Kenta Sumii

Improved Lower Urinary Tract Symptoms Associated With Testosterone Replacement Therapy in Japanese Men With Late-Onset Hypogonadism

This study aimed to investigate the effects of testosterone replacement therapy (TRT) on lower urinary tract symptoms (LUTS) in men with late-onset hypogonadism (LOH) and to identify parameters predicting the efficacy of TRT in improving LUTS. This study included 60 consecutive Japanese men who were diagnosed with LOH and subsequently received TRT between January 2009 and December 2014. In this series, 250 mg of testosterone was injected intramuscularly every 3 or 4 weeks in all patients. The following parameters were retrospectively reviewed: body mass index (BMI), Aging Male Symptom (AMS) score, International Prostate Symptom Score (IPSS), International Index of Erectile Function–5 (IIEF-5) score, residual urine volume, prostate volume, serum levels of the prostate-specific antigen (PSA), and total- and free-testosterone levels before and 6 months after TRT. No significant differences were observed in BMI, residual urine volume, or prostate volume between surveys before and after TRT. The AMS score, IPSS, and IIEF-5 score were significantly improved and significant increases were noted in the serum levels of PSA and total- and free-testosterone levels after TRT. An analysis of IPSS subscores documented the significant improvement in storage symptom scores, but not in voiding symptom scores after TRT. Multivariate analyses of parameters assessed in this study identified the pretreatment AMS score, posttreatment IIEF-5 score, and prostate volume as independent predictors of improvements in IPSS following TRT. This study revealed that TRT appeared to have considerable therapeutic effects on LUTS, particularly on storage symptoms, in men with LOH.

Erectile function and its impact on quality of life in Japanese men on hemodialysis

Abstract The objective of this study was to characterize the erectile function and its impact on health-related quality of life (HRQOL) in Japanese men on hemodialysis. This study included 65 consecutive Japanese men <80 years on hemodialysis. Erectile function and HRQOL were evaluated using the Sexual Health Inventory for Men (SHIM) and the Short-Form 8 (SF-8) survey, respectively. These 65 men were classified into 54 with SHIM ≤11; relatively severe erectile dysfunction (ED) (group A) and 11 with SHIM ≥12; relatively mild ED (group B). There were significant differences in age, marital status, ankle-brachial index (ABI), and serum levels of free testosterone and prolactin between groups A and B. Of several factors examined, age, marital status and ABI were significantly associated with the severity of ED on univariate analysis, and of these 3 factors, only age was significantly associated with severity of ED on multivariate analysis. SF-8 survey revealed that all scale scores in group A were inferior to those in group B. Comparatively severe ED appeared to be frequently observed in Japanese men on hemodialysis, and this trend was marked in elderly men. Furthermore, the severity of ED had a negative impact on the wide range of HRQOL in these men.

Prospective assessment of health-related quality of life in men with late-onset hypogonadism who received testosterone replacement therapy

The objective of this study was to characterise the status of health‐related quality of life (HRQOL) in Japanese men with late‐onset hypogonadism (LOH) treated with testosterone replacement therapy (TRT). HRQOL in 69 consecutive Japanese men with LOH undergoing TRT for at least 6 months was prospectively evaluated before and 6 months after the initiation of TRT using the Medical Outcomes Study 8‐Item Short‐Form Health Survey (SF‐8). All eight‐scale scores except for bodily pain (BP) in the 69 patients at 6 months after the introduction of TRT significantly improved compared with those before TRT; however, all scale scores except for BP in the 69 patients were significantly inferior to those in age‐matched Japanese controls irrespective of the timing of SF‐8. Multivariate analyses of several parameters revealed that both age and Aging Male Symptom (AMS) score had an independent impact on mental health (MH), despite the lack of an independent association between any score and the remaining factors examined. TRT appeared to significantly improve the status of HRQOL in men with LOH; however, even after the introduction of TRT, HRQOL associated with MH remained significantly impaired in elderly men and/or those with a high AMS score.

Dutasteride-mediated morphological changes in the genitourinary tract associated with altered expression patterns of the androgen and estrogen receptors in male rats

We evaluated the effects of dutasteride on the genitourinary tract using fifteen 8‐week‐old male Sprague–Dawley rats. Animals were divided into three groups comprising five animals each and treated as follows. Group A was a control group, members of Group B received oral administration of dutasteride 0.1 mg/kg/day from the age of 8 to 16 weeks, and members of Group C were castrated at the age of 8 weeks. All rats were killed at the age of 16 weeks for the sample collection of blood, bladder, prostate, seminal vesicles, and penis. Then, we evaluated the pathological examination for evaluating the tissue fibrosis and hormonal receptor expression. The results showed that the mean size of the prostate and seminal vesicles was smaller in Group B and Group C than in Group A. Serum and tissue concentrations of both testosterone and dihydrotestosterone were remarkably reduced in serum and all tissues in Group C compared with Group A. On the other hand, in Group B, only dihydrotestosterone was reduced in serum and penis. Histopathological examination revealed that Group C showed statistically significant histological changes, such as an increase in fibrotic tissue in the bladder, prostate, and penis. Similarly, Group B showed fibrotic changes in the prostate and penis compared with the Group A. Immunofluorescent staining revealed that the androgen receptor was more strongly expressed than the estrogen receptor beta in Group A. On the other hand, in Group C, weak expression of the androgen receptor and strong expression of the estrogen receptor beta was noted. In Group B, these changes were noted in the prostate and penis. These findings suggest that dutasteride cause morphological changes not only in prostate but also in penis. These changes are associated with altered expression patterns of androgen receptor and estrogen receptor.

MP60-02 MOLECULAR CHANGES INDUCED BY MIRABEGRON IN RAT SERTOLI CELL PRIMARY CULTURE

RESULTS: Four weeks after subcutaneous autograft of LSCs in combination with Sertoli and myoid cells in castrate mice, the cells in graft expressed 3B-HSD, SOX-9 and A-SMA. Serum testosterone in castrated mice that received autograft was significantly higher compared to mice that did not receive autograft (22.4þ/-1.9 VS 11.9þ/0.8 Ng/DL, p<0.05). Importantly, mice that received LSC autograft maintained production of LH and FSH with levels higher than mice that received testosterone pellet implant (LH 3.09þ/-1.47 VS 0.01þ/-0.01 ng/ml) (FSH 102.6þ/-28.1 VS 51.7þ/-7.4ng/ml) respectively. Furthermore, T levels consistently increased at 15, 30 and 60 days following subcutaneous autograft (12.01þ/-0.87ng/DL (neg CTL) vs 15.1þ/1.50ng/DL (15 days Autograft) vs 22.26þ/-1.33ng/DL (30 days Autograft) vs 37.3þ/-9.6ng/DL (60 days Autograft)), demonstrating differentiating LSC within the autograft. In addition, we found that levels of 3BHSD were induced upon SAG (DHH inducer) treatment in-vitro conditions. Immunostaining autografts (4 weeks), containing LSCs treated with SAG before subcutaneous implantation, showed higher levels of SOX9, and ASMA. Importantly, T levels were significantly higher (p<0.05) in mice received SAG treated autografts vs negative controls (23.95þ/4.11 Ng/DL vs 11.91þ/-0.80 Ng/DL). Collectively these results establish that Hedgehog signalling induces survival of adjacent testicular cells and regulates graft function. CONCLUSIONS: Our results demonstrate that subcutaneous autograft of LSC in combination with Sertoli cells and myoid cells can increase serum testosterone without inhibiting circulating LH and FSH in castrate mice. Extratesticular LSC appear to be regulated by Hedgehog signalling. Leydig stem cell autograft can a novel therapeutic approach to increase serum testosterone while simultaneously preserving hypothalamic-pituitary-gonadal axis. Factors involved in hedgehog signalling can be utilized to enhance graft efficacy.

PD33-10 HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED TESTOSTERONE-PRODUCING LEYDIG CELLS AMELIORATE SERUM TESTOSTERONE LEVEL IN RATS.

METHODS: We used a cryptorchid rat testes model of SSC disturbance. The model was generated using intra-abdominal injection of flutamide (7.5 mg/rat) into pregnant Sprague-Dawley rats. Normal testes, unilateral undescended testes (UDT), and contralateral descended testes (DT) were extirpated on postnatal day 9, when two types of SSCs (gonocytes and spermatogonia) co-existed and gonocytes began differentiation into spematogonia. A microarray examining DT and UDT focused on miR-135a, which exhibited lower expression in UDT. In situ hybridization (ISH) was used for the detection of the localization of miR-135a and quantitative polymerase chain reaction (qPCR) to determine the organ specificity of the gene. We then searched the miR-135a target genes using a computer program, followed by the luciferase assay to demonstrate the suppression effect of miR-135a in vitro. RESULTS: qPCR revealed that miR-135a was 8.3e21.3 times over-expressed in the testes than in other organs; ISH showed miR135a localized in SSCs. In silico analysis identified FOXO1 as a putative target gene of miR-135a. FOXO1 has a sequence complementary to miR-135a’s seed sequence at its 3’ untranslated region. FOXO1 localized in SSCs, and a luciferase assay demonstrated that miR-135a directly suppressed FOXO1 expression in mouse GC-1 cells. CONCLUSIONS: We demonstrated that miR-135a is associated with the maintenance of SSCs and that its putative target gene is FOXO1. Because FOXO1 is already proven necessary for maintenance of SSCs and we proved that SSCs are reduced in UDT, we hypothesized that miR-135a was lowered to facilitate the active FOXO1 expression, leading to SSC maintenance. Thus, miR-135a is associated with SSC maintenance through regulation of FOXO1 expression.

MP86-11 PROSPECTIVE ASSESSMENT OF PSYCHOLOGICAL SYMPTOMS IN MEN WITH LATE-ONSET HYPOGONADISM WHO RECEIVED TESTOSTERONE REPLACEMENT THERAPY

validation of FLOW vs AUA-SS, and perform a critical analysis of the AUA-SS via validated literacy and numeracy scales. METHODS: A total of 161 men were recruited from clinics at Nashville General Hospital, a safety net hospital in Nashville, TN. We collected demographic data and assessed literacy/numeracy using validated tools: the revised Rapid Estimate of Adult Literacy in Medicine (REALM-R), the Brief Health Literacy Screen (BHLS), and the Subjective Numeracy Scale (SNS). Patients were administered the FLOW questionnaire and the AUA-SS. We evaluated the completion rates, completion times, and whether or not patients required assistance to complete either questionnaire. RESULTS: Median age was 56 years, 99 men (61.5%) identified as Black/African American, and the median REALM-R score was six. There was a significant correlation between FLOW scores and AUA-SS (r1⁄40.63, p<0.001). Among men with adequate health literacy (REALM-R 6-8; n 1⁄487), all were able to complete the FLOW and AUASS; however, among men with low literacy (REALM-R <6; n 1⁄474) all were able to complete the FLOW but only 81% were able to complete the AUA-SS (p<0.001). For the FLOW, health literacy was unrelated to median completion time (21.5 sec), the median number of prompts needed (0), or median score (2). For the AUA-SS, although the median number of prompts needed to complete the questionnaire (2) and median AUA-SS score (10.5) did not differ as a function of the men’s health literacy, men with low health literacy who completed it had a median completion time of 129.5 seconds compared to 92 seconds for those with adequate health literacy (p<0.001). CONCLUSIONS: The FLOW questionnaire meets criterion validity due to its strong, significant correlation with the AUA-SS for those who were able to complete both measures. However, a critical analysis of the AUA-SS utilizing valid health literacy and numeracy scales reveals the AUA-SS is frequently not completed, required prompting, and/or took longer to complete for men with low health literacy. Further studies of the FLOW questionnaire in a larger cohort in diverse clinical settings are needed.