Pub Date : 2025-05-09DOI: 10.1038/s41585-025-01032-8
Bryan D. Naelitz, Leila Momtazi-Mar, Sanjay Vallabhaneni, Rossella Cannarella, Sarah C. Vij, Neel V. Parekh, Raevti Bole, Scott D. Lundy
Testosterone has a pivotal role in spermatogenesis, erectile function, libido and expression of secondary sexual characteristics. The prevalence of symptomatic, laboratory-proven testosterone deficiency increases with age and is often treated with testosterone replacement therapy (TRT). Treatment with exogenous androgens suppresses gonadotropin levels, inhibits endogenous testosterone production and drastically reduces intratesticular testosterone, consequently impairing spermatogenesis. Sperm production often slowly resumes after TRT cessation. However, the rate of recovery shows highly variable kinetics that might complicate family planning. Medical therapies (including aromatase inhibitors and selective oestrogen receptor antagonists) and exogenous gonadotropins (including human chorionic gonadotropin and follicle-stimulating hormone) may be used to preserve or restore spermatogenesis in select populations receiving TRT. Exogenous testosterone is contraindicated in men trying to conceive, but new short-acting formulations, including oral testosterone undecanoate and nasal testosterone gel, might incompletely suppress the hypothalamic–pituitary–gonadal axis and partially preserve spermatogenesis. Testosterone replacement therapy is commonly used to treat symptomatic, laboratory-proven testosterone deficiency, but can have detrimental effects on spermatogenesis, which is troublesome in men of reproductive age. This Review describes therapeutic options for testosterone deficiency in the reproductive-aged males, discussing medical therapies with the potential to preserve or restore spermatogenesis in selected patients receiving testosterone replacement therapy.
{"title":"Testosterone replacement therapy and spermatogenesis in reproductive age men","authors":"Bryan D. Naelitz, Leila Momtazi-Mar, Sanjay Vallabhaneni, Rossella Cannarella, Sarah C. Vij, Neel V. Parekh, Raevti Bole, Scott D. Lundy","doi":"10.1038/s41585-025-01032-8","DOIUrl":"10.1038/s41585-025-01032-8","url":null,"abstract":"Testosterone has a pivotal role in spermatogenesis, erectile function, libido and expression of secondary sexual characteristics. The prevalence of symptomatic, laboratory-proven testosterone deficiency increases with age and is often treated with testosterone replacement therapy (TRT). Treatment with exogenous androgens suppresses gonadotropin levels, inhibits endogenous testosterone production and drastically reduces intratesticular testosterone, consequently impairing spermatogenesis. Sperm production often slowly resumes after TRT cessation. However, the rate of recovery shows highly variable kinetics that might complicate family planning. Medical therapies (including aromatase inhibitors and selective oestrogen receptor antagonists) and exogenous gonadotropins (including human chorionic gonadotropin and follicle-stimulating hormone) may be used to preserve or restore spermatogenesis in select populations receiving TRT. Exogenous testosterone is contraindicated in men trying to conceive, but new short-acting formulations, including oral testosterone undecanoate and nasal testosterone gel, might incompletely suppress the hypothalamic–pituitary–gonadal axis and partially preserve spermatogenesis. Testosterone replacement therapy is commonly used to treat symptomatic, laboratory-proven testosterone deficiency, but can have detrimental effects on spermatogenesis, which is troublesome in men of reproductive age. This Review describes therapeutic options for testosterone deficiency in the reproductive-aged males, discussing medical therapies with the potential to preserve or restore spermatogenesis in selected patients receiving testosterone replacement therapy.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 10","pages":"703-719"},"PeriodicalIF":14.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-30DOI: 10.1038/s41585-025-01030-w
Alisa J. Stephens Shields, J. Quentin Clemens, Michel A. Pontari, H. Henry Lai, Robert Moldwin, David A. Williams, Catherine S. Bradley, John T. Farrar, J. Richard Landis, Chris Mullins, Bruce D. Naliboff, Siobhan Sutcliffe, Stephen J. Walker, Claire C. Yang, Daniel J. Clauw
Randomized clinical trials have resulted in few approved therapies for the treatment of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urologic chronic pelvic pain syndrome. Heterogenous patient populations, mismatches of treatments to patient phenotypes, non-specific outcomes and use of standard study designs not leveraging phenotypic heterogeneity might have contributed to the inability of previous trials to demonstrate existing efficacy. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network has identified important phenotypic characteristics associated with differential symptom severity and treatment responsiveness. Based on Multidisciplinary Approach to the Study of Chronic Pelvic Pain findings and external research, empirically informed strategies were generated for defining patient populations, specifying treatments and selecting primary outcomes for future randomized clinical trials in urologic chronic pelvic pain syndrome. Explicitly specifying the scope of eligibility criteria across heterogeneous patient subgroups defined by pain widespreadness, the presence of Hunner lesions, the presence of pain with bladder filling or relieved by voiding, the extent of chronic overlapping pain conditions, and pelvic floor tenderness is needed. Therapies should be selected based on the mechanism of action and relevance to the mechanism of pain and dominant symptomology that the patient experiences. Evidence suggests that pain and urinary symptoms should be evaluated separately. Promising trial designs for identifying effective therapies in this heterogeneous patient population include sequential multiple assignment randomized trials and adaptive designs. This Expert Recommendation from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network provides informed considerations and a greatly expanded foundation that can be used to refine the design of future therapeutic clinical trials in urologic chronic pelvic pain syndrome.
{"title":"Towards precision medicine in clinical trials for the treatment of urologic chronic pelvic pain syndrome: lessons from the MAPP Research Network","authors":"Alisa J. Stephens Shields, J. Quentin Clemens, Michel A. Pontari, H. Henry Lai, Robert Moldwin, David A. Williams, Catherine S. Bradley, John T. Farrar, J. Richard Landis, Chris Mullins, Bruce D. Naliboff, Siobhan Sutcliffe, Stephen J. Walker, Claire C. Yang, Daniel J. Clauw","doi":"10.1038/s41585-025-01030-w","DOIUrl":"10.1038/s41585-025-01030-w","url":null,"abstract":"Randomized clinical trials have resulted in few approved therapies for the treatment of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urologic chronic pelvic pain syndrome. Heterogenous patient populations, mismatches of treatments to patient phenotypes, non-specific outcomes and use of standard study designs not leveraging phenotypic heterogeneity might have contributed to the inability of previous trials to demonstrate existing efficacy. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network has identified important phenotypic characteristics associated with differential symptom severity and treatment responsiveness. Based on Multidisciplinary Approach to the Study of Chronic Pelvic Pain findings and external research, empirically informed strategies were generated for defining patient populations, specifying treatments and selecting primary outcomes for future randomized clinical trials in urologic chronic pelvic pain syndrome. Explicitly specifying the scope of eligibility criteria across heterogeneous patient subgroups defined by pain widespreadness, the presence of Hunner lesions, the presence of pain with bladder filling or relieved by voiding, the extent of chronic overlapping pain conditions, and pelvic floor tenderness is needed. Therapies should be selected based on the mechanism of action and relevance to the mechanism of pain and dominant symptomology that the patient experiences. Evidence suggests that pain and urinary symptoms should be evaluated separately. Promising trial designs for identifying effective therapies in this heterogeneous patient population include sequential multiple assignment randomized trials and adaptive designs. This Expert Recommendation from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network provides informed considerations and a greatly expanded foundation that can be used to refine the design of future therapeutic clinical trials in urologic chronic pelvic pain syndrome.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 9","pages":"632-642"},"PeriodicalIF":14.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-29DOI: 10.1038/s41585-025-01038-2
Maetal E. Haas Kogan, Barbara Chubak, Elizabeth R. Boskey, Steven J. Staffa, Carl G. Streed Jr, Katharine B. Dalke, Arlene Baratz, Cecile Ferrando, Frances W. Grimstad
The surgical care of patients with differences in sex development (DSD) or intersex traits has historically been the domain of paediatric subspecialties. However, as patients defer surgeries until later in life, providers are needed to help close this emerging clinical care gap for the LGBTQIA+ community.
{"title":"Reconstructive urologists can address the care gap for adults with intersex traits","authors":"Maetal E. Haas Kogan, Barbara Chubak, Elizabeth R. Boskey, Steven J. Staffa, Carl G. Streed Jr, Katharine B. Dalke, Arlene Baratz, Cecile Ferrando, Frances W. Grimstad","doi":"10.1038/s41585-025-01038-2","DOIUrl":"10.1038/s41585-025-01038-2","url":null,"abstract":"The surgical care of patients with differences in sex development (DSD) or intersex traits has historically been the domain of paediatric subspecialties. However, as patients defer surgeries until later in life, providers are needed to help close this emerging clinical care gap for the LGBTQIA+ community.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 6","pages":"330-331"},"PeriodicalIF":14.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-25DOI: 10.1038/s41585-025-01028-4
Yu-Hsiang Lin, Kuo-Jen Lin, Chun-Te Wu
{"title":"Revisiting the complex interactions in nocturnal polyuria: insights on OSA, ADH and ANP","authors":"Yu-Hsiang Lin, Kuo-Jen Lin, Chun-Te Wu","doi":"10.1038/s41585-025-01028-4","DOIUrl":"10.1038/s41585-025-01028-4","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 10","pages":"720-721"},"PeriodicalIF":14.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-25DOI: 10.1038/s41585-025-01027-5
Olaf P. J. Vrooman, Mohammad S. Rahnama’i
{"title":"Reply to ‘Revisiting the complex interactions in nocturnal polyuria: insights on OSA, ADH and ANP’","authors":"Olaf P. J. Vrooman, Mohammad S. Rahnama’i","doi":"10.1038/s41585-025-01027-5","DOIUrl":"10.1038/s41585-025-01027-5","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 10","pages":"722-722"},"PeriodicalIF":14.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1038/s41585-025-01023-9
Sia V. Lindskrog, Trine Strandgaard, Iver Nordentoft, Matthew D. Galsky, Thomas Powles, Mads Agerbæk, Jørgen Bjerggaard Jensen, Catherine Alix-Panabières, Lars Dyrskjøt
Liquid biopsies, indicating the sampling of body fluids rather than solid-tissue biopsies, have the potential to revolutionize cancer care through personalized, noninvasive disease detection and monitoring. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) are promising blood-based biomarkers in bladder cancer. Results from several studies have shown the clinical potential of ctDNA and CTCs in bladder cancer for prognostication, treatment-response monitoring, and early detection of minimal residual disease and disease recurrence. Following successful clinical trial evaluation, assessment of ctDNA and CTCs holds the potential to transform the therapeutic pathway for patients with bladder cancer — potentially in combination with the analysis of urinary tumour DNA — through tailored treatment guidance and optimized disease surveillance. In this Review, the authors provide an overview of circulating tumour DNA and circulating tumour cells as potential biomarkers to provide therapeutic guidance and optimize disease surveillance in bladder cancer. Challenges associated with these biomarkers and future perspectives for clinical implementation are also discussed.
{"title":"Circulating tumour DNA and circulating tumour cells in bladder cancer — from discovery to clinical implementation","authors":"Sia V. Lindskrog, Trine Strandgaard, Iver Nordentoft, Matthew D. Galsky, Thomas Powles, Mads Agerbæk, Jørgen Bjerggaard Jensen, Catherine Alix-Panabières, Lars Dyrskjøt","doi":"10.1038/s41585-025-01023-9","DOIUrl":"10.1038/s41585-025-01023-9","url":null,"abstract":"Liquid biopsies, indicating the sampling of body fluids rather than solid-tissue biopsies, have the potential to revolutionize cancer care through personalized, noninvasive disease detection and monitoring. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) are promising blood-based biomarkers in bladder cancer. Results from several studies have shown the clinical potential of ctDNA and CTCs in bladder cancer for prognostication, treatment-response monitoring, and early detection of minimal residual disease and disease recurrence. Following successful clinical trial evaluation, assessment of ctDNA and CTCs holds the potential to transform the therapeutic pathway for patients with bladder cancer — potentially in combination with the analysis of urinary tumour DNA — through tailored treatment guidance and optimized disease surveillance. In this Review, the authors provide an overview of circulating tumour DNA and circulating tumour cells as potential biomarkers to provide therapeutic guidance and optimize disease surveillance in bladder cancer. Challenges associated with these biomarkers and future perspectives for clinical implementation are also discussed.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 9","pages":"590-608"},"PeriodicalIF":14.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-14DOI: 10.1038/s41585-025-01036-4
Annette Fenner
{"title":"Madrid plays host to a celebration of urology","authors":"Annette Fenner","doi":"10.1038/s41585-025-01036-4","DOIUrl":"10.1038/s41585-025-01036-4","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 5","pages":"253-253"},"PeriodicalIF":14.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-14DOI: 10.1038/s41585-025-01037-3
Annette Fenner
{"title":"Sexual transfer of bacteria for forensic use","authors":"Annette Fenner","doi":"10.1038/s41585-025-01037-3","DOIUrl":"10.1038/s41585-025-01037-3","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 5","pages":"253-253"},"PeriodicalIF":14.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}