Immunohistochemical expression analysis of Cx43, Cx26, c-KIT and PlAP in contralateral testis biopsies of patients with non-seminomatous testicular germ cell tumor.

Non seminomatous testicular germ cell tumors (NSTGCTs) express fetal stem cell markers and display dysregulation of connexin 43 expression. Persistence of fetal spermatogonial characteristics was implicated in the emergence of testicular germ cell tumors. The objective of this study was to analyze the tubular architecture in contralateral testes of patients with NSTGCT. We studied morphologic alterations, expression patterns of markers for the integrity of the germinal epithelium (gap junction proteins connexin 43 and 26), as well as of the embryonic markers c-KIT and placental alkaline phosphatase (PlAP), both established markers to detect carcinoma in situ (CIS). In all samples, tubules showing maturation of germ cells up to spermatozoa were observed. In addition, tubules with alterations in tubular architecture and with impaired spermatogenesis occurred. In tubules showing aberrant spermatogenesis, connexin 43 (Cx43) signal was down-regulated and a shift of signal from gap junctions to the cytoplasm occurred. Concomitantly, Cx26 was found highly up-regulated in tubules with incomplete and aberrant germ cell maturation. All testes exhibited single spermatogonia with positive reaction for c-KIT and a significant positive correlation was found between the mean number of c-KIT positive spermatogonia per tubule and the percentage of tubules presenting severely impaired spermatogenesis. Our data show alterations of the normal architecture of the germinal epithelium and disturbances of spermatogenesis in the contralateral testes of patients with NSTGCT in all cases evaluated. The concomitant occurrence of c-KIT positive spermatogonia and defects in tubular architecture is in line with the hypothesis that patients with NSTGCT suffer from disturbed germ cell development.

Are there symptom-specific testosterone thresholds in aging men?

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.

Lower serum total testosterone is associated with lymph node metastases in a radical prostatectomy cohort study.

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.

PSA testing in Austria: induced morbidity and saved mortality.

Opportunistic screening of healthy men by prostate-specific antigen (PSA) testing led to a steep increase of prostate cancer incidence in Austria. The objective of this study was to quantify how many additional men are diagnosed with prostate cancer by PSA testing, to save one man from prostate cancer death. Regression models for incidence and mortality for the time periods 1983-1991 and 1992-2003 by age groups 50-59 and 60-69 years were estimated. For 1992-2003, expected numbers of incidence and mortality were calculated. The first estimates for the years 1992-2003 were calculated using the regression model including the years 1983-1991. The second estimates were also calculated using the regression model, but including only the years 1992-2003. The difference between estimates was then summed up for 1992-2003. The corresponding sums of incidence and mortality were compared to provide estimates for the effect of the introduction of PSA screening on incidence/mortality ratio. According to our calculation for the time period 1992-2003, in age group 50-69 years, a total of 512 expected prostate cancer deaths were prevented because of opportunistic PSA screening, whereas PSA testing identified a total of 9648 additional men with asymptomatic prostate cancer. In conclusion, to save one man in the age group 50-69 years in the time period 1992-2003 from prostate cancer death by PSA testing, a total of 18.8 men with asymptomatic prostate cancer had to be identified. Although this study probably underestimates the benefit (reduced mortality) and overestimates excess incidence of prostate cancer, it is far from sure that in all of these additionally identified men prostate cancer would ever have surfaced as a clinical disease, if not screened for.

How much physical activity is needed to maintain erectile function? Results of the Androx Vienna Municipality Study.

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.

Mood changes, body mass index and bioavailable testosterone in healthy men: results of the Androx Vienna Municipality Study.

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.

The impact of age, body mass index and testosterone on 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.