Lower urinary tract symptoms and its potential relation with late-onset hypogonadism

The study of the health status of the aging male takes presently a more integrative approach and it appears that ailments typical of male aging, such as lower urinary tract symptoms (LUTS), (visceral) obesity, metabolic syndrome and erectile failure are significantly interrelated. A common denominator of the above ailments is lower-than-normal testosterone levels occurring in a significant proportion of elderly men. This review addresses the potential connections between LUTS and late-onset hypogonadism. In animal studies there appear to be androgen and estrogen receptors in the urothelium and smooth muscle cells of the urethra and bladder of the rat and rabbit, as well as in the neurons in the autonomic ganglia of the prostatic plexus of the male rat. Upon castration electrically evoked relaxations of the smooth muscle of the prostatic urethra were decreased. There is a Rho-kinase activation/endothelin pathway; possibly involved in the increased smooth muscle activity found in both LUTS/benign prostate hyperplasia. Nitric oxide (NO) appears to have a smooth muscle relaxing effect in the urogenital organs. Studies in humans have convincingly shown that phosphodiestererase inhibitors have a beneficial effect on LUTS. More intervention studies should be undertaken to test the clinical validity of the theoretically plausible interrelationship between LUTS and late-onset hypogonadism.     

Prostate-specific antigen decline pattern in advanced prostate cancer receiving androgen deprivation therapy and relationship with prostate-specific antigen progression

Introduction: The aim of this study is to evaluate prostate-specific antigen decline pattern including prostate-specific antigen kinetics following androgen deprivation therapy on prostate-specific antigen progression in the patients with advanced prostate cancer.

Materials and methods: Ninety-seven advanced prostate cancer patients receiving maximum androgen deprivation therapy were enrolled in case–control study. Baseline prostate-specific antigen, Gleason Score, bone metastase, nadir prostate-specific antigen, time to nadir prostate-specific antigen, declining slope to nadir prostate-specific antigen, estimated baseline prostate-specific antigen half-time, current prostate-specific antigen, post-nadir prostate-specific antigen time, estimated prostate-specific antigen, estimated decline of baseline prostate-specific antigen as quantitative, and ratio were recorded and calculated.

Results: The ratio of prostate-specific antigen progression was significantly lower at the patients who had slower declining slope to prostate-specific antigen, longer time to nadir prostate-specific antigen, and lower estimated decline ratio of baseline prostate-specific antigen (p: .016, p: .020, and p: .026, respectively).

Conclusions: The shorter time to nadir prostate-specific antigen following androgen deprivation therapy, faster declining slope to nadir prostate-specific antigen and higher estimated decline ratio of baseline prostate-specific antigen are associated with higher risk of disease progression in patients with hormone-sensitive prostate cancer.     

The relationship between circulating testosterone and inflammatory cytokines in men

Testosterone is the predominant gonadal androgen in men. Low testosterone levels are found to be associated with an increased in metabolic risk and systematic inflammation. Since adipose tissue is a source of inflammatory cytokines, testosterone may regulate inflammation by acting on adipose tissue. This review aimed to explore the role of testosterone in inflammation and its mechanism of action. Both animal studies and human studies showed that (1) testosterone deficiency was associated with an increase in pro-inflammatory cytokines; (2) testosterone substitution reduced pro-inflammatory cytokines. The suppression of inflammation by testosterone were observed in patients with coronary artery disease, prostate cancer and diabetes mellitus through the increase in anti-inflammatory cytokines (IL-10) and the decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Despite these, some studies also reported a non-significant relationship. In conclusion, testosterone may possess anti-inflammatory properties but its magnitude is debatable. More evidence is needed to validate the use of testosterone as a marker and in the management of chronic inflammatory diseases.     

Symptomatic change in Japanese hypogonadal patients several years after androgen replacement therapy

Objective.?There are few reports on the prognosis of patients receiving androgen replacement therapy (ART). In this study, we evaluated the subsequent symptoms of Japanese hypogonadal patients who had received ART, within several years previously by mail-in survey.

Methods.?Thirty-three aged men with symptoms of hypogonadism and testosterone deficiency who had received ART for 6 months responded to this survey. The survey consisted of questions associated with present physical and mental status and desire to resume ART. The Aging male’s symptoms (AMS) scale, IIEF-5 and SF-36 were also evaluated at pre-initiation, termination of ART and the time of the survey.

Results.?The mean duration from the last treatment was 55 months. Compared with the treatment period, more than half of patients (57.5%) answered that their present condition was better. Scores on the AMS scale, IIEF and SF-36 were all improved significantly in the early stages of treatment and not worsened a long period of time after ART was discontinued.

Conclusions.?For symptomatic Japanese hypogonadal patients, subjective effects of treatment were observed during the early treatment period and remained unchanged after discontinuation of ART. A short treatment period may thus be adequate in Japanese hypogonadal patients as regards symptomatic changes.     

Association of testicular p63 expression and spermatogenesis in androgen receptor knockout (ARKO) mice

Objective.?To study changes of testicular p63 expression and its effect on spermatogenic function in seminiferous tubules in androgen receptor knockout (ARKO) mice.

Methods.?A total of 28 ARKO mice (ARKO group) screened by Cre-lox and 28 male Wistar mice without ARKO (controlled group) were enrolled in our study. Route pathology was performed and p63 examination was detected by immunohistochemistry in testes. Linear correlations were used to explore potential associations between p63 protein expression and spermatogenic function (TMS score).

Results.?In ARKO group, inner diameter of seminiferous tubules was decreased (62?±?1.3?μm vs. 91?±?1.2?μm), thickness of the basal membrane of the tubules (4?±?0.3?μm vs. 2.7?±?0.5?μm), cellular population within tubules was reduced (2?±?0.4 vs. 4?±?0.1 layers), degree of spermatogenesis within the tubules turned to disturbance (3?±?1.0 vs. 5?±?0.1), Testicular Makler score was lower than controlled group (7?±?0.2 vs.15?±?0.3), they had significant differences (p <0.01). P63 expressed significantly lower in ARKO group than that in Wistar group, and was limited at stages from spermatocyte to round spermatid. (Percentage of positive cells ? 68.1?±?3.7 vs. 81.7?±?5.1, p?<0.001). The HSCORE yielded similar results (HSCORE 3.7?±?0.3 vs. 2.0?±?0.2, p?<0.001). p63 protein expression was significantly positively correlated with spermatogenic function (r?=?0.87, p?<0.01).

Conclusions.?p63 developed important effect on spermatogenesis and the regulatory effect of p63 on spermatogenesis mainly occurred in the early stage of spermiogenesis in testis.     

Relationship between testosterone serum levels and lifestyle in aging men

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.     

Correlation between sex hormone levels and obesity in the elderly male

Objective: To investigate the levels of sex hormones and androgen receptor (AR) in elderly male patients and to explore a possible correlation with obesity. Methods: The cross-sectional study included 314 Elderly males (age ≥ 65 year). Of these subjects, 104 were healthy (age range 65–92 year; mean 71.38 ± 5.154 year), 74 were obese (65–87 year; 71.32 ± 4.74 year), and 111 were overweight (65–85 year; 71.43 ± 5.03 year). The following parameters were measured: total testosterone (TT), free testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), estradiol (E2), luteinizing hormone, follicle-stimulating hormone and AR. Results: (i) The levels of TT and SHBG in the obesity group were significantly lower than those in non-obese subjects. (ii) Body mass index (BMI) negatively correlated with TT and SHBG. (iii) Multiple regression analysis revealed that TT (β: ?0.230; p = 0.045) and SHBG (β: ?0.163; p = 0.02) were statistically correlated with BMI. Conclusion: Testosterone levels in the obese population were significantly lower than in the non-obese population and there is a significant association between testosterone levels and the extent of obesity.     

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

Purpose.?We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH).

Methods.?Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250?mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment.

Results.?Forty-six patients (ART group, n?=?23; control, n?=?23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7?±?8.7 vs. 12.5?±?9.5; p?<?0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p?<?0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p?<?0.05), whereas no significant changes were seen in the controls.

Conclusion.?ART improved LUTS in hypogonadal men with mild BPH.