Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907).

PURPOSE: This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. METHODS AND MATERIALS: This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. RESULTS: Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P = .65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P = .62) and 1.2 versus 0.6% (P = .62), respectively. CONCLUSIONS: Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results.

The correlation between erectile function and adiponectin levels in men with late-onset hypogonadism.

Aim: This study investigated the relationship between erectile dysfunction (ED) and adiponectin levels in hypogonadal men.Methods: In this study, 218 patients with hypogonadism (mean age: 65.1 ± 8.3 years) were enrolled. All patients underwent physical examinations, with measurement of body mass index, body fat ratio, and waist circumference. The erectile function was assessed using the sexual health inventory for men (SHIM) scoring system. Blood biochemical profiles such as free testosterone, fasting blood glucose, and lipid profile including adiponectin levels were measured. All patients were divided into two groups based on their SHIM score: normal to moderate ED (SHIM score ≥ 12) and severe ED (SHIM score < 12), and the factors associated with severe ED were determined. Patients with severe ED were divided into two groups based on adiponectin levels (cutoff value of 7.0 µg/mL), and their basic characteristics were compared between these two groups.Results: The severe ED group was older and had higher adiponectin levels. In patients with severe ED, various metabolic parameters were significantly worse in the low adiponectin groups than in the non-low adiponectin group.Conclusions: The risk of developing cardiovascular diseases is extremely high in hypogonadal men with severe ED who had lower serum adiponectin levels.

Risk Factors Affecting Decreased Libido Among Middle-Aged to Elderly Men; Nocturnal Voiding is an Independent Risk Factor of Decreased Libido.

INTRODUCTION: Decreased libido in middle-aged and elderly men is often difficult to treat, and identifying the risk factors affecting decreased libido is important for the clinical management of decreased libido. However, limited information is available regarding specific risk factors in this population. AIM: The present study investigated the risk factors for decreased libido among middle-aged and elderly men. METHODS: Patients who attended our male andropausal outpatient clinic between 2009 and 2015 were enrolled. All patients completed a self-administered questionnaire, which included the Aging Male Symptoms (AMS) scale, International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM). Information on waist size, body mass index, present illness, present use of any medication, and lifestyle habits were collected by each attending physician. Blood biochemical data such as free testosterone, total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-Chol), and hemoglobin A1c values were assessed. Libido was assessed based on AMS scale question 17, and a score of 4 or higher was defined as severely decreased libido (severe group). MAIN OUTCOME MEASURE: The clinical factors associated with severely decreased libido were analyzed based on multiple regression analysis. RESULTS: A total of 292 subjects were included in the analysis, 111 (38%) of which belonged to the severe group. The mean age of study subjects was 66.2 years, and the mean FT value was 7.1 ± 2.2. Comparisons of each variable among the severe and not severe groups showed significant differences in older age, current cigarette smoking, AMS scale, IPSS, frequency of nocturnal voiding, SHIM score, and HDL-Chol value. Multivariate regression analysis revealed that current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for severely decreased libido. Furthermore, the frequency of nocturnal voiding significantly increased with severity of decreased libido. CONCLUSION: Current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for a severely low libido. K Shigehara, Y Kato, M Iijima, et al. Risk Factors Affecting Decreased Libido Among Middle-Aged to Elderly Men; Nocturnal Voiding is an Independent Risk Factor of Decreased Libido. Sex Med 2021;9:100426.

Low free testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors.

Aim: We investigated whether low plasma free testosterone (FT) levels could predict cardiovascular events (CVE) in Japanese men with coronary risk factors.Methods: Male patients with classical coronary risk factors who had undergone serum FT testing were enrolled. New incidences of CVE were retrospectively investigated among all eligible participants based on their medical records.Results: Overall, 466 male outpatients with coronary risk factors without a previous history of CVE were identified. Throughout the follow-up period (median = 92 months), 126 CVE occurred. The Kaplan-Meier survival analysis according to the tertiles of plasma FT levels revealed that patients with the lowest FT tertile (<6.5 pg/mL) had a higher likelihood of developing CVE than those with the highest tertile (>9.3 pg/mL) (p<.01). Multivariate analysis showed that increased frequency of CVE was observed with lower FT tertiles, independent of other coronary risk factors, with hazard ratios of 0.617 (95% CI, 0.389-0.976; p=.030) and 0.524 (95% CI, 0.309-0.887; p=.016) for the second and highest tertile relative to the lowest FT tertile, respectively.Conclusion: Among Japanese men with coronary risk factors, a lower FT level was a predictor for the development of cardiovascular diseases independent of other coronary risk factors and age.

The five-year effects of testosterone replacement therapy on lipid profile and glucose tolerance among hypogonadal men in Japan: a case control study.

Objective: This study investigated the efficacy of 5-year testosterone replacement therapy (TRT) on lipid profile and glucose tolerance in Japanese hypogonadal men.Methods: Fourteen patients, who received continuous TRT for 5 years, and 22 controls with 5-year observations were enrolled. The patients in the TRT group had received intramuscular injections of testosterone enanthate (250 mg) every month for 5 years. We collected the following data: blood pressure, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), total cholesterol, triglyceride (TG), high density lipoprotein-Chol values, and prostate specific antigen (PSA) level at baseline, 1-, 3-, and 5-years from initial intervention. These data were compared between the two groups.Results: There were no statistically significant differences in any other baseline characteristic, excluding SBP, between the two groups. FBS was significantly improved at 3- and 5-year visits in the TRT group compared to the control group. Furthermore, the HbA1c level and TG value demonstrated a significant decrease at 1-, 3-, and 5-years in the TRT group. However, no significant difference in changes to PSA levels from baseline in both groups was observed.Conclusions: Five-year TRT could improve FBS, HbA1c, and TG levels among Japanese hypogonadal men with no significant increase in PSA.

Report of the third Asian Prostate Cancer study meeting.

The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP-specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future.

Effect of testosterone replacement therapy on sexual function and glycemic control among hypogonadal men with type 2 diabetes mellitus.

We investigated the effect of testosterone replacement therapy (TRT) on glycemic control and sexual function among hypogonadal men with type 2 diabetes mellitus (T2DM). From the EARTH study, 86 patients (47 in the TRT and 39 in the non-TRT groups) with a diagnosis of T2DM were extracted. We collected data on waist circumference, body mass index, body fat volume, free testosterone, hemoglobin (Hb), fasting blood sugar, and hemoglobin A1c (HbA1c) at baseline and after 12 months. Aging Male Symptoms (AMS) score and International Prostate Symptom Score were obtained. Sexual function was assessed by questions 15 (sexual ability), 16 (morning erections), and 17 (sexual desire) of AMS subscores. The TRT group received intramuscular testosterone enanthate (250 mg) injections every 4 weeks for 12 months. Body fat percentage, Hb, and HbA1c were significantly improved in the TRT group. In addition, sexual ability and frequency, and sexual desire showed a significant improvement in the TRT group after 1 year TRT. On the other hand, any parameters including glycemic control and sexual functions were not significantly improved in non-TRT groups. One-year TRT can improve sexual function and glycemic control among hypogonadal men with T2DM.

NCCN Asia Consensus Statement prostate cancer.

The National Comprehensive Cancer Network, an NPO organization comprised of university hospitals and cancer centers in the US. The publication of clinical practice guidelines on the treatment, diagnosis, prevention and screening is one of important activities. Background factors of prostate cancer patients, such as the prevalence, age at the diagnosis and mortality are markedly different between Western countries and Asia. Thus, various factors should be taken into consideration at the treatment choice for individual patients. Experts from Asian countries were published as the Asia Consensus Statement. In this review, we explain important points of the Asia Consensus Statement such as differences in the epidemiological backgrounds of patients, differences in treatment options and differences in medical insurance systems.

Combined androgen blockade achieved better oncological outcome in androgen deprivation therapy for prostate cancer: Analysis of community-based multi-institutional database across Japan using propensity score matching.

BACKGROUND: This study investigated how differences in the method of the first-line androgen deprivation therapy (ADT) affected the time to castration-resistant prostate cancer. METHODS: The Japan Study Group of Prostate Cancer compiled a nationwide community-based database on prostate cancer patients who underwent ADT. That database included 13 774 patients who were started on ADT by surgical or medical castration alone (monotherapy group, 5395 cases) or ADT in combination with a nonsteroidal anti-androgen (combined androgen blockade (CAB) group, 8379 cases). We used logistic regression analysis with background factors as independent factors to calculate propensity scores in regard to selection of CAB. Next, for 8826 cases of propensity score-matched patients, we compared the survival rates in the two groups. RESULTS: The CAB group showed a significantly better progression-free survival (PFS) rate (65.6% vs 59.6% at 5 years; median time to progression, 11.6 vs 7.1 years; hazard ratio in the CAB group: 0.78, with a 95% confidence interval of 0.72 to 0.84; P < 0.001). In subgroup analysis based on the background factors, the PFS rate was generally better in the CAB group in all risk subgroups except for those having significant risk factors. CONCLUSION: Propensity score matching analysis revealed the prolongation of PFS by CAB in prostate cancer patients without significant risk factors. It would possible to decide the type of the first-line ADT according to the prostate cancer risk.

Background factors and short-term health-related quality of life in patients who initially underwent radical prostatectomy or androgen deprivation therapy for localized prostate cancer in a Japanese prospective observational study (J-CaP Innovative Study-1).

BACKGROUND: This prospective observational study elucidated the usefulness of hormonal therapy for localized prostate cancer. Background factors and the health-related quality of life in patients who initially underwent radical prostatectomy (RP) or primary androgen deprivation therapy (PADT) for localized prostate cancer are summarized. MATERIALS AND METHODS: Patients aged 67-76 years with clinical stage T1c or T2 localized prostate cancer treated with PADT or RP, a prostate-specific antigen concentration of <20 ng/mL, and Gleason score of ≤7 were included. Health-related quality of life results estimated by the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite (EPIC) were investigated. RESULTS: In total, 850 patients who underwent RP and 370 patients who underwent PADT were enrolled. The proportion of patients with comorbidities of hypertension, cardiovascular disease, and/or cerebrovascular disease was greater in the PADT group than in the RP group. The proportion of patients deciding on treatment was significantly higher in the PADT group than in the RP group. In the RP group, the scores of many SF-8 and EPIC domains decreased at 3 months following surgery and returned to baseline levels at 1 year. In the PADT group, several domains gradually decreased during the year after treatment initiation. The proportion of patients with decreased satisfaction scores at 1 year compared with baseline was lower in the PADT group than that in the RP group. CONCLUSION: Treatment risk influenced decisions on primary treatment for localized prostate cancer. Although there was a selection bias, short-term overall satisfaction in the PADT group was superior to that in the RP group in this clinical study.

Sleep disturbance as a clinical sign for severe hypogonadism: efficacy of testosterone replacement therapy on sleep disturbance among hypogonadal men without obstructive sleep apnea.

OBJECTIVE: The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea. METHODS: Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12 months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17). RESULTS: We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12 months. CONCLUSION: Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.

Association of TUSC1 and DPF3 gene polymorphisms with male infertility.

PURPOSE: Recently, genome-wide association studies of a Hutterite population in the USA revealed that five single nucleotide polymorphisms (SNPs) with a significant association with sperm quality and/or function in ethnically diverse men from Chicago were significantly correlated with family size. Of these, three SNPs (rs7867029, rs7174015, and rs12870438) were found to be significantly associated with the risk of azoospermia and/or oligozoospermia in a Japanese population. In this study, we investigated whether the rs10966811 (located in an intergenic region between the TUSC1 and IZUMO3 genes) and rs10129954 (located in the DPF3 gene) SNPs, previously related to family size, are associated with male infertility. In addition, we performed association analysis between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility. METHODS: We genotyped 145 patients with infertility (including 83 patients with azoospermia and 62 with oligozoospermia) and 713 fertile controls by PCR-RFLP technique for polymorphism. Because rs10966811 has no restriction sites, the SNP rs12376894 with strong linkage disequilibrium was selected as an alternative to rs10966811. RESULTS: There was a statistically significant association between rs12376894 proxy SNP of rs10966811 and oligozoospermia. Also, a statistically significant association between rs10129954 and azoospermia, and oligozoospermia was observed. When we assessed the relationship between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility traits, we found that rs12348 in TUSC1 was significantly associated with azoospermia and oligozoospermia, but rs2772579 in IZUMO3 was not associated with male infertility. CONCLUSION: We found that the polymorphisms in TUSC1 and DPF3 displayed strong associations with male infertility.

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): a study protocol for a multicenter randomized phase III trial.

BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. METHODS/DESIGN: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. DISCUSSION: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014.

Metanephric adenoma treated with laparoscopic nephrectomy: A case report.

Metanephric adenoma is an uncommon benign renal tumor that occurs predominantly in adult females and rarely in children. Its histomorphology resembles that of epithelial Wilms' tumor and papillary renal cell carcinoma. From a diagnostic and therapeutic perspective, recognition of this entity is important as it has a more favorable clinical outcome compared with Wilms' tumor and renal cell carcinoma. Metanephric adenoma should not be treated with nephrectomy if the tumor size is small. However, preoperative diagnosis of this disease is extremely challenging. The present study describes a case of this rare disease, which was treated with laparoscopic nephrectomy. The tumor was not clearly enhanced in the early phase on contrast-enhanced computed tomography imaging. The immunohistochemical analysis revealed positive immunoreactivity for vimentin and Wilms' tumor 1, and partial positivity for cytokeratin (CK) AE1/AE3, CK56, and CK34, consistent with metanephric adenoma. Although metanephric adenoma is difficult to diagnose preoperatively, this rare disease must be considered in order to avoid unnecessary surgical procedures in these patients.

Report of the Second Asian Prostate Cancer (A-CaP) Study Meeting.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world.

Human papillomavirus prevalence in the anus and urine among HIV-infected Japanese men who have sex with men.

BACKGROUND: The present study investigated human papillomavirus (HPV) prevalence in anal and urine samples, and evaluated cytological findings among human immunodeficiency virus (HIV)-infected Japanese men who have sex with men (MSM). METHODS: A total of 148 patients were enrolled. Anal and urine samples were collected from each participant, and a HPV-DNA test and genotyping were performed using flow-through hybridization. In addition, anal cytology was evaluated based on Papanicolaou staining. Questionnaires regarding lifestyle habits and sexual behavior were obtained. RESULTS: The ß-globin gene was positive in 131 (88.5%) anal samples and 139 (94.0%) urine samples. Among the ß-globin-positive samples, the HPV prevalence in anal and urine samples was 80.9% and 30.9%, respectively. High-risk HPV (HR-HPV) was detected in 57.3% of anal samples and 20.9% of urine samples. Among 122 adequate cytological samples, anal cytological abnormalities were observed in 99 cases (81.1%). Anal cytological tests revealed that atypical squamous cells of an undetermined significance (ASCUS) were detected in 57 (46.7%) patients, followed by low-grade squamous intraepithelial lesions (SIL) in 35 (28.7%), high-grade SIL in five (4.1%), and atypical squamous cells cannot exclude high-grade SIL (ASC-H) in two (1.6%), respectively. The nadir counts of CD4-positive T-lymphocyte less than 200 µL and anal HR-HPV infection were independent risk factors for anal cytological atypia over ASC-H. CONCLUSIONS: The present study demonstrated high HPV prevalence in the anus and urine, and showed a high incidence of anal cytological atypia associated with HR-HPV infections among HIV-infected MSM patients.

Single-nucleotide polymorphisms in the human RAD21L gene may be a genetic risk factor for Japanese patients with azoospermia caused by meiotic arrest and Sertoli cell-only syndrome.

Genetic mechanisms are implicated in some cases of male infertility. Recently, it was demonstrated that male mice lacking the gene for RAD21L exhibited azoospermia caused by meiotic arrest. Mouse RAD21L is a functionally relevant meiotic α-kleisin that is essential for male fertility. Therefore, we hypothesized that RAD21L mutations or polymorphisms may be associated with male infertility, especially azoospermia secondary to meiotic arrest. To determine if RAD21L defects are associated with azoospermia in groups of patients with meiotic arrest, we performed direct sequencing of the RAD21L coding regions in 38 Japanese patients with meiotic arrest and in 200 normal controls. Three coding single-nucleotide polymorphisms (SNP1-SNP3) were detected in the meiotic arrest patient group. Sertoli cell-only syndrome is considered a common cause of non-obstructive azoospermia. For comparison, the RAD21L coding regions in which SNP1-SNP3 were detected were sequenced in 140 patients with Sertoli cell-only syndrome. Statistical analyses were used to compare the two groups of patients with the control group. Genotype and allele frequencies of SNP2 and SNP3 were notably higher in the two patient groups compared with the control group (Bonferroni adjusted p value <0.016). These results suggest a critical role for RAD21L in human spermatogenesis.

Testosterone Deficiency and Nocturia: A Review.

Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS), and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT) is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions.

Effects of testosterone replacement therapy on hypogonadal men with osteopenia or osteoporosis: a subanalysis of a prospective randomized controlled study in Japan (EARTH study).

OBJECTIVE: We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis. METHODS: From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n = 35) and control (n = 34) groups. The TRT group was administered 250 mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated. RESULTS: At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0 ± 5.0 vs. 3.0 ± 3.2; p = .0434) and in adiponectin value (-0.90 ± 3.33 vs. 0.10 ± 2.04; p = .0192). There were no significant changes in other parameters. CONCLUSIONS: TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.

Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22-CCR4 axis.

Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues. In vitro co-culture of prostate cancer cells and macrophages resulted in increased CCL2 and CCR2 levels in prostate cancer cells. The addition of CCL2 induced CCL22 and CCR4 production in prostate cancer cells. The migration and invasion of prostate cancer cells via enhanced phosphorylation of Akt were promoted by CCL17 and CCL22. CCR4 may be a potential candidate for molecular-targeted therapy.