PURPOSE:Antioxidant (AOX) therapy has long been investigated for the management of male infertility. It has potential benefits, but persistent controversy affects its broad acceptance and clinical utility. This study aimed to develop standardized, evidence-based guidelines for AOX use by synthesizing the best available evidence and achieving global expert consensus. MATERIALS AND METHODS:A comprehensive literature review was conducted by senior experts of the Global Andrology Forum (GAF). Additionally, data on the real-life use of oxidative stress (OS) testing and AOX use obtained from the largest global survey of practicing physicians conducted by GAF, which served as a reference point for this study. In phase one, 151 international specialists (>5 years' experience) participated in a modified Delphi process to evaluate AOX therapy in male infertility. Experts reviewed draft statements and rated agreement on a 10-point Likert scale. Statements achieving >80% consensus (with score >7/10) were accepted. The original eight statements were expanded to 19 and finalized into 18. In phase two, 84 senior physicians (>10 years' experience) graded the Delphi-approved statements using the GRADE approach. RESULTS:Four out of the 18 statements failed to reach consensus and were excluded. Of the final 14 statements, seven (50%) were graded as "Strong" and seven (50%) as "Weak." Current evidence indicates that AOX therapy can reduce OS, improve sperm quality, and potentially enhance reproductive outcomes. However, benefits vary by agent, regimen, and patient population. The guidelines emphasize the need to document OS and to consider underlying factors before initiating AOX therapy, and caution against indiscriminate or prolonged use. CONCLUSIONS:Developed through a dual-validation process and endorsed by a globally diverse expert panel, these GAF guidelines represent the first standardized, evidence-based guidelines for AOX use in male infertility. By addressing heterogeneity in research and practice, they provide clinicians with practical, safe, and patient-centered recommendations for rational AOX therapy worldwide.

PURPOSE:Phosphodiesterase type 5 inhibitors (PDE5i) are widely used to treat erectile dysfunction (ED). However, a subset of men does not respond to these agents or seek restoration of natural erections. Regenerative therapies (RT), including low-intensity shock wave therapy (LiSWT), platelet-rich plasma (PRP) therapy, and stem cell therapy (SCT), have emerged as potential alternative treatment options. This article reviews the available evidence and presents the Global Andrology Forum (GAF) graded statements and recommendations for the use of RT in ED. MATERIALS AND METHODS:A GAF expert panel conducted a literature review of the PubMed and Scopus databases up to February 2025 to identify studies on RT for ED. Surveys and a modified Delphi consensus method were employed to develop position statements and clinical recommendations. These were graded according to the "GRADE" classification system as either "strong" or "weak." Recommendations receiving strong ratings from at least 80% of experts were classified as "strong," while others were classified as "weak." RESULTS:Seventeen statements and recommendations were accepted and graded by a panel of 36 GAF experts from 18 countries. Eleven were classified as "strong," and six as "weak." CONCLUSIONS:Current evidence indicates modest short-term benefits of LiSWT in young and middle-aged men with mild-to-moderate vasculogenic ED. The efficacy of PRP and SCT remains uncertain. The GAF statements and recommendations highlight the lack of standardized treatment protocols and insufficient evidence of long-term effectiveness and emphasize the need for further research and clinical trials. Meanwhile, patients and healthcare providers should remain cautious when applying RT for ED. Clinicians should avoid overclaiming the benefits of RT to patients and provide a realistic prognosis based on current evidence.

OBJECTIVE:This study aimed to examine trends in frequency of sexual intercourse and sexual function among Japanese men over the past 30 years by comparing the Nationwide Survey conducted by the Japanese Society for Sexual Medicine in 2023 with the Sapporo Survey conducted by the Department of Urology, Sapporo Medical University, in 1991. METHODS:Three domains were analyzed: sexual intercourse, penile rigidity, and morning erections in both studies. To minimize inconsistencies, definitions were standardized. The 2023 survey included 3795 men aged 20-79 years, while the 1991 survey comprised 8893 participants for sexual intercourse, 7517 for morning erections, and 3886 for penile rigidity. Case numbers differed by item in 1991 owing to incomplete responses. The 1991 survey targeted only married individuals; comparable analyses were performed using married participants extracted from the 2023 dataset. RESULTS:1. Sexual intercourse: Compared with the 1991 Sapporo Survey, the proportion of men reporting sexual intercourse less than once per month was significantly higher across all age groups in the 2023 Nationwide Survey, except among men in their 20s. 2. Penile rigidity: The proportion of men with insufficient penile rigidity for penetration was significantly higher in 2023 than in 1991 across all age groups except those aged ≥ 75 years. 3. Morning erections: Men reporting complete absence of morning erections were significantly more common in 2023 across all age groups. CONCLUSION:Over the past three decades, Japanese men have shown substantial declines in the frequency of sexual intercourse, penile rigidity, and the frequency of morning erections, particularly in younger and middle-aged cohorts.

OBJECTIVES:To investigate the efficacy of desmopressin in older men with persistent nocturia due to nocturnal polyuria and then determine the independent factors affecting the efficacy of desmopressin. METHODS:Desmopressin 50 mg was administered for 12 weeks to 49 patients (76.3 ± 7.3 years) with persistent nocturia. Physical factors including prostate volume, muscle mass, basal metabolic rate, maximum flow rate, voiding diary, serum sodium, and scores of several questionnaires were evaluated. First, we evaluated the efficacy of desmopressin and then investigated the independent factors influencing its efficacy. RESULTS:Nocturnal urinary frequency decreased significantly from 3.9 ± 1.0 to 1.9 ± 1.1 times/night. The nocturnal urine volume and nocturnal polyuria index significantly decreased from 761.6 ± 273.8 to 445.5 ± 159.3 mL and from 45.5% ± 10.2% to 32.3% ± 14.4% respectively. The total International Prostate Symptom Score improved significantly, as did the Quality of Life index. However, the Overactive Bladder Symptom Score and the Athens Insomnia Scale did not show significant improvement. Only muscle mass at the baseline measurement was identified as a factor predictive of affecting the efficacy of desmopressin based on the decrease in nocturnal urinary frequency. CONCLUSIONS:This study is the first, to our knowledge, to determine the independent factors affecting the efficacy of desmopressin.

Purpose:We aimed to evaluate the sexual function in newlywed men or men just before marriage to better understand the current situation of the male sexual and reproductive function. Methods:This study included 719 men visiting our hospital or clinic for fertility screening. Patient characteristics including age, sexual status, semen parameters, several symptoms, and blood analysis results were assessed. We compared several factors between patients with sexual dysfunction (SD group) and those with normal sexual function (SN group), and performed univariate and multivariate analyses to identify independent risk factors for sexual dysfunction. Results:Of 719 men, 139 (19.3%) were identified as having sexual dysfunction, including erectile dysfunction [ED], n = 88 [12.2%]; ejaculatory dysfunction, n = 66 [9.1%]; and decreased libido, n = 35 [4.9%]. Significant differences between the SD and SN groups were observed in age, albumin, liver enzymes, triglycerides, blood sugar, and semen volume. In a multivariate analysis, only age, body mass index, and the Beck Depression Inventory score for depression remained significant risk factors for sexual dysfunction. Conclusions:It was considered that men who are older, obese, or exhibit depressive symptoms are likely to experience sexual dysfunction before the initiation of fertility treatment.

PURPOSE:Depressive symptoms related to late-onset hypogonadism (LOH) have attracted attention due to their impact on absenteeism and presenteeism. Although LOH symptoms are not consistently associated with serum testosterone levels, elevated cortisol and decreased dehydroepiandrosterone sulfate (DHEA-S) are frequently observed in depressed individuals, suggesting their potential as biomarkers. We investigated the relationship between depressive symptoms and the DHEA-S/cortisol (D/C) ratio in a large cohort of males with LOH symptoms. MATERIALS AND METHODS:We retrospectively analyzed data from 3,005 males with LOH symptoms who visited our hospital or affiliates between May 2016 and March 2024. Symptoms were assessed using the Aging Male Symptoms (AMS) scale, Sexual Health Inventory for Men, International Prostate Symptom Score, and Beck Depression Inventory (BDI). Endpoints included correlations between serum testosterone and D/C ratio, associations between the D/C ratio and AMS and BDI scores, and multivariable-adjusted relationships between the D/C ratio and symptom scores. RESULTS:The mean age was 47.5±12.3 years, mean serum testosterone of 5.4±2.4 ng/mL and mean D/C ratio of 33.8±29.2. No significant correlation was observed between testosterone and D/C ratio (p=0.368). In contrast, the D/C ratio showed significant negative correlations with AMS (r=-0.058, p=0.001) and BDI (r=-0.085, p<0.001) scores. Trend analysis demonstrated a decline in the D/C ratio with increasing AMS and BDI severity (p for trend<0.001). Testosterone showed no association with AMS or BDI scores. After adjusting for age, aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, triglyceride, hemoglobin A1c, only the BDI score remained associated with the D/C ratio (β=-0.054, p=0.002). CONCLUSIONS:The D/C ratio demonstrates a significant association with depressive symptoms and may serve as a potential biomarker. Its assessment may improve psychological evaluations and management in this population.

PURPOSE:Non-obstructive azoospermia (NOA), defined as the absence of sperm in the ejaculate due to testicular failure, is observed in 5% to 15% of infertile men and accounts for two-thirds of azoospermia cases. The management of NOA is marked by significant controversy and global variation in diagnostic and therapeutic approaches, highlighting the crucial need for well-designed and standardized clinical practice guidelines. We present comprehensive graded clinical practice recommendations and statements for diagnosing and treating NOA, aiming to establish standardized strategies that can globally help guide practitioners in their practice. MATERIALS AND METHODS:A comprehensive literature review was conducted to gather evidence on the epidemiological, diagnostic, and therapeutic aspects of NOA. The Global Andrology Forum (GAF) recommendations were developed through the collaboration of a global panel of experts using the Delphi method and surveys to achieve consensus. Statements were graded according to the Oxford Centre for Evidence-Based Medicine "GRADE" classification as either "Strong" or "Weak." Statements receiving at least 80% expert consensus were graded as "Strong," while others were categorized as "Weak." RESULTS:The GAF has formulated a total of 49 recommendations and statements on the diagnosis and treatment of NOA, including 21 for diagnosis and 28 for treatment. The recommendations and statements were evaluated and graded by a panel of 48 GAF experts from 25 countries worldwide. The majority of experts (60.5%) had more than 10 years of clinical experience in managing NOA. CONCLUSIONS:The GAF guidelines address discrepancies in NOA management across diverse clinical settings and provide comprehensive graded recommendations to guide clinicians in its diagnosis and treatment. Developed and graded by a large worldwide panel of experts, the current guidelines present simplified, high-standard strategies that can be seamlessly integrated into the daily global practice, offering practitioners a clear framework for managing NOA.

PURPOSE:To evaluate the evidence on sperm DNA fragmentation (SDF) and its clinical applications in reproductive medicine, highlighting benefits, limitations, and guidelines for its use to assist clinicians in objective decision-making. MATERIALS AND METHODS:A multidisciplinary team of clinicians and reproductive experts from the Global Andrology Forum (GAF) reviewed the latest evidence on SDF, covering indications, testing methods, recurrent pregnancy loss, varicocele and its repair, assisted reproductive technologies (ART), treatment of associated conditions, antioxidant therapy, and sperm selection for ART. Expert statements and recommendations were developed and graded with the GRADE system using a modified Delphi process. RESULTS:Based on the GAF surveys, systematic reviews, and meta-analyses related to SDF, 52 experts introduced and scored 24 statements and recommendations using the GRADE system. Of these, 87.5% (21/24) achieved strong ratings, reflecting broad consensus, while 12.5% (3/24) were rated weak. The guidelines provide evidence-based recommendations for clinical scenarios, including the role of SDF in infertility, recurrent pregnancy loss, and ART outcomes. CONCLUSIONS:While there is growing interest and evidence regarding the clinical benefit of SDF testing and its utility in managing male infertility, significant gaps in the literature limit its routine use in clinical practice. The guidelines offer a structured framework for integrating SDF testing into male infertility management, emphasizing a tailored approach based on individual clinical scenarios. Clinicians must balance the benefits and limitations of SDF testing and antioxidant treatment to optimize care in reproductive medicine. These guidelines are critical for advancing evidence-based practices in male infertility management.

OBJECTIVE:To clarify the efficacy and safety of testosterone replacement treatment for eugonadal patients with symptoms of late-onset hypogonadism. MATERIALS AND METHODS:565 eugonadal men with symptoms of late-onset hypogonadism who underwent testosterone replacement treatment were included in this study. Physical factors, laboratory and endocrinologic variables, and scores of several questionnaires were evaluated. Testosterone replacement treatment was administered with intramuscular injection of 250 mg of testosterone esters, and efficacy was assessed by patient satisfaction. First, we evaluated the efficacy rate and safety of testosterone replacement treatment and then investigated the independent factors influencing its efficacy. RESULTS:Testosterone replacement treatment was effective in 131 of 216 patients (60.6%), 111 of 163 patients (68.1%), and 126 of 186 patients (67.7%) with mental, physical, and sexual dysfunction, respectively. The overall efficacy rate was 65.1%. No side effects were observed after testosterone replacement treatment. Only the total score of the Aging Male Symptoms rating scale was identified as a factor predictive of patient satisfaction. CONCLUSIONS:This study is the first, to our knowledge, to report the efficacy and safety of testosterone replacement treatment for eugonadal men with symptoms of late-onset hypogonadism.

Purpose: The prevalence of liver dysfunction among men has been steadily increasing in recent decades. Among the various non-invasive assessment tools available, the Fibrosis-4 (FIB-4) Index has emerged as a particularly valuable and widely adopted scoring system for evaluating liver fibrosis. This study investigated the relationship between liver fibrosis evaluated by the FIB-4 Index and male health care parameters. Materials and Methods: Participants were assessed using standardized questionnaires, including the International Prostate Symptom Score (IPSS) for lower urinary tract symptoms (LUTS), the Sexual Health Inventory for Men (SHIM) and EHS (Erection Hardness Score) for erectile function, and the AMS (Aging Males Symptoms rating scale) for late onset hypogonadism. Endocrinological parameters, including dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor 1 (IGF-1), total testosterone and cortisol levels, as well as metabolic factors, including hemoglobin A1c (HbA1c) and triglyceride level, were evaluated as potential confounders. Results: The patient age was 50.62±0.24 years. The analysis revealed significant associations between higher FIB-4 Index quintiles and worsening sexual function and LUTS. Among endocrine factors, DHEA-S and IGF-1 exhibited decreasing trends with higher FIB-4 Index values, whereas cortisol showed an increasing trend. Surprisingly, no significant association was observed between FIB-4 Index and testosterone levels. HbA1c increased, but triglycerides did not correlate with FIB-4. Multiple regression confirmed IPSS and SHIM scores were independently linked to the FIB-4 Index (p<0.05). Conclusions: These findings highlight the importance of hepatic assessment in men with erectile dysfunction and LUTS, supporting a multidisciplinary approach to care.

To evaluate the current perspectives on reporting success rates for assisted reproductive technology, the authors conducted a nationwide survey. Of the 327 facilities that responded (response rate: 53.5%), over half recognized potential benefits of reporting in vitro fertilization (IVF) success rates, such as aiding patients in selecting a clinic (68.5%) and enhancing the quality and efficiency of information provided to patients (62.1%). However, concerns regarding potential negative impacts, including patient selection bias, were also highlighted, albeit to a lesser extent (32.7%–52.3%). These findings underscore the need for further discussions to establish an unbiased reporting framework and improve patient education on assisted reproductive technology (ART) success rates.

PURPOSE:Premature ejaculation (PE) is a most common sexual complaint among men worldwide, but its prevalence and associated factors in Japan remain underexplored. This study aimed to determine the prevalence of self-reported PE, lifelong PE (LPE), and acquired PE (APE) among Japanese men, as well as to identify associated factors, distress levels, and healthcare-seeking behaviors through a nationwide cross-sectional survey. MATERIALS AND METHODS:This internet-based nationwide cross-sectional survey was conducted among Japanese men from 20 to 79 years old by the Clinical Research Promotion Committee of the Japanese Society for Sexual Medicine (JSSM). Data were collected using validated questionnaires, including the International Society for Sexual Medicine (ISSM) criteria for LPE and APE. RESULTS:Of 37,485 invited participants, 6,228 provided valid responses (response rate: 16.61%), with 5,331 sexually active men included in the analysis. The prevalence of self-reported PE distress was 23.39%. ISSM-defined LPE and APE were observed in 0.54% and 3.47% of respondents, respectively. Univariate analysis identified erectile dysfunction (ED), psychotropic drug use, neurological diseases, trauma, aortic aneurysm surgery, and partnership dissatisfaction as significant associated factors for both LPE and APE. Multivariate analysis confirmed ED as the common associated factor. Despite 51.00% of respondents expressing a desire for treatment, only 4.81% had sought medical help. CONCLUSIONS:This study provides the first epidemiological insights into PE in Japan, revealing a notable prevalence and identifying ED as a key associated factor. Despite significant distress, most affected individuals do not seek medical help, highlighting the necessity for greater public awareness and better access to treatment options. Future research should focus on longitudinal assessments to explore causal relationships and evaluate potential interventions.

These 2024 guidelines address male infertility amid Japan's declining birth rate, following the recent provision of national health insurance coverage for infertility treatments. Male factors contribute to approximately 50% of infertility cases, with spermatogenic dysfunction being the most common cause (82.4%). The guidelines provide evidence-based recommendations for diagnosing and treating male infertility. Diagnostic approaches include comprehensive medical history, physical examination, semen analysis, hormone testing, genetic testing for severe cases, and appropriate imaging studies. Treatment recommendations cover both medical and surgical interventions. Medical treatments include gonadotropin therapy for hypogonadotropic hypogonadism (grade A), clomiphene citrate for oligozoospermia with low testosterone (grade B), and antioxidant therapy (limited evidence: grade C). Surgical treatments focus on varicocelectomy for palpable varicoceles (grade A), with microsurgical approaches preferred. Nonobstructive azoospermia is treated by microdissection testicular sperm extraction (micro-TESE) (grade A). The guidelines also emphasize preserving fertility before cancer treatment, managing sexual dysfunction with PDE5 inhibitors (grade A), and treating retrograde ejaculation with tricyclic antidepressants (grade B).