score and to determine age-specific reference values. Predictive accuracies of logistic regression models predicting presence of prostate cancer (PCa) were analyzed., Results: The positive biopsy rate was 37%. In multivariable linear regression, age (P < 0.001), presence of PCa (P < 0.001), and multifocal HG-PIN (P = 0.012) were independent predictors of PCA3 score. Age showed the strongest impact on PCA3 score (T = 4.77). The upper 95% confidence interval of PCA3 score in each age category was defined as the age-specific limit. A PCA3-score over the age-specific limit (PCA3-age) was associated with an 4.17-fold increased odds of being diagnosed with PCa (P < 0.001). In multivariable logistic regression models predicting the presence of PCa, predictive accuracy of a base model (age, DRE, PSA, volume) increased from 69.6 to 75.4% (P = 0.037) by adding the continuous PCA3 score, to 73.9% (P = 0.098) with the 35 cutoff (PCA3-35) and to 77.1% (P = 0.008) with PCA3-age., Conclusions: PCA3 score increases with age, independent of PCa presence. Age-specific PCA3 score reference values are superior to PSA, continuous PCA3 score, and PCA3-35 in predicting initial pBx outcome. Therefore, an age-adjusted PCA3 score should be used for interpretation of the results.

Objective: To evaluate the efficacy and the potential use of multidetector computed tomography virtual cystoscopy (MDCT-VC) in patients with gross hematuria., Methods: A total of 32 patients underwent MDCT-VC, cystoscopy, and a cytologic examination. The slice thickness of MDCT was 1 mm. Bladder distension was done with room air. The data were converted into 3-dimensional virtual reconstructive models. The data sets were reviewed independently by 2 experienced radiologists. Tumors confined to the mucosa, infiltrating the muscularis, and transmural tumors were distinguished., Results: VC showed a sensitivity and specificity of 100%. The radiologic accuracy regarding T stage correlated in 87.5%. MDCT-VC identified 21 bladder lesions suspicious for bladder cancer in 18 patients. The histologic results showed 22 patients with bladder lesions, 18 were diagnosed with transitional cell carcinoma of the bladder, 3 had bladder endometriosis, and 1 had an infiltrating colon cancer. Four patients had concomitant carcinoma in situ lesions, which were not seen completely with MDCT-VC. However, cytology was positive in those cases. Ten patients did not have any tumor signs on VC and the subsequent conventional cystoscopy did not bring any change to the initial tumor-free diagnosis of VC., Conclusion: MDCT-VC combined with urine cytology is a good alternative to conventional cystoscopy for patients with painless gross hematuria. It should be used as a decision-making aid to identify patients who will benefit from additional cystoscopic examination. Future developments should focus on the visibility of sessile and carcinoma in situ lesions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: • To study the association between specific clinical symptoms (e.g. low libido and erectile dysfunction) and testosterone levels and age in order to define symptom-specific testosterone thresholds., Materials and Methods: • Serum samples for testosterone determination were obtained from 675 healthy men. • Participants underwent urological examination and completed the Aging Males Symptoms scale, the Beck Depression Index and the International Index of Erectile Function. Overall scores and those from individual questions from the questionnaires were evaluated. • Testosterone levels in men with symptoms were compared with those in men without symptoms. • The risks of clinical symptoms were evaluated using univariate, multiple multinomial regression analyses and Bonferroni correction., Results: • Significant associations between testosterone levels and a number of androgen deficiency symptoms were seen at testosterone levels of 13.5-14.4 nmol/L, but multiple logistic regression analysis revealed confounding effects with age. • Symptoms such as loss of libido, lack of vigour and sexual dysfunction were associated with age rather than with testosterone. • Erectile dysfunction was reported at testosterone levels between 14.65 nmol/L and 14.8 nmol/L, but was again significantly associated with age rather than testosterone levels. • The severity of symptoms significantly increased with decreasing testosterone levels using univariate analysis, but only the relationship with psychological symptoms remained significant after Bonferroni correction., Conclusion: • In aging males, androgen deficiency symptoms were reported at normal levels of testosterone, but age was an important confounder. Symptom-specific testosterone thresholds could not be defined., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Background: Data on testosterone levels of patients with prostate cancer of different grade and stage are inconsistent. We retrospectively investigated serum total testosterone of a radical prostatectomy cohort to further shed light on this problem., Patients and Methods: The preoperative level of serum total testosterone of 217 patients (mean age: 65±5.8 years) undergoing radical prostatectomy between 1989 and 2002 was analyzed for possible associations with Gleason score (≤6 vs. <7 vs. 8-10) and tumor stage (pT2 vs. pT3 vs. N+) with adjustment for age, diabetes and obesity. Patients exhibiting prostate-specific antigen (PSA) levels of >10 ng/ml and biopsy Gleason scores of ≥7 were submitted to standard lymphadenectomy., Results: The multivariate model revealed a significant effect of body mass index (BMI) (p=0.0003) and diabetes (p=0.002) on testosterone levels. Significantly lower testosterone levels were recorded in patients with nodal metastases (p<0.0001) compared to patients with non metastatic disease. No significant associations between testosterone, Gleason score and stage were found in patients with non- metastatic disease., Conclusion: Testosterone levels prior to radical prostatectomy were lower in patients with nodal involvement.

Objectives: To study the putative significance of angiotensin I-converting enzyme (ACE) in renal cell carcinoma (RCC). Recent evidence has suggested that a 287-base pair insertion (I)/deletion (D) polymorphism (rs4646994) of the angiotensin I-converting enzyme (ACE) might be associated with cancer risk and progression., Methods: The present case-control study accrued 383 subjects, including 210 with RCC and 173 age- and sex-matched healthy individuals without evidence or a history of cancer. Genomic DNA was extracted from the peripheral blood leukocytes. The ACE fragment containing the polymorphism was amplified using conventional polymerase chain reaction using specific primer pairs and subsequently genotyped using agarose gel electrophoresis., Results: Overall, a DD genotype and D allele were more frequently noted in the patients with RCC than in the controls (P = .042 and P = .045, respectively), and resulted from a greater frequency of DD and D in chromophobe RCC (P = .023 and P = .020, respectively). In contrast, the genotype and allele distribution of the controls and patients with papillary or clear cell RCC was similar. The II genotype was not observed in any patient with chromophobe RCC. On multivariate logistic regression analysis, the ACE genotype was an independent risk factor for chromophobe RCC (P = .012). Neither the ACE genotypes or alleles were associated with the tumor stage or grade., Conclusions: The results of the present study have shown for the first time that the ACE insertion/deletion gene polymorphism rs4646994 might be linked with the development of chromophobe RCC. Neither the ACE genotypes nor the alleles were associated with RCC progression., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: The prevalence of lower urinary tract symptoms (LUTS) in a representative sample of Austrian males aged 15-89 years was assessed in 2009. The results were compared with the findings of a similar study conducted in 1995., Materials and Methods: A population-based cross-sectional survey on LUTS was conducted in 2009 in Austria. A quota sample of 1,926 Austrians was selected. The sample comprised 0.03% of the population and was representative in terms of age, sex, occupational status and area of residence., Results: Some degree of LUTS is reported by 64.6% of the male population in Austria aged 15-89 years. IPSS correlates significantly with age. In all age groups storage symptoms are more prevalent than voiding symptoms. The prevalence of voiding symptoms (IPSS >0) among Austrian males is 35.5% and the prevalence of storage symptoms is 61.6%. In both groups the prevalence increases with age. Compared to 1995, the prevalence of dissatisfaction declined significantly. An extrapolated number of more than 35,000 men are 'terribly' dissatisfied with their current urinary condition., Conclusions: The prevalence of LUTS in Austria meliorated in Austria significantly between 1995 and 2009. This in part may be attributed to intensified contact of males with urologists in the past., (Copyright © 2011 S. Karger AG, Basel.)

Purpose: We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression., Materials and Methods: Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival., Results: Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016)., Conclusions: GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the association between leukocytes (polymorphonuclear granulocytes -PMNL) and semen parameters at different leukocyte concentrations., Methods: This was a retrospective clinical study at a university hospital andrology clinic. Semen samples from infertile men were analyzed for sperm morphology and motility according to seminal leukocytes (PMNL) concentration (category A: >0 to <0.25 x 10(6)/mL; category B: >0.25 to <0.5 x 10(6)/mL; category C: >0.5 to <0.75 x 10(6)/mL; category D: >0.75 to <1.0 x 10(6)/mL, category E: >1 x 10(6)/mL)., Results: The percentage of sperm with normal morphology increased significantly from category A (14%) to category D (19%) but decreased in category E to levels (14%) similar to those in category A. Motility grades a and a+b (combined) also increased from category A (12%, 20%) to category D (18.0%, 28.5%) and decreased in category E (11%, 20.5%) to levels similar to those in category A. Sperm deformities and motility grades c and d increased progressively in all categories., Summary: Leukocytes had a positive association with normal morphology and progressive motility in semen samples at a concentration of 0-1 x 10(6)/mL. The findings suggest that the association between leukocytes (PMNL) and semen quality might be concentration dependent.

Objectives: To investigate the association between androgen deficiency symptoms and sexual function, serum testosterone, and therapy in testicular cancer survivors (TCS)., Methods: A total of 83 patients treated for testicular cancer were investigated. All patients completed the International Index of Erectile Function-15 and the Aging Males Symptoms scale. Age, months of follow-up, treatment modality, and serum testosterone levels were measured. Scores for the erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction subdomains of the International Index of Erectile Function-15 were calculated., Results: Overall, almost half (47.0%) of TCS experienced clinical symptoms of androgen deficiency, 28.9% had erectile dysfunction, and 25.3% had laboratory-proven hypogonadism. TCS with clinical symptoms of androgen deficiency were significantly older (median age 45.0 vs 37.5 years, P = .001) and had a longer follow-up (median follow-up 48.0 vs 39.5 months, P = .985, respectively) than TCS without symptoms. TCS with clinical symptoms had significantly lower scores for erectile function (P = .004), orgasmic function (P = .05), sexual desire (P = .001), intercourse satisfaction (P = .005), and overall satisfaction (P = .001) than those without symptoms. The aging males' symptoms correlated significantly with erectile dysfunction (r = -0.410, P = .001). In TCS with symptoms, age (r = -0.457, P = .003), but not treatment modalities (r = 0.223, P = .173) or testosterone levels (r = 0.205, P = .210), correlated with sexual function., Conclusions: Clinical symptoms of androgen deficiency were associated with sexual problems and increasing age, but not with serum testosterone or treatment.

Purpose: AURKA is a centrosome-associated serine/threonine kinase involved in mitotic chromosomal segregation. The AURKA gene is located on chromosome 20q13, also known as HPC20 prostate cancer susceptibility locus. Therefore, we investigated in this Caucasian case-control study two single nucleotide polymorphisms (SNPs) of the AURKA gene, rs8173 located in the 3'-untranslated region (G1891C) and rs2273535 in exon 5 (Phe31Ile), and their association with prostate cancer risk., Methods: DNA was extracted from peripheral blood of 824 prostate cancer patients and 1,081 control patients with benign prostatic hyperplasia (BPH). Genotypes were determined using 5'-nuclease TaqMan assays. Multiple logistic regressions were performed to calculate odds ratios (OR) and confidence intervals (CI) and to adjust for confounders., Results: The odds ratios calculated relative to the wild-type were for the homozygous polymorphic genotypes 1.11 (95% CI = 0.70-1.76) for rs8173 and 1.32 (95% CI = 0.76-2.31) for rs2273535, respectively. Stratified analyses according to Gleason score showed also no statistically significant association for the investigated polymorphisms and prostate cancer risk., Conclusions: The two investigated SNPs in AURKA were not found to be associated with prostate cancer risk. Other common SNPs of AURKA should be investigated in further studies because of its location on a prostate cancer susceptibility locus.

Objective: To assess the correlation of erectile function (EF) and physical activity (PhA) by using standardized, validated instruments in healthy men., Methods: A urologist examined 674 men aged 45-60 yr at their place of work. That included a urological physical examination, medical history, and assessment of testosterone (T) and sex hormone-binding globulin; all men completed the 5-item International Index of Erectile Function (IIEF-5) as well as the Paffenbarger score. PhA was assessed in kilojoules per week (4.2 kJ=1 kcal)., Results: A positive correlation between the IIEF-5 and the Paffenbarger score (r=0.164, p<0.001) was found. The IIEF-5 score increased with an increasing Paffenbarger score up to a level of 4000 kcal/wk. T revealed a trend to a significant impact on the IIEF-5 score, but showed no association with the Paffenbarger score. The risk of severe erectile dysfunction (ED) was decreased by 82.9% for males with PhA of at least 3000 kcal/wk compared with males with PhA under 3000 kcal/wk (OR=0.171, p=0.018)., Conclusion: Increasing PhA from 1000 to 4000 kcal/wk may reduce the risk of ED.

Objectives: High-grade prostate cancer is associated with low serum testosterone levels, which generally recover after radical prostatectomy. The cause of this low testosterone level is unclear, and it has been hypothesized that cancer cells produce a factor that disturbs the pituitary-gonadal axis. Inhibin is a hormone that has a negative feedback effect on this axis. The aim of this study was to investigate the role of serum inhibin in patients with prostate cancer., Methods: The serum hormone levels of the pituitary-gonadal axis, including inhibin levels, in patients with prostate cancer were compared with those in patients with benign prostatic hyperplasia. Testosterone levels of less than 3 ng/mL were classified as hypogonadal. Prostate cancer was classified according to Gleason score as high grade (Gleason score 7 to 10) or low grade (Gleason score 2 to 6)., Results: A total of 196 men (126 with prostate cancer and 70 with benign prostatic hyperplasia) were entered into the study. The serum inhibin levels did not differ significantly between the patients with benign prostatic hyperplasia and those with prostate cancer (150.0 versus 131.75 pg/mL, P = 0.062), between men with hypogonadal and eugonadal disease (143.0 versus 146.5 pg/mL, P = 0.573), or between those with low-grade and high-grade cancer (151.5 versus 146.0 pg/mL, P = 0.830). Men with high-grade cancer had lower levels of serum testosterone than did those with low-grade cancer (3.49 versus 4.09 ng/mL, P = 0.056)., Conclusions: The results of our study have shown that although high-grade prostate cancer is associated with low serum testosterone levels, inhibin does not appear to be the cause of this phenomenon.

Objective: To investigate the spontaneous variation of leukocytospermia (>1 million/mL) in semen samples from infertile men., Design: Prospective cohort study., Setting: Andrologic clinic at university hospital., Patient(s): Ninety-nine men evaluating for infertility causes., Intervention(s): Two semen analyses according the World Health Organization criteria combined with urologic investigation without any treatment., Main Outcome Measure(s): Spontaneous (downward/upward) variation in leukocyte count, sperm concentration, total motility, and morphology between the two semen samples., Result(s): In the first semen analysis, 21% of men had leukocytospermia. By the second analysis, leukocyte concentrations were within the normal range in 9 of these 21 men, corresponding to a downward variation of 43%. In contrast, 7 of 78 patients with normal leukocyte levels at the first analysis had leukocytospermia at the second analysis, corresponding to an upward variation of 9%. The upward variation rates for sperm concentration, total motility, and morphology were 4%, 17%, and 4%, respectively. Downward variation rates were considerably higher for total motility and morphology (30% and 28%, respectively)., Conclusion(s): The rate for spontaneous downward variation of leukocytospermia in the absence of treatment was 43% in this study. This rate should be taken into consideration when treating infertile men with leukocytospermia, because effective medical therapy is still lacking.

Background: The introduction of PSA testing in Austria led to a steep increase of the incidence of prostate cancer. We want to present the course of the number of newly diagnosed cases of prostate cancer in Austria since 1997, and set these numbers in relation to the total of radical prostatectomies (with resection of lymph nodes) in the same time period. All numbers were retrieved from health statistics of Statistics Austria. The report period of cancer cases and of RPE comprises the years 1997-2004. All calculations were performed for totals as well as for 5-year age groups (40-89 years of age)., Findings: The number of prostate cancer cases rose from 1997 to 2004 by 35%, while the number of RPE rose by 94% in the same time period. The proportion of RPE in relation to new cases rose from 41% in 1997 to 59% in 2004., Conclusion: A slight decrease of prostate cancer mortality can already be observed in Austria, but the question of over-treatment still awaits analysis.

Objective: To assess the quality and activity of spermatogenesis in the contralateral healthy testicle at the time of orchiectomy and to assess whether any tumor-related factor such as tumor type or vascular invasion is a risk factor for impaired spermatogenesis., Design: Retrospective cohort study., Setting: University hospital., Patient(s): Seventy-six patients undergoing orchiectomy for seminoma or nonseminomatous germ cell tumor (NSGCT)., Intervention(s): Open biopsy of contralateral healthy testicle at the time of orchiectomy., Main Outcome Measure(s): Quality of spermatogenesis using median and highest Johnsen score in correlation with histopathologic tumor type, vascular invasion, and serum tumor markers and hormone levels., Result(s): Contralateral spermatogenesis is reduced in seminomas and in NSGCTs, with median Johnsen scores of 8.9 and 8.6, respectively. Similar results were seen in tumors with vascular invasion (median Johnsen score 8.8 [range 8.2-9.5]) and without vascular invasion (median Johnsen score 8.8 [range 8.1-9.2]). Areas with good-quality spermatogenesis were found in 88.9% of seminoma and 92.5% of NSGCT biopsies., Conclusion(s): Testicular cancer is associated with impaired spermatogenesis, but neither the histopathologic tumor type nor the presence of vascular invasion correlated with significantly reduced spermatogenesis.

Objective: To determine whether sex hormones alone or in combination with body mass index (BMI) influence mood in men., Subjects and Methods: Blood samples were taken from 669 manual workers (aged 43-67 years) to measure sex hormone levels, in particular bioavailable testosterone (BAT). At the same time BMI was calculated. All participants completed the Beck's Depression Inventory (BDI) for the evaluation of depression. Then BMI and BAT were correlated to the BDI scores, to determine a possible interaction., Results: There was a quadratic main effect for BAT on the BDI scores, i.e. an increased risk of depression with an odds ratio of 1.871 (P = 0.029) for hypo- and hypergonadal men. Also, there was an interaction between BAT and BMI, which was mainly detected in underweight and obese men. This U-shaped effect for underweight and obese men was not detected in men with a 'normal' weight, who had a significantly linear decrease in the risk of depression by changing from the hypogonadal to the eugonadal subgroup, as well as for changing from the eugonadal to the hypergonadal subgroup, with a mean odds ratio of 0.513 (P = 0.032)., Conclusions: Depression depends on BAT and BMI; in men of normal weight, an increase in BAT reduces the risk of depression, which is not the case in underweight and obese men. Consequently eugonadal men with normal testosterone levels have the lowest risk of depression.

Objectives: The lack of cure with medical therapy implies life-long treatment emphasising the need for a thorough understanding of the long-term outcome. We review the natural history, markers for progression, placebo effect, efficacy, pharmacoeconomic aspects, and preventive measures., Methods: Literature review with particular reference to long-term controlled studies using plant extracts, alpha1-blockers, 5alpha-reductase inhibitors (5-ARIs), and combination therapy., Results: There is a long-lasting (>or=12 mo) placebo response of symptoms (20% decrease) and maximum flow rate (10% rise). The five long-term controlled trials of plant extracts are inconclusive and therefore their role in contemporary medical management is still controversial. The alpha1-blockers provide fast amelioration of symptoms yet have no relevant impact on the risk of acute urinary retention or surgery. Combination therapy should be reserved for moderately or severely symptomatic patients with a high risk of progression; in the majority of patients the alpha1-blocker can be safely stopped after 6-12 mo. The preventive use of 5-ARIs in men with no or mild symptoms at risk of progression is scientifically sound yet not generally accepted mainly for economic reasons., Conclusions: A sharp contrast exists between the duration of the longest controlled trial (4.5 yr) and the situation in real life with treatment periods up to one or two decades of life. Real-life and registry data will be the only source of this important information in the future.

Objectives: To investigate the prevalence of hypogonadism in correlation with androgen deficiency symptoms in testicular cancer survivors., Methods: Luteinizing hormone, follicle-stimulating hormone, serum testosterone, dehydroepiandrosterone, and sex hormone binding globulin levels were determined in patients who had undergone treatment for unilateral testicular cancer. Patients with serum testosterone levels less than 3.0 ng/mL were classified as hypogonadal; all other testosterone levels signified eugonadism. Additionally, all patients completed the Aging Males' Symptoms scale: scores of less than 26 indicated no androgen deficiency symptoms and scores greater than 27 indicated symptoms., Results: According to testosterone level, 18 (26.5%) of 68 patients were hypogonadal and 50 (73.5%) were eugonadal (P = 0.456). According to the Aging Males' Symptoms scale, 23 (33.8%) of the 68 patients had androgen deficiency symptoms and 45 (66.2%) had no symptoms (P = 0.267). The median testosterone level was 3.6 ng/mL in all patients with androgen deficiency symptoms, 2.4 ng/mL in patients with androgen deficiency symptoms who were hypogonadal, and 4.7 ng/mL in those with androgen deficiency symptoms who were eugonadal., Conclusions: Testicular cancer survivors are at risk of developing hypogonadism and androgen deficiency symptoms. However, no specific testosterone threshold could be detected at which symptoms start, indicating that each patient has an individual testosterone threshold for androgen deficiency symptoms.

Objective: To investigate the correlation between leukocytospermia, bacteriospermia, and clinical signs of infection and to evaluate antiinflammatory therapy., Design: Prospective nonrandomized study., Setting: Andrologic clinic at university hospital., Patient(s): A total of 56 patients were evaluated, and 12 of them received further treatment with a Cox-2 inhibitor., Intervention(s): Semen analysis and clinical investigation were done according to World Health Organization guidelines. Serum levels of leukocytes, C-reactive protein (CRP), and prostate-specific antigen (PSA) were measured from blood samples., Main Outcome Measure(s): Sperm concentration, leukocyte concentration, serum leukocyte count, CRP, PSA, bacterial growth., Result(s): Leukocytospermia (>1 x 10(6)/mL) was present in 60.7% of the semen samples, significant pathogenic bacterial growth was detectable in 35.7%, and 14.3% of the samples fulfilled the criteria for ejaculate signs of infection. All serum parameters were within the normal range. In abacterial leukocytospermia, treatment with a Cox-2 inhibitor decreased leukocytospermia from 5.5 x 10(6)/mL to 1.0 x 10(6)/mL (P=.001) and increased sperm concentration from 22.5 x 10(6)/mL to 48.0 x 10(6)/mL (P=.02)., Conclusion(s): There was no evidence of an immune response in the peripheral blood system. In abacterial leukocytospermia, treatment with a Cox-2 inhibitor seems to be able to reduce leukocytospermia and increase sperm count.

Objectives: To report the long-term results in 7 patients (including the 5-year results in 3 patients) after high-intensity focused ultrasonography (HIFU) combined with irradiation to treat testicular tumors in a solitary testis., Methods: Transcutaneous HIFU ablation of testicular tumors is based on a technique using a piezoceramic transducer operating at 4.0 MHz with a site intensity of 1600 to 2000 W/cm2. In a Phase II trial, 7 patients with the typical sonographic pattern of a tumor in a solitary testis were treated with transcutaneous HIFU, as a minimally invasive organ-preserving approach, followed 6 weeks later by prophylactic testicular irradiation (range 18 to 20 Gy). The aim was to ablate the entire cancer in a single therapeutic HIFU session. In all 7 patients, the contralateral testis had previously been removed because of testicular cancer., Results: One patient received two cycles of chemotherapy for a single suspicious retroperitoneal lymph node diagnosed 6 months after HIFU. The other 6 protocol-treated patients remained tumor free at a mean follow-up of 42 months (range 3 to 93). One patient, who had refused postoperative irradiation, developed a recurrent tumor within 6 months. No patient showed any signs of clinical hypogonadism, and the International Index of Erectile Function score was normal for all patients. No androgen substitution was necessary. The only adverse effect noted was a small thermal lesion of the scrotum in 1 patient., Conclusions: Despite the lack of tumor histologic examination, transcutaneous HIFU followed by irradiation permits a minimally invasive, organ-preserving, curative treatment for tumors in a solitary testis.

Objectives: To investigate the correlation between the presence of white blood cells (WBC) without the use of specific stain to differentiate leukocytes and the presence of bacteria in semen samples of infertile men., Methods: A total of 143 semen samples of men who attended an andrologic clinic for the evaluation of fertility were investigated using routine semen analysis (according to WHO laboratory guidelines) and bacterial culture., Results: WBC were found in 43.4% (62/143). There were no WBC in 56.6% (81/143) of the samples (group I) while WBC were found in 43.4% (62/143) of the samples (group II). Pathogenic bacteria were detected in 48.2% (39/81) in group I and in 54.9% (34/62) in group II, all in all Bacteriospermia was present in 51.1% (73/143). The most common bacteria were Ureaplasma urealyticum, Enterococcus faecalis and Escherichia coli (23.8%, 16.8%, and 7.0% of samples, respectively). The sensitivity/specificity for detecting bacteria was 0.47/0.60 at a cut-off level of 0.25 Mio/mL WBC and 0.16/0.84 at a cut-off level of WBC 1 Mio/mL, representing likelihood ratios of 1.16 and 1.04, respectively. The greatest ratio between sensitivity and specificity (0.37/0.72) was found at a cut-off level of 0.5 Mio/mL WBC, with a likelihood ratio of 1.29., Conclusions: Counting WBC instead of a specific stain for the detection of leukocytes has only a poor sensitivity/specificity for the detection of bacteria.

Objective: To investigate semen quality in infertile men from an urban population over an 18-year period., Design: Retrospective study., Setting: Andrology clinic at a city university hospital., Patients: A total of 9,327 men were referred to the clinic for infertility investigation. After excluding those with azoospermia, 7,780 samples were evaluated., Intervention(s): Semen samples were analyzed within half an hour of production using computer-automated semen analysis and phase microscopy., Main Outcome Measure(s): Sperm concentration, morphology, and motility; semen pH and leukocyte concentration; and patient age., Result(s): The median patient age over the study period was 31.6 years, with an increase from 30.8 years in 1986 to 34.4 years in 2003. The median sperm concentration was 10.25 million/mL for the entire period, with a decline from 27.75 million/mL in 1986 to 4.60 million/mL in 2003. The median proportion of normally shaped spermatozoa was 15%, and the proportion of motile spermatozoa was 21%. The pH increased from 7.4 in 1986 to 7.9 in 2003, and the median leukocyte concentration was 1.50 million/mL., Conclusion(s): A constant decline in median sperm concentration was found in the infertile men. The reason for this remains unclear, although the high pH and leukocyte concentration indicates the involvement of infection.

Objective: The aim of this study was to evaluate the association between serum levels of testosterone and free testosterone to lifestyle in aging males., Methods: Men between 45 and 85 years were assessed regarding body mass index (BMI), nicotine and alcohol consumption, stress level, physical and social activity, and sleeping quality by a self-administered questionnaire. In parallel, serum levels of testosterone (T), free testosterone (fT), LH, FSH, DHEA-S, E2 and SHBG were obtained., Results: In total, 375 men with a mean age of 59.9 years (9.2 +/- SD) entered this study; 25.4% and 27.4% had hypogonadal testosterone or free testosterone serum levels, respectively. Nicotine consumption (smokers had higher levels of T and fT; p < 0.01), BMI (negative correlation to T; p < 0.01) and age (negative correlation to fT; p < 0.001) correlated with serum levels of testosterone or free testosterone. Physical and social activity, nicotine and alcohol consumption, stress level and sleep quality did not show a significant association with serum androgen levels., Conclusion: This prospective study of 375 men aged 45 to 85 years confirms the correlation between age, BMI and smoking with serum levels of testosterone and free testosterone, whereas the investigated variety of lifestyle factors did not show a significant association to serum androgen levels.

Objectives: To investigate the influence of treatment for testicular cancer on the pituitary-gonadal axis and sexual function in long-time survivors after unilateral orchiectomy., Methods: Blood was drawn from patients treated for testicular cancer during routine oncologic follow-up for measurement of luteinizing hormone, follicle-stimulating hormone, sexual hormone-binding globulin, testosterone, and bioavailable testosterone. Sexual function was evaluated using the International Index of Erectile Function 15-item (IIEF-15) questionnaire. Patients were grouped according to treatment: group 1 followed a surveillance strategy, group 2 received two cycles of carboplatin monotherapy, and group 3 underwent cisplatin, etoposide, and bleomycin chemotherapy., Results: No statistically significant difference was found in the serum hormonal levels among the three groups, and all hormonal levels were within the 95% confidence range, except for follicle-stimulating hormone. The median serum testosterone level was 3.5 ng/mL in group 1, 3.9 ng/mL in group 2, and 4.2 ng/mL in group 3. In group 1, the median IIEF-15 score was 64.0, and the median Erectile Function (EF) domain score was 28. The median scores in groups 2 and 3 were 62.5 for IIEF-15 and 27.5 for EF and 65.0 for IIEF-15 and 30.0 for EF, respectively. No correlation was found between testosterone level and IIEF-15 or EF score., Conclusions: None of the treatments investigated had a significant influence on the serum hormonal levels in long-time survivors of testicular cancer. Patients undergoing chemotherapy have no greater risk of developing a hormonal disorder than those following a surveillance strategy, and therapy for testicular cancer is not a risk factor for erectile dysfunction.

Purpose: Erectile dysfunction (ED) may be associated with low serum total testosterone (T), low serum bioavailable testosterone (BAT) and high body mass index (BMI) in aging men., Materials and Methods: A total of 675 workers (age range 45 to 60 years old) were entered into this study. Investigations were performed directly at their place of work. Exclusion criteria were abnormal urogenital status, antihypertensive drugs, medication possibly affecting the endocrine function and a history of previous pelvic trauma. T and sex hormone-binding globulin were measured with commercially available assays, and BAT was calculated from T and sex hormone-binding globulin. BMI was assessed and every individual completed a self-administrated questionnaire for erectile function (International Index of Erectile Function [IIEF-5])., Results: T and BAT showed a significantly negative correlation with age and BMI. Each additional year of increase in age caused a decrease in the IIEF-5 score of 0.195 (p <0.001). Increase in BMI by 1 kg/m reduced IIEF-5 by 0.141, independent of age (p =0.005). Multiple logistic regression analyses confirmed the influence of increased age and higher BMI on the risk of ED. The corresponding odds ratio for ED was 1.082 (p <0.001) and 1.076 (p <0.001), respectively. These data indicate an increase in ED risk by 8.2% per year and by 7.6% per kg/m BMI. Severe cases of ED (IIEF-5 score 7 or less) were significantly associated with a decrease in T and BAT. Individuals with low BAT (1 ng/ml or less) had a 3 times higher risk of severe ED compared with men with BAT greater than 1 ng/ml (odds ratio 3.045, 95% CI 1.088 to 8.522, p =0.034). The result of the multiple logistic regression analysis was adjusted to age and BMI, and did not show a significant influence on the incidence of severe ED., Conclusions: BMI contributes strongly to ED. Low T or BAT are only relevant if IIEF-5 questionnaire results in severe ED.

Objectives: To examine the impact of polymorphism in the androgen-responsive element I region of the prostate-specific antigen (PSA) gene on the serum testosterone level and Gleason score in patients with newly diagnosed, untreated prostate cancer (PCa). High-grade PCa is associated with a low serum testosterone level, and the testosterone level has been negatively correlated with the expression of PSA., Methods: Endocrine factors (including testosterone, follicle-stimulating hormone, and luteotropic hormone), PSA level, prostate volume, and Gleason score were measured in 134 patients with untreated, biopsy-verified PCa. PSA polymorphism was determined by polymerase chain reaction-based methods using DNA from peripheral blood samples., Results: Patients with the PSA G/G genotype had lower serum testosterone levels (3.5 +/- 1.2 ng/mL) than those with the A/A genotype (4.3 +/- 1.6 ng/mL) or the A/G genotype (4.4 +/- 1.5 ng/mL). The PSA level in the A/A and A/G genotype groups were significantly lower than that in the G/G genotype group (18.2 +/- 55.0 ng/mL versus 20.5 +/- 27.6 ng/mL, P = 0.013). In a multiple logistic regression model, the odds ratio for the G/G polymorphism was significantly increased for Gleason score (odds ratio 2.4, 95% confidence interval 1.6 to 10.4; P = 0.02) and serum testosterone level (odds ratio 0.44, 95% confidence interval 0.36 to 0.94; P = 0.01) relative to genotypes A/A and A/G., Conclusions: Our results showed that the PSA G/G genotype is associated with a greater Gleason score and serum PSA level but lower serum testosterone level and could be considered a risk factor for a poor outcome of PCa.

For decades, plant extracts have been amongst to the most popular drugs for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE). Only a few of the many published studies meet the criteria of the WHO-BPH consensus conference. The few placebo-controlled, long-term (>/=6 months) studies suggest a positive effect of some extracts (saw palmetto, beta-sitosterol, urtica, rye-grass, saw palmetto/urtica combination) on LUTS; an effect on uroflow, post-void residual volume, prostate volume and PSA was not consistently demonstrable. Randomised trials against an active comparator (alpha1-blocker, 5alpha-reductase inhibitors) are difficult to interpret. Due to the lack of prospective studies, several meta-analyses have been published that can not, however, replace prospective studies. None of the BPH-guidelines currently recommend plant extracts, yet universally conclude that this is an interesting approach. Further prospective studies using WHO standards are required to reliably determine the role of such extracts in the management of elderly men with LUTS due to BPH/BPE.

Objective: To analyse long-term rates of reoperation, myocardial infarction and mortality after transurethral (TURP) and open prostatectomy (open PE) in a nation-wide analysis., Material and Methods: Patients who underwent TURP (n=20,671) or open PE (n=2452) in Austria between 1992 and 1996 entered this study and were followed for up to 8 years. Actuarial cumulative incidences of reoperation (TURP, urethrotomy, bladder neck incision), myocardial infarction and death after 1, 5 and 8 years were calculated. Data were provided by the Austrian Health Institute (OBIG)., Results: Actuarial cumulative incidences of a secondary TURP after primary TURP at 1, 5 and 8 years were 2.9%, 5.8% and 7.4%; the respective numbers after open PE 1.0%, 2.7% and 3.4%. The overall incidence of a secondary endourological procedure (TURP, urethrotomy, bladder neck incision) within 8 years was 14.7% after TURP and 9.5% after open PE. The 8 years incidence of myocardial infarction was identical after TURP (4.8%) and open PE (4.9%). In parallel, mortality rates at 90 days (TURP: 0.7%; open PE: 0.9%), one year (2.8% vs. 2.7%), 5 years (12.7% vs. 11.8%) and 8 years (20% vs. 20.9%) was identical after TURP and open PE., Conclusions: This large-scale, contemporary, nation-wide analysis confirms the higher reoperation rate after TURP compared to open PE. We observed no excess risk of myocardial infarction or death after TURP compared to open PE.

Microsomal epoxide hydrolase (mEH) plays a dual role in the detoxification and activation of tobacco procarcinogens. Two polymorphisms affecting enzyme activity have been described in the exons 3 and 4 of the mEH gene, which result in the substitution of amino acids histidine to tyrosine at residue 113, and arginine to histidine at residue 139, respectively. We performed a hospital-based case-control study consisting of 277 newly diagnosed lung cancer patients and 496 control subjects to investigate a possible association between these two polymorphisms and lung cancer risk. The polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism and TaqMan assay using DNA from peripheral white blood cells. Logistic regression was performed to calculate odds ratios (ORs), confidence limits (CL) and to control for possible confounders. The exon 3 polymorphism of the mEH gene was associated with a significantly decreased risk of lung cancer. The adjusted OR, calculated relative to subjects with the Tyr113/Tyr113 wild type, for the His113/His113 genotype was 0.38 (95% CL 0.20-0.75). An analysis according to histological subtypes revealed a statistically significant association for adenocarcinomas; the adjusted OR for the His113/His113 genotype was 0.40 (95% CL 0.17-0.94). In contrast, no relationship between the exon 4 polymorphism and lung cancer risk was found. The adjusted OR, calculated relative to the His139/His139 wild type, was for the Arg139/Arg139 genotype 1.83 (0.76-4.44). Our results support the hypothesis that genetically reduced mEH activity may be protective against lung cancer.

Background: Previous studies on immunoreactive androgen levels in serum have revealed equivocal associations with the risk of prostate cancer (CaP). The aim of this study was to compare serum biological androgen activity between men with newly diagnosed CaP and age-matched men with benign prostatic hyperplasia (BPH)., Methods: Caucasian men with newly diagnosed, untreated CaP (n = 101) and age-matched patients with BPH (n = 103) were investigated. Serum androgen bioactivity (ABA) levels were measured using a recently developed recombinant cell bioassay., Results: In comparison to men with BPH, CaP patients with Gleason score >or=8 (n = 16) had lower serum ABA (P < 0.05), and patients with Gleason score or=8 (P = 0.07) displayed suppressed ABA levels in relation to serum testosterone. As the entire group, men with CaP (n = 101) had significantly lower serum ABA than age-matched men with BPH (n = 103): median 3.0 nM (range, 0.8-6.4 nM) versus 3.2 nM (range, 0.8-7.9 nM) testosterone equivalents, respectively (P < 0.005). By contrast, serum immunoreactive testosterone and SHBG concentrations and free androgen indices did not differ significantly between the two groups., Conclusions: Patients with CaP have lower serum ABA than controls with BPH, and men with low or high Gleason score display suppressed circulating ABA-to-testosterone ratio. These features may reflect interaction between variables such as the degree of tumor differentiation and tumor volume with androgen metabolism., (Copyright 2003 Wiley-Liss, Inc.)

Objectives: To assess the natural history of lower urinary tract symptoms (LUTS) in a cohort of previously untreated men over five years., Methods: Men participating in a health-screening project completed the International Prostate Symptom Score (IPSS) in 1996. In 2001, men older than 45 years with no prostate surgery or LUTS-specific medication before 1996 completed the IPSS plus a questionnaire on several aspects of LUTS. At the same time, all men underwent a health examination in 1996 and 2001., Results: A total 456 men aged 52+/-12 years (range: 40-84) at baseline completed the 5-year follow-up. Mean IPSS increased from 4.6 to 5.5 (+20%; p<0.0001) and the IPSS-Ql from 0.8 to 1.1 (+38%; p<0.0001) over five years. Progression of IPSS and IPSS-Ql were highly correlated. No change of IPSS was reported by 19%, a worsening by 50% and an improvement by 31%. Not all aspects of LUTS progressed in a similar pattern, storage symptoms had a higher tendency to improve over time. Medical therapy was initiated in 7%, 39% and 67% of those with mild, moderate or severe LUTS at baseline, respectively. In a multivariate analysis age and degree of being bothered by LUTS were independent predictors for initiation of therapy., Conclusions: This 5-year longitudinal study of men without previous LUTS treatment demonstrates the slow nature of the disease's progression. Not all aspects of LUTS progress in a similar pattern. Initiation of therapy is influenced by patient age and by the degree of being bothered by LUTS.

Purpose: We investigate potential associations of serum testosterone with microvessel density, androgen receptor expression and AR gene polymorphism in men with untreated prostate cancer., Material and Methods: Serum luteinizing hormone, follicle-stimulating hormone, estradiol and testosterone were determined in men with newly diagnosed prostate cancer. The number of tumor vessels per 0.46 mm. and androgen receptor density (as the percent positive nuclei) were quantified immunohistochemically on prostate cancer areas of prostate biopsy specimens. Polymorphisms within the AR gene (number of CAG repeats) were determined by polymerase chain reaction and restriction fragment length polymorphism analysis using DNA from peripheral blood., Results: The 39 men entered into this study were grouped into 16 with low (3 ng./ml. or less, group 1) and 23 with normal (greater than 3 ng./ml., group 2) serum testosterone. Mean prostate specific antigen +/- SD was significantly lower in group 1 than in group 2 (18.8 +/- 11.1 versus 27.2 +/- 12.2 ng./ml., p = 0.03). Mean Gleason score (7.4 +/- 1.3 versus 6.0 +/- 1.2, p = 0.01), androgen receptor density (96.6% +/- 2.8% versus 84.8% +/- 7.2%, p = 0.03) and tumor vessel density (63.0 +/- 30.8/0.46 versus 39.0 +/- 22.9/0.46 mm.2, p = 0.007) were significantly higher in group 1 than in group 2. The number of CAG repeats within the AR gene did not correlation with serum androgen., Conclusions: Low serum testosterone in men with newly diagnosed prostate cancer is associated with higher tumor microvessel and androgen receptor density as well as with higher Gleason score, suggesting enhanced malignant potential.

Objectives: To investigate the impact of health status on androgen levels in men and to assess the age-related changes in androgen levels., Methods: Sera were obtained from 526 men (age 20 to 89 years) participating in a health screening project and 35 men selected according to the SENIEUR protocol, which excludes those with underlying disease. The health screening project participants were divided into two groups: healthy men (n = 133; group 1) and the remainder (n = 393; group 2). The total testosterone and sex hormone-binding globulin levels were quantified, and the amount of free testosterone (cfT) was calculated., Results: The lowest annual declines in androgen level were observed in group 3 (testosterone 0.2%; cfT 0.4%), followed by group 1 (testosterone 0.4%; cfT 0.8%) and group 2 (testosterone 0.8%; cfT 0.9%). Body mass index and levels of cholesterol, triglycerides, and glucose correlated negatively (P <0.01) with testosterone and cfT. Decade-adjusted reference values (mean +/- 2 standard deviations) for testosterone and cfT were defined. The proposed lower testosterone reference value declined gradually from 3.1 ng/mL (20 to 29 years) to 1.7 ng/mL (70 years or older)., Conclusions: In this cross-sectional study, serum androgens declined in aging men, and the extent of this decrease correlated with health status. A fixed, non-age-adjusted reference value does not adequately reflect this and might lead to a false diagnosis of androgen deficiency, particularly in elderly men. The clinical value of age-related reference values, however, needs to be determined in prospective studies.

Objectives: A number of interactions between age-related changes in serum levels of dehydroepiandrostendione sulfate (DHEA-S) and estradiol and symptoms of aging men have been proposed, yet data regarding this issue are scant. We therefore set up a prospective study to analyze these associations., Methods: In a prospective, cross-sectional study, men aged 45-85 years were recruited. All men completed a questionnaire containing 38 items covering a number of aspects of the aging male. Questionnaires were compiled by using items from previously published and validated questionnaires. Several socioeconomic parameters were also determined. In parallel, serum levels of testosterone, free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), DHEA-S, estradiol, sex hormone binding globulin and prostate-specific antigen (PSA) were quantified by commercially available immunoassays., Results: A total of 375 men with a mean age of 59.9 +/- 9.2 years (mean +/- standard deviation) were analyzed. Average DHEA-S and estradiol levels of 135.8 +/- 90.9 micrograms/dl and 29.7 +/- 14.6 pg/ml, respectively, were recorded. DHEA-S serum levels were negatively correlated to patient age, sexual function score, total score and PSA. Estradiol serum levels were positively correlated to testosterone and free testosterone. None of the other scores or questions revealed a correlation with DHEA-S or estradiol serum levels., Conclusion: This prospective study elucidates only small interactions between partial androgen deficiency of the aging male (PADAM)-related symptoms and serum levels of DHEA-S and estradiol. Nevertheless, the data suggest an impact of DHEA-S on sexual function.