Xinru Yu, Mingyue Jin, Yike Zhang, Yueran Lu, Runhe Zhu, Yi Fan Liu, Ying Jie Ma, Jingyan Song, Jinlong Sun
Oxidative stress (OS) significantly contributes to male reproductive dysfunction, a factor implicated in a substantial fraction of infertility cases. This comprehensive review elucidates the intricate interplay between oxidative stress and male reproductive health, emphasizing the molecular and cellular mechanisms through which reactive oxygen species (ROS) impair sperm function. Key areas of focus include lipid peroxidation of sperm membranes, DNA damage, and apoptotic cell death, which collectively undermine sperm viability and fertility potential. The discussion extends to the impact of lifestyle and environmental factors on oxidative balance, highlighting how these elements intensify oxidative stress and subsequently exacerbate reproductive outcomes. Advances in therapeutic approaches are critically assessed, particularly the development and application of antioxidants in ameliorating oxidative damage and restoring reproductive functions. This review also explores innovative diagnostic techniques for detecting ROS and assessing oxidative damage within clinical settings, offering insights into future directions for research and clinical practice in managing male infertility related to oxidative stress.
{"title":"Oxidative Stress and its Implications for Male Reproductive Dysfunction: Mechanistic Insights, Clinical Impacts, and Advances in Therapeutic Interventions.","authors":"Xinru Yu, Mingyue Jin, Yike Zhang, Yueran Lu, Runhe Zhu, Yi Fan Liu, Ying Jie Ma, Jingyan Song, Jinlong Sun","doi":"10.1111/andr.70143","DOIUrl":"https://doi.org/10.1111/andr.70143","url":null,"abstract":"<p><p>Oxidative stress (OS) significantly contributes to male reproductive dysfunction, a factor implicated in a substantial fraction of infertility cases. This comprehensive review elucidates the intricate interplay between oxidative stress and male reproductive health, emphasizing the molecular and cellular mechanisms through which reactive oxygen species (ROS) impair sperm function. Key areas of focus include lipid peroxidation of sperm membranes, DNA damage, and apoptotic cell death, which collectively undermine sperm viability and fertility potential. The discussion extends to the impact of lifestyle and environmental factors on oxidative balance, highlighting how these elements intensify oxidative stress and subsequently exacerbate reproductive outcomes. Advances in therapeutic approaches are critically assessed, particularly the development and application of antioxidants in ameliorating oxidative damage and restoring reproductive functions. This review also explores innovative diagnostic techniques for detecting ROS and assessing oxidative damage within clinical settings, offering insights into future directions for research and clinical practice in managing male infertility related to oxidative stress.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zihang Chen, Ming Wang, Qiushi Liu, Renliang Li, Xueping Zhang, Tommaso B Jannini, Emmanuele A Jannini, Xiansheng Zhang
Background: Premature ejaculation (PE) is one of the most prevalent sexual dysfunctions in males. Repetitive transcranial magnetic stimulation (TMS) demonstrates potential modulatory effects on ejaculatory function, however, the effects of different stimulation frequencies remain unclear.
Objectives: To investigate the effects of low-frequency and high-frequency rTMS in a rat model of rapid ejaculation and compare these outcome with dapoxetine, a standard pharmacological intervention.
Methods: Male rats exhibiting rapid ejaculation were identified based on sexual behavior parameters, then randomly allocated into four groups: 1-Hz rTMS, 10-Hz rTMS, dapoxetine control, and sham control groups. Ejaculatory behavior, hippocampal 5-hydroxytryptamine (5-HT) levels, brain-derived neurotrophic factor (BDNF) expression, and activation of the BDNF-receptor tyrosine kinase receptor B (TrkB) pathway were investigated before and after 2 weeks of treatment.
Results: Following 2 weeks of intervention, we found that all rTMS and dapoxetine groups showed significant improvements in ejaculation latency compared with controls, with the 10-Hz rTMS group showing the most substantial effect. While dapoxetine slightly outperformed 10-Hz rTMS in increasing 5-HT levels, 10-Hz rTMS induced a greater upregulation of BDNF and TrkB expression. Correlation analysis revealed that BDNF levels were positively associated with EL (r = 0.8817, p < 0.001) and negatively associated with ejaculation frequency (r = -0.8702, p < 0.001).
Conclusion: rTMS exhibited frequency-dependent therapeutic efficacy in rapid ejaculation rat models, with high-frequency protocols demonstrating superior benefits compared with low-frequency interventions. These effects are mediated through activation of the BDNF-TrkB pathway and enhanced serotonergic signaling, suggesting high-frequency rTMS as a promising non-pharmacological therapy for PE.
背景:早泄(PE)是男性最常见的性功能障碍之一。重复经颅磁刺激(TMS)显示了对射精功能的潜在调节作用,然而,不同刺激频率的影响尚不清楚。目的:研究低频和高频rTMS对大鼠快速射精模型的影响,并将这些结果与标准药物干预达泊西汀进行比较。方法:根据性行为参数识别出快速射精的雄性大鼠,随机分为4组:1 hz rTMS组、10 hz rTMS组、达泊西汀对照组和假对照组。研究了治疗前后两周的射精行为、海马5-羟色胺(5-HT)水平、脑源性神经营养因子(BDNF)表达和BDNF受体酪氨酸激酶受体B (TrkB)通路的激活情况。结果:干预2周后,我们发现所有rTMS组和达泊西汀组与对照组相比,射精潜伏期均有显著改善,其中10hz rTMS组效果最显著。虽然达泊西汀在增加5-HT水平方面略优于10-Hz rTMS,但10-Hz rTMS诱导BDNF和TrkB表达的上调幅度更大。相关分析显示,BDNF水平与EL呈正相关(r = 0.8817, p < 0.001),与射精频率呈负相关(r = -0.8702, p < 0.001)。结论:rTMS在快速射精大鼠模型中表现出频率依赖性的治疗效果,与低频干预相比,高频方案显示出更好的效果。这些作用是通过激活BDNF-TrkB通路和增强5 -羟色胺能信号传导介导的,表明高频rTMS是一种有希望的PE非药物治疗方法。
{"title":"Frequency-Dependent Effects of Repetitive Transcranial Magnetic Stimulation on Sexual Behavior Parameters in Premature Ejaculation Rodent Models.","authors":"Zihang Chen, Ming Wang, Qiushi Liu, Renliang Li, Xueping Zhang, Tommaso B Jannini, Emmanuele A Jannini, Xiansheng Zhang","doi":"10.1111/andr.70146","DOIUrl":"https://doi.org/10.1111/andr.70146","url":null,"abstract":"<p><strong>Background: </strong>Premature ejaculation (PE) is one of the most prevalent sexual dysfunctions in males. Repetitive transcranial magnetic stimulation (TMS) demonstrates potential modulatory effects on ejaculatory function, however, the effects of different stimulation frequencies remain unclear.</p><p><strong>Objectives: </strong>To investigate the effects of low-frequency and high-frequency rTMS in a rat model of rapid ejaculation and compare these outcome with dapoxetine, a standard pharmacological intervention.</p><p><strong>Methods: </strong>Male rats exhibiting rapid ejaculation were identified based on sexual behavior parameters, then randomly allocated into four groups: 1-Hz rTMS, 10-Hz rTMS, dapoxetine control, and sham control groups. Ejaculatory behavior, hippocampal 5-hydroxytryptamine (5-HT) levels, brain-derived neurotrophic factor (BDNF) expression, and activation of the BDNF-receptor tyrosine kinase receptor B (TrkB) pathway were investigated before and after 2 weeks of treatment.</p><p><strong>Results: </strong>Following 2 weeks of intervention, we found that all rTMS and dapoxetine groups showed significant improvements in ejaculation latency compared with controls, with the 10-Hz rTMS group showing the most substantial effect. While dapoxetine slightly outperformed 10-Hz rTMS in increasing 5-HT levels, 10-Hz rTMS induced a greater upregulation of BDNF and TrkB expression. Correlation analysis revealed that BDNF levels were positively associated with EL (r = 0.8817, p < 0.001) and negatively associated with ejaculation frequency (r = -0.8702, p < 0.001).</p><p><strong>Conclusion: </strong>rTMS exhibited frequency-dependent therapeutic efficacy in rapid ejaculation rat models, with high-frequency protocols demonstrating superior benefits compared with low-frequency interventions. These effects are mediated through activation of the BDNF-TrkB pathway and enhanced serotonergic signaling, suggesting high-frequency rTMS as a promising non-pharmacological therapy for PE.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: While metabolic disorders are well-established contributors to testosterone decline and erectile dysfunction (ED), little is known about the natural progression of reproductive parameters in healthy aging men.
Objectives: This study aimed to evaluate longitudinal changes in reproductive parameters and sought to determine the influence of body mass index (BMI) and glycated hemoglobin (HbA1c) on these changes.
Patients and methods: A total of 197 healthy men (aged 18-84 years) were assessed at baseline (FAMe 1), with 117 participants returning for follow-up (FAMe 2) after approximately 6 years. All participants underwent a thorough andrological examination.
Results: Total and free testosterone levels declined significantly over 6 years in men older than 25 years at baseline (p < 0.05). FSH levels increased significantly in men older than 35 years at FAMe 1 (p < 0.05), while LH and SHBG remained unchanged. Despite moderate declines, semen parameters remained mostly within physiological limits. Erectile function exhibited a moderate but progressive decline (p < 0.001). In men over 45 years, neither age (p = 0.13) nor testosterone (p = 0.52) influenced erectile function, while an increment of HbA1c levels was significantly associated with deteriorating erectile function (p = 0.002). Similarly, AMS scores significantly increased after age 45, which was strongly correlated with higher HbA1c levels (p = 0.001).
Discussion: While testosterone levels declined with aging, they remained within the normal range, suggesting that healthy men experience only apparently mild reproductive aging. Erectile function and hypogonadism-like symptoms were more strongly associated with glycemic control than with testosterone levels.
Conclusion: In healthy men, reproductive and sexual aging occur gradually, with testosterone and semen parameters largely preserved over time. However, metabolic health, rather than testosterone, plays a key role in the progression of ED and hypogonadism-like symptoms, emphasizing the need for preventive metabolic interventions to maintain reproductive health.
{"title":"Healthy Aging Men Do Not Suffer From Relevant Limitations of Their Reproductive Functions.","authors":"Simone Bier, Jann-Frederik Cremers, Phillip Schrage, Amelie Körtje, Claudia Krallmann, Sabine Kliesch, Jörg Gromoll, Sandra Laurentino, Michael Zitzmann","doi":"10.1111/andr.70147","DOIUrl":"https://doi.org/10.1111/andr.70147","url":null,"abstract":"<p><strong>Background: </strong>While metabolic disorders are well-established contributors to testosterone decline and erectile dysfunction (ED), little is known about the natural progression of reproductive parameters in healthy aging men.</p><p><strong>Objectives: </strong>This study aimed to evaluate longitudinal changes in reproductive parameters and sought to determine the influence of body mass index (BMI) and glycated hemoglobin (HbA1c) on these changes.</p><p><strong>Patients and methods: </strong>A total of 197 healthy men (aged 18-84 years) were assessed at baseline (FAMe 1), with 117 participants returning for follow-up (FAMe 2) after approximately 6 years. All participants underwent a thorough andrological examination.</p><p><strong>Results: </strong>Total and free testosterone levels declined significantly over 6 years in men older than 25 years at baseline (p < 0.05). FSH levels increased significantly in men older than 35 years at FAMe 1 (p < 0.05), while LH and SHBG remained unchanged. Despite moderate declines, semen parameters remained mostly within physiological limits. Erectile function exhibited a moderate but progressive decline (p < 0.001). In men over 45 years, neither age (p = 0.13) nor testosterone (p = 0.52) influenced erectile function, while an increment of HbA1c levels was significantly associated with deteriorating erectile function (p = 0.002). Similarly, AMS scores significantly increased after age 45, which was strongly correlated with higher HbA1c levels (p = 0.001).</p><p><strong>Discussion: </strong>While testosterone levels declined with aging, they remained within the normal range, suggesting that healthy men experience only apparently mild reproductive aging. Erectile function and hypogonadism-like symptoms were more strongly associated with glycemic control than with testosterone levels.</p><p><strong>Conclusion: </strong>In healthy men, reproductive and sexual aging occur gradually, with testosterone and semen parameters largely preserved over time. However, metabolic health, rather than testosterone, plays a key role in the progression of ED and hypogonadism-like symptoms, emphasizing the need for preventive metabolic interventions to maintain reproductive health.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suleman Arshad, Taha Yahya, Syed Ali Raza Zaidi, Meer Hassan Khalid
{"title":"Letter to Editor: Sexual Dysfunctions in Inflammatory Bowel Disease: Role of Mediterranean Diet and Quality of Life.","authors":"Suleman Arshad, Taha Yahya, Syed Ali Raza Zaidi, Meer Hassan Khalid","doi":"10.1111/andr.70148","DOIUrl":"https://doi.org/10.1111/andr.70148","url":null,"abstract":"","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Margarida Henriques, Simone Cilio, Pedro Ramos, Georgios Tsampoukas, Marco Capece, Luca Boeri, Edoardo Pozzi, Savio Domenico Pandolfo, Paolo Verze, Andrea Salonia, Carlos Martins-Silva, Afonso Morgado
Background: Male sexual dysfunctions (SDs) like erectile dysfunction (ED), premature ejaculation (PE), and Peyronie's disease (PD) are highly prevalent conditions affecting the quality of life of men and their partners. Botulinum toxin (BTX) is emerging as a promising injectable therapy to treat male SDs.
Objective: To systematically review the current evidence on the use of BTX in the treatment of male SDs.
Materials and methods: PubMed, Cochrane, and EMBASE databases were queried for all published studies indexed up to October 2024 using predefined keywords.
Results: Of 108 identified articles, 9 (6 on ED, 2 on PE, and only 1 on PD) met our inclusion criteria. In ED, BTX improved International Index of Erectile Function-Erectile Function domain (IIEF-EF) scores in 41%-57.4% of patients, with benefits lasting up to 6 months. In PE, BTX increased ejaculation latency and subjective satisfaction at 1-3 months, but the effects diminished by 6 months. In PD, a single study showed a significant reduction in penile curvature (-7.9°), plaque thickness, and penile pain. Adverse effects were mild and local, reported in less than 10% of cases.
Conclusions: BTX injections demonstrate promising improvements in erectile function, ejaculation latency, and penile curvature with a favourable safety profile. However, current evidence is limited by small, heterogeneous studies and the absence of large randomized controlled trials. Further research is needed to establish optimal dosing, timing, and patient selection.
{"title":"A Systematic Review on Administration of Botulinum Toxin in the Management of Male Sexual Dysfunctions.","authors":"Margarida Henriques, Simone Cilio, Pedro Ramos, Georgios Tsampoukas, Marco Capece, Luca Boeri, Edoardo Pozzi, Savio Domenico Pandolfo, Paolo Verze, Andrea Salonia, Carlos Martins-Silva, Afonso Morgado","doi":"10.1111/andr.70142","DOIUrl":"https://doi.org/10.1111/andr.70142","url":null,"abstract":"<p><strong>Background: </strong>Male sexual dysfunctions (SDs) like erectile dysfunction (ED), premature ejaculation (PE), and Peyronie's disease (PD) are highly prevalent conditions affecting the quality of life of men and their partners. Botulinum toxin (BTX) is emerging as a promising injectable therapy to treat male SDs.</p><p><strong>Objective: </strong>To systematically review the current evidence on the use of BTX in the treatment of male SDs.</p><p><strong>Materials and methods: </strong>PubMed, Cochrane, and EMBASE databases were queried for all published studies indexed up to October 2024 using predefined keywords.</p><p><strong>Results: </strong>Of 108 identified articles, 9 (6 on ED, 2 on PE, and only 1 on PD) met our inclusion criteria. In ED, BTX improved International Index of Erectile Function-Erectile Function domain (IIEF-EF) scores in 41%-57.4% of patients, with benefits lasting up to 6 months. In PE, BTX increased ejaculation latency and subjective satisfaction at 1-3 months, but the effects diminished by 6 months. In PD, a single study showed a significant reduction in penile curvature (-7.9°), plaque thickness, and penile pain. Adverse effects were mild and local, reported in less than 10% of cases.</p><p><strong>Conclusions: </strong>BTX injections demonstrate promising improvements in erectile function, ejaculation latency, and penile curvature with a favourable safety profile. However, current evidence is limited by small, heterogeneous studies and the absence of large randomized controlled trials. Further research is needed to establish optimal dosing, timing, and patient selection.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}