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.

The association between leukocytes and sperm quality is concentration dependent.

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.

Androgen deficiency symptoms in testicular cancer survivors are associated with sexual problems but not with serum testosterone or therapy.

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.

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.

Serum inhibin--not a cause of low testosterone levels in hypogonadal prostate cancer?

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.

Spontaneous variation of leukocytospermia in asymptomatic infertile males.

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.

Effect of leukocytospermia on fertilization and pregnancy rates of artificial reproductive technologies.

The aim of this study was to investigate the fertilization and pregnancy rates of artificial reproductive technologies using semen samples without (<1 x 10(6)/mL) and with (> or =1 x 10(6)/mL) leukocytospermia. The overall fertilization rate was 63.4% (range, 44.4-87.5%) in nonleukocytospermic couples and 64.3% (range, 45.3-100.0%) in leukocytospermic couples, whereas the corresponding pregnancy rates were 34.5% and 50%, respectively. These results show that leukocytospermia may not necessarily have a negative effect on outcome after either in vitro fertilization or intracytoplasmic sperm injection.

Does histopathologic tumor type or vascular invasion influence spermatogenesis in testicular cancer?

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.

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.

Hypogonadism and androgen deficiency symptoms in testicular cancer survivors.

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.

The changing distribution of pT stage in testicular germ cell tumours from 1976 to 2005: a single-centre analysis of histopathological reports.

OBJECTIVE: To assess the changing distribution of stage in seminoma and nonseminomatous germ cell tumours (NSGCTs), as recent reports contained no detailed information on pT stage and vascular invasion, important factors in the decision for further treatment. PATIENTS AND METHODS: Histopathological reports from 1976 to 2005, from patients who had surgery for testicular tumours at the authors' institution, were investigated with special focus on pT stage and its distribution. The whole study period was divided into six 5-year periods. The incidence of seminoma was compared with NSGCT, defined according to the Tumour-Nodes-Metastasis (TNM) classification. RESULTS: In each 5-year period the median number of tumours treated surgically was 86; the distribution of seminomas and NSGCTs remained stable during the study period (P = 0.201). pT4 and pT3 tumours declined or disappeared in both histopathological groups, while pT2 and pT1 tumours increased during the study period. Since 1996-2000, pT1 tumours decreased, whereas pT2 tumours increased in seminomas (P = 0.085) and NSGCTs (P = 0.003). CONCLUSION: The incidence of seminoma and NSGCT has not changed over the last 30 years in Vienna. With the establishment of vascular invasion in the TNM classification in 1997, the incidence of pT1 decreased while that of pT2 increased. Since then, the incidence of pT1 tumours in seminomas was 45.8% and 29.1% in NSGCT. According to generally accepted treatment guidelines, these patients might need no adjuvant treatment after surgery.

Correlation of leukocytospermia with clinical infection and the positive effect of antiinflammatory treatment on semen quality.

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.