Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Therapeutic efficacy and safety of a free-standing motorized ejaculation aid for patients with intravaginal ejaculatory dysfunction.

Purpose: There are no approved drugs or devices for the treatment of intravaginal ejaculation disorders, and treatment is often difficult. This study aimed to evaluate the efficacy and safety of the A10 Cyclone SA + PLUS® ejaculation aid (Rends Co., Ltd., Chiba, Japan), which allows the user to adjust the intensity of stimulation, for intravaginal ejaculation disorders. Methods: Each participant was instructed to perform practice masturbation with the A10 Cyclone SA + PLUS to simulate vaginal ejaculation. After 8 weeks of training, the participants were asked about their intravaginal ejaculation status. Sexual function was also evaluated before and after the training using several specific questionnaires, including the numerical rating scale for ejaculatory satisfaction. Results: Among the 10 participants (41.5 ± 3.21 years) who completed the training and questionnaire evaluation, four (40%) became capable of intravaginal ejaculation. The questionnaire evaluation showed predominant improvement after training in the ejaculation-capable group according to the numerical rating scale, which expresses satisfaction with ejaculation. The participants experienced no significant adverse events. Conclusion: As no effective treatment currently exists for intravaginal ejaculation disorders, we conclude that the A10 Cyclone SA + PLUS may be one treatment tool for intravaginal ejaculation disorders with good efficacy and no adverse events.

Efficacy of testosterone replacement treatment for patients with symptoms of late-onset hypogonadism based on real-world patient satisfaction.

Late-onset hypogonadism is generally treated with testosterone replacement treatment. However, the efficacy rate of treatment for patients with low testosterone is not clear because patients without low testosterone are also treated in real-world clinical settings. This study comprised 110 men with low testosterone concentration of <3.0 ng/mL who underwent testosterone replacement treatment. Physical factors, laboratory and endocrinologic profiles, and scores of several questionnaires were assessed. Testosterone replacement treatment was performed with intramuscular injection of 250 mg of testosterone esters every 2-4 weeks, and efficacy was judged by patient satisfaction. After confirming efficacy, changes in several factors by the treatment were evaluated. Finally, the comparison between evaluation by patient satisfaction and by that with the questionnaires was assessed. Among the 110 patients, 77 (70.0%) were satisfied with the treatment, which was effective in 65.7%, 71.4%, and 73.1% of patients with mental, physical, and sexual dysfunction, respectively. The questionnaire scores including the Aging Males Symptoms rating scale were significantly improved in both the satisfaction and non-satisfaction group. However, no significant differences in the amount of change in questionnaire scores were found for all questionnaire scores improved by testosterone replacement treatment between the groups. Patient satisfaction was not associated with improvement of the Aging Males Symptoms score. Although testosterone replacement treatment was effective for 70.0% of the hypogonadal patients, patient satisfaction did not correlate with improvement of questionnaire scores. We concluded that not only questionnaire results but also patient satisfaction is important when evaluating efficacy in patients undergoing testosterone replacement treatment.

Circadian Rhythm of Voided Volume, Maximum Flow Rate, and Voiding Time Evaluated by Toilet Uroflowmetry in Hospitalized Women With Nocturia.

OBJECTIVE: To clarify the circadian rhythm of urination in hospitalized women with nocturia measured by toilet uroflowmetry and its age-related change. METHODS: We evaluated 2602 urinations of 58 female patients (age, 68.4 ± 15.2 years) who were hospitalized in our institution for urological disease. We assessed voided volume (VV) as averages of every hour by generalized linear mixed models with an identity link function to adjust for personal bias and age. Maximum flow rate and voiding time were analyzed by the same method after adjustment for age, personal bias, and VV. We also compared these circadian rhythms between women <70 and ≥70 years. RESULTS: VVs in the nighttime were significantly higher than that from 06:00-07:00 (205.6 ± 11.7 ml). Maximum flow rates in the afternoon were significantly higher than that from 06:00-07:00 (18.8 ± 0.93 ml/sec). Voiding time showed no statistically significant difference between the values at any time of day and that from 06:00-07:00. We also showed that the circadian rhythm of VV becomes less clear in the elderly women (P interaction = .0057). However, no significant difference was found in the maximum flow rate and voiding time regarding the pattern of the circadian rhythm between women <70 and ≥70 years old. CONCLUSION: The present study clearly showed a circadian rhythm of VV and maximum flow rate in hospitalized women with nocturia. In addition, the pattern of the circadian rhythm of VV was attenuated in women ≥70 years old.

Bone scan index (BSI) scoring by using bone scintigraphy and circulating tumor cells (CTCs): predictive factors for enzalutamide effectiveness in patients with castration-resistant prostate cancer and bone metastases.

Reports of Bone Scan Index (BSI) calculations as imaging biomarkers to predict survival in patients with metastatic castration-resistant prostate cancer (mCRPC) have been mainly from retrospective studies. To evaluate the effectiveness of enzalutamide (ENZ) in Japanese patients with mCRPC and bone metastases using BSI (bone scintigraphy) and circulating tumor cell (CTC) analysis. Prospective, single-arm study at Juntendo University affiliated hospitals, Japan. Patients were administered 160 mg ENZ daily, with 3 monthly assessments: BSI, prostate specific antigen (PSA), CTC and androgen receptor splicing variant-7 (AR-V7) status. Primary endpoint: BSI-decreasing rate after ENZ treatment. Secondary endpoints: PSA-decreasing rate and progression free survival (PFS). Statistical analyses included the Wilcoxon t-test, Cox proportional hazard regression analysis, and log-rank test. Median observation period: 17.9 months, and median PFS: 13.8 (2.0-43.9) months (n = 90 patients). A decrease in BSI compared to baseline as best BSI change on ENZ treatment was evident in 69% patients at the end of the observation period (29% patients showed a complete response, BSI 0.00). At 3 months 67% patients showed a ≥ 50% PSA reduction, and 70% after ENZ treatment. PSA decline (3 months) significantly associated with a prolonged median PFS: 18.0 (estimated) versus 6.4 months (HR 2.977 [95% CI 1.53-5.78], p = 0.001). Best BSI decline response significantly associated with a prolonged PFS: 18.1(estimated) versus 7.8 months (HR 2.045 [95% CI: 1.07-3.90], p = 0.029). CTC negative status (n = 20) significantly associated with a prolonged PFS: 13.4 [estimated] vs 8.6 months (HR 2.366, 95% CI 0.97-5.71, p = 0.041). CTC positive/AR-V7 positive status significantly associated with a shorter PFS: 5.9 months (HR 8.56, 95% CI 2.40-30.43, p = 0.0087). -reduction (3 months) and BSI-reduction (on ENZ treatment) were significant response biomarkers, and a negative CTC status was a predictive factor for ENZ efficacy in patients with mCRPC.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

The Men's Training Cup Keep Training: a masturbation aid improves intravaginal ejaculatory latency time and Erection Hardness Score in patients who are unable to delay ejaculation.

Introduction: Premature ejaculation (PE) has negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. In Japan, no oral drugs or devices are approved or used clinically to treat PE. The Men's Training Cup Keep Training (MTCK), a masturbation aid, was developed for PE. MTCK offers 5 grades of tightness and strength. Aim: We aimed to investigate the efficacy of the MTCK in patients who are unable to delay ejaculation. Methods: Inclusion criteria were 20- to 60-year-old men feeling distressed and frustrated by PE and who had the same sexual partners throughout the study period. Exclusion criteria were neurologic disease and uncontrolled diabetes mellitus, as well as the use of antidepressants, α-blockers, and 5α-reductase inhibitors. The protocol comprised an 8-week training period with the MTCK from level 1 to level 5, with each level used twice before moving to the next level. Outcome Measures: The main outcome measure was the extension of intravaginal ejaculation latency time (IELT). The secondary outcome measures were score improvements on the Premature Ejaculation Diagnostic Tool, Sexual Health Inventory for Men, Erection Hardness Score, and Difficulty in Performing Sexual Intercourse Questionnaire-5. Results: We enrolled 37 patients, and after 19 patients withdrew, 18 concluded the study without experiencing any adverse events. The mean patient age was 39.9 years. Geometric IELT after the 8-week training with the MTCK increased significantly (mean ± SE; 232.10 ± 72.16 seconds) vs baseline (103.91 ± 50.61 seconds, P = .006). Mean scores on the Premature Ejaculation Diagnostic Tool, Difficulty in Performing Sexual Intercourse Questionnaire-5, and Erection Hardness Score after 8-week training improved significantly vs the baseline values. The mean score on the Sexual Health Inventory for Men did not improve significantly after the 8-week training, but domain 1 did significantly improve after 8 weeks of MTCK use. Clinical Implications: The MTCK may be one possible treatment option for patients who are unable to delay ejaculation. Strengths and Limitations: This is the first study to show that the MTCK is effective for patients who are unable to delay ejaculation. A major limitation is that the present study was not strictly limited to an IELT <3 minutes. Conclusions: The MTCK may offer benefits not only for delay of ejaculation but also for erectile function.

Emerging Relationship between the Gut Microbiome and Prostate Cancer.

The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention. Prostate cancer cells are affected by direct contact with the microbiota of local tissues and urine, and a relationship between prostate cancer cells and the gut microbiota has been suggested. In the human gut microbiota, bacterial composition differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Moreover, the involvement of several intestinal bacteria in testosterone metabolism has been demonstrated, suggesting that they may affect prostate cancer progression and treatment through this mechanism. Basic research indicates that the gut microbiome also plays an important role in the underlying biology of prostate cancer through multiple mechanisms owing to the activity of microbial-derived metabolites and components. In this review, we describe the evidence surrounding the emerging relationship between the gut microbiome and prostate cancer, termed the "gut-prostate axis."

Low serum zinc concentration is associated with low serum testosterone but not erectile function.

OBJECTIVE: To investigate the relation between serum zinc concentration and several factors, including serum testosterone concentration and the score of questionnaires on sexual function in patients with sexual problems. METHODS: This study comprised 720 men (age, 46.3 [21-83] years) with some kind of sexual problem. Age, scores of the Sexual Health Inventory for Men and the Erection Hardness Score, and endocrinologic data including serum concentrations of testosterone, prostate-specific antigen, and zinc were included in this study. After serum zinc concentration of the men was classified into 5 groups (<70, 70≤ <80, 80≤ <90, 90≤ <100, ≤100 µg/dl), the relation of each parameter with serum zinc concentration was assessed for a trend analysis. Finally, the relation between serum concentrations of zinc and testosterone as well sexual function evaluated by the scores of the questionnaires was investigated. RESULTS: Only serum testosterone concentration (ptrend = 0.028) and serum cortisol concentration (ptrend = 0.003) showed a statistically significant relation to serum zinc concentration by trend analysis. Interestingly, trend analysis between serum concentrations of testosterone and zinc still showed a significant association after adjustment for serum cortisol concentration (ptrend = 0.032). However, no significant association was found in the relation between serum zinc concentration and the scores of the questionnaires after adjustment for serum concentrations of testosterone and cortisol. CONCLUSION: We clearly showed that after adjustment for serum cortisol concentration by trend analysis, serum testosterone concentration decreased as serum zinc concentration decreased, although sexual symptoms were not associated with this decrease.

International Prostate Symptom Score and Quality of Life Index for Lower Urinary Tract Symptoms Are Associated with Aging Males Symptoms Rating Scale for Late-Onset Hypogonadism Symptoms.

PURPOSE: Although patients with late-onset hypogonadism (LOH) often experience lower urinary tract symptoms (LUTS), LUTS are not generally included in LOH symptoms. No study has examined the direct relation of the Aging Males Symptoms rating scale (AMS) and the International Prostate Symptom Score (IPSS) with the quality of life (QOL) index. We analyzed the relation between the IPSS and QOL index and various factors including the AMS in patients with LOH syndromes. MATERIALS AND METHODS: This study comprised 1,688 men with LOH symptoms who visited our hospital or affiliated clinic. Factors associated with the IPSS were assessed in terms of age, scores of several questionnaires including the AMS, endocrinological variables, and serum concentration of PSA. Among these same factors, those associated with the QOL index were also evaluated. Finally, the same analyses were repeated in 187 patients with low serum testosterone concentration (<3.0 ng/mL). RESULTS: In a multivariate analysis using the significant items from the univariate analysis, AMS, age, and Erection Hardness Score correlated significantly with the IPSS. A trend analysis using items other than the AMS as adjustment factors also confirmed the relationship between an increase in QOL index and an increase in AMS. Similar results were obtained in the analysis of patients with low serum testosterone concentration. CONCLUSIONS: We revealed that the relation of IPSS with the QOL index for LUTS is closely associated with the AMS for LOH, regardless of testosterone level. When patients complain of LOH symptoms, a careful, detailed inquiry into LUTS is required.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Efficacy and patient satisfaction of low-intensity shockwave treatment for erectile dysfunction in a retrospective real-world study in Japan.

OBJECTIVES: To clarify the efficacy of low-intensity extracorporeal shockwave therapy for patients with erectile dysfunction, compare the efficacy between two types of lithotripters (ED1000 [focused type] and Renova [linear type]), and detect factors indicative of therapeutic gain with the treatment. METHODS: This retrospective study included 76 patients (52.8 ± 11.7 years) treated by ED1000 (12 times over 9 weeks) and 484 patients (52.5 ± 11.6 years) treated by Renova (4 times over 4 weeks). Age, sexual symptoms scores, and blood examinations were assessed. Efficacy was judged by improvement of the scores and patient satisfaction and compared between patients at 1 month after treatment with the lithotripters. Independent factors influencing efficacy by Renova were also assessed. RESULTS: Sexual symptom scores were improved significantly by both lithotripters, although the changes in the scores did not differ significantly between them. Efficacy rate as judged by patient satisfaction was 65.8% with the ED1000 and 71.1% with Renova, also without significant difference. Among several factors including age, sexual symptoms scores, endocrinological factors, metabolic factors, and the rate of phosphodiesterase type 5 inhibitor use, only age was found to be an independent factor influencing the efficacy of Renova. CONCLUSION: We clearly showed the high efficacy of both lithotripters. Although the efficacy rate did not differ between them, we speculated that the fewer treatment sessions needed with the Renova versus the ED1000 would be a great advantage for patients. We also suggest that Renova should be recommended for patients younger than 70 years of age.

Novel testosterone gel improves serum testosterone concentrations and aging males' symptoms in patients with late-onset hypogonadism: an active control equivalence, randomized, double-blind, crossover study.

Late-onset hypogonadism (LOH) is generally treated with testosterone replacement therapy. Intramuscular injection of testosterone enanthate is used for LOH in Japan but requires regular painful injections administered every 2-3 weeks at a clinic. Testosterone 2% (AndroForte 2® [AF2]) is available for treating LOH but is expensive because it is imported. We developed a new 2% testosterone gel (NTG) and hypothesized that in patients with LOH, NTG would improve serum testosterone concentrations and Aging Males' Symptoms (AMS) scores compared with AF2. We enrolled men with low levels of serum free testosterone (<11.8 pg/mL) and androgen deficiency symptoms (AMS score >27). The primary endpoint was equivalent change in serum testosterone concentrations with NTG compared to AF2. Secondary endpoints were equivalent change in AMS scores for each question with NTG compared to AF2. Each of AF2 or NTG was administered to the study subjects (23 men aged 42-71 years) for 4 weeks separated by a washout period of 2 weeks. The subjects were randomly divided into men who first received NTG and those who first received AF2. No subject experienced any adverse events throughout the study. Compared with the baseline values of serum testosterone, those following NTG and AF2 treatment were significantly higher and were also significantly higher in the subjects taking NTG versus AF2. NTG administration significantly improved the AMS score, whereas AF2 did not. This initial study has shown that this new NTG formulation may be effective in improving serum testosterone concentrations and also LOH-related symptoms.

Maximum Flow Rate is Lowest in the Early Morning in Hospitalized Men With Nocturia Evaluated Over 24 Hours by Toilet Uroflowmetry.

OBJECTIVES: To investigate urination parameters measured by toilet uroflowmetry in hospitalized men with nocturia over a 24-hour period to clarify the circadian rhythm of urination. Physicians often encounter male patients with complaints of low maximum flow rate only in the early morning. However, this has not been proved scientifically because most urinary examinations are generally performed for outpatients only during the daytime. METHODS: This retrospective study included 117 hospitalized male patients (age, 68.7 ± 12.8 years). The data of 4689 urinations during their hospital stay were evaluated on the ward by toilet uroflowmetry, which is a toilet-type device that allows patients to urinate as usual. The records including voided volume, maximum flow rate, and voiding time were evaluated as averages of 8 time periods of 3 hours each by generalized linear mixed models with an identity link function to adjust for personal bias. RESULTS: Voided volume after adjustment for age was significantly higher during the nighttime (21:00-06:00) than that in the morning (06:00-09:00) and highest from 00:00-03:00. Interestingly, even after adjustment for both voided volume and age, the maximum flow rate from 06:00-09:00 was the lowest. Voiding time after adjustment for age and voided volume was significantly higher during the nighttime (00:00-06:00) than that from 06:00-09:00. CONCLUSION: We clearly showed the circadian rhythm of urination in a group of hospitalized men with nocturia. Maximum flow rate was lowest in the early morning, including just after waking up.

Firmicutes in Gut Microbiota Correlate with Blood Testosterone Levels in Elderly Men.

PURPOSE: In males, testosterone levels have been implicated in various diseases. Recently, the influence of gut microbial-derived compounds on host metabolism has become evident, and it has been suggested that some gut bacteria may be involved in testosterone metabolism. In the present study, we examined the relationship between testosterone levels and gut microbiota in elderly Japanese men. MATERIALS AND METHODS: We collected samples from Japanese male subjects suspected of having prostate cancer and underwent prostate biopsies and excluded patients with positive biopsies to avoid the effect of prostate cancer on the gut microbiota. In total, 54 Japanese males with negative biopsy results were included in our study. The gut microbiota was analyzed by 16S rRNA gene sequencing of bacterial DNA extracted from rectal swabs. Gut microbiota compositions were compared between the two groups according to the level of serum testosterone (above or below 3.5 ng /mL). RESULTS: The median age of the cohort was 71 years, and the quartile range was 67 to 73 years. We observed no significant difference in alpha or beta diversity, but some bacteria belonging to the phylum Firmicutes (Clostridiales, Turicibacter, and Gemella) were increased in the high testosterone group. Serum testosterone levels positively correlated with the relative amount of Firmicutes (rS=0.3323, p=0.0141), and the amount of Firmicutes affected serum testosterone levels independent of host factors (age, body mass index, triglyceride, and total cholesterol; ß=0.770, p=0.0396). CONCLUSIONS: Some intestinal bacteria belonging to the phylum Firmicutes were associated with testosterone levels in elderly males. Therefore, the gut microbiota could affect testosterone metabolism in elderly males.

Efficacy and Safety of 5-Aminolevulinic Acid for Patients with Symptoms of Late-Onset Hypogonadism: A Preliminary Study.

PURPOSE: As the concept of late-onset hypogonadism (LOH) has gained increased attention, the treatment of eugonadal patients with LOH symptom has become a clinical problem. Previous studies have shown the possible benefits of 5-aminolevulinic acid (5-ALA) on the somatic, psychological and sexual functions. We therefore conducted this randomized, double-blind, placebo-controlled study to confirm the efficacy and safety of 5-ALA for LOH symptoms. MATERIALS AND METHODS: Thirty-two eugonadal subjects with LOH symptoms were randomly divided into a 5-ALA group (n=15) and a placebo group (n=17). Treatment was continued for 8 weeks. The change of the Aging Males' Symptoms (AMS) scale score and several biochemical and endocrinological variables during treatment were compared between the groups. RESULTS: After treatment, the change in the total AMS in the 5-ALA group was significantly greater than that in the placebo group (-7.4±4.7 vs. -4.9±4.9, p=0.029). However, the differences between the groups in the change of the somatic, psychological, and sexual sub-scores of the AMS did not reach the statistical significance, although these changes in the 5-ALA group were greater than those in the placebo group. Furthermore, the change in the biochemical and endocrinological variables in the two groups did not differ to a statistically significant extent. During the 8-week treatment period, no patients discontinued 5-ALA due to treatment-emergent adverse events (TEAEs). CONCLUSIONS: The intake of 5-ALA for 8 weeks was beneficial for eugonadal patients with symptoms of LOH and no severe TEAEs was experienced. 5-ALA should be considered as an option for those patients.

Pervasiveness of intronless genes expressed in haploid germ cell differentiation.

BACKGROUND: cDNA libraries derived from the brain and testis contain genes that encode almost all proteins. The brain is composed of various differentiated cells, and the testis also contains various differentiated cells, such as germ cells, and somatic cells that support germ cell differentiation, such as Sertoli and Leydig cells. Many genes appear to be expressed due to tissue complexity. METHODS: The Genome Project has sequenced the entire genomes of humans and mice. Recent research using new gene analysis technologies has found that many genes are expressed specifically in male germ cells. MAIN FINDINGS RESULTS: Functional intronless genes are significantly enriched in haploid germ cell-specific genes. CONCLUSION: Functional intronless genes associated with fertility are more likely to be inherited in haploid germ cells than in somatic cells.