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Gagliano-Jucá T, Pencina KM, Shang YV, Travison TG, Lincoff AM, Nissen SE, Artz AS, Li X, Chan A, Patel R, Miller MG, Bhasin S. Association of testosterone-induced increase in neutrophil and monocyte counts with thromboembolic events: The TRAVERSE trial. Am Heart J 2025; 288:77-88. [PMID: 40246046 PMCID: PMC12145252 DOI: 10.1016/j.ahj.2025.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 04/02/2025] [Accepted: 04/05/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND In epidemiological studies, higher leukocyte and platelet counts are associated with increased risk of cardiovascular events. Effects of testosterone replacement therapy (TRT) on leukocyte subsets and platelets in men with hypogonadism and association of circulating leukocyte subtypes and platelets during TRT with cardiovascular events remain unknown. METHODS In the TRAVERSE Trial, 5,204 men, 45-80 years with hypogonadism and preexisting or increased risk of cardiovascular disease (CVD) were randomized to transdermal testosterone or placebo gel daily for up to 5 years. We determined the effect of TRT on neutrophils, monocytes, lymphocytes and platelets and association of changes in leukocyte subtypes and platelets with risk of major adverse cardiovascular (MACE) and venous thromboembolism (VTE) events. RESULTS TRT was associated with significantly greater increase in neutrophils and monocytes, and greater decrease in lymphocytes and platelets than placebo. Changes in neutrophil (odds ratio for 1 SD increase in cell count (OR) 1.32 [1.01, 1.73]) and monocyte (OR 1.39 [1.08, 1.79]) counts were associated with increased risk of VTE, accounting for TRT. Neutrophil and monocyte counts at baseline and on-treatment were also associated with increased risk of MACE, adjusting for treatment (baseline: neutrophils OR 1.18 [1.06,1.31], monocytes OR 1.16 [1.05,1.29]; on-treatment neutrophils: OR 1.25 [1.12, 1.40]; monocytes: OR 1.18 [1.06,1.31]). CONCLUSIONS TRT increased circulating neutrophils and monocytes and decreased lymphocytes and platelets in men with hypogonadism. Changes in monocyte and neutrophil counts were associated with increased risk of VTE. Neutrophil and monocyte counts should be considered when evaluating VTE risk in hypogonadal men treated with TRT. CLINICAL TRIAL REGISTRATION URL:https://clinicaltrials.gov/study/NCT03518034. Unique identifier: NCT03518034. The study was initially registered on March 5, 2018, and the first participant was enrolled on May 23, 2018.
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Affiliation(s)
- Thiago Gagliano-Jucá
- Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| | - Karol M Pencina
- Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Yili V Shang
- Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | - A Michael Lincoff
- Cleveland Clinic Coordinating Center for Clinical Research, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
| | - Steven E Nissen
- Cleveland Clinic Coordinating Center for Clinical Research, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
| | - Andrew S Artz
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
| | - Xue Li
- AbbVie, Inc, North Chicago, IL
| | | | | | | | - Shalender Bhasin
- Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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2
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Zitzmann M, Rastrelli G, Murray RD, Edwards D, Reisman Y, Rao PM, Sahi A, Jones TH, Ferlin A, Armeni E, Corpas E, Cremers JF, David J, Arver S, Antonio L, Corona G. Cardiovascular safety of testosterone therapy-Insights from the TRAVERSE trial and beyond: A position statement of the European Expert Panel for Testosterone Research. Andrology 2025. [PMID: 40372318 DOI: 10.1111/andr.70062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 04/10/2025] [Accepted: 04/29/2025] [Indexed: 05/16/2025]
Abstract
INTRODUCTION Testosterone therapy has become a cornerstone treatment for men with hypogonadism, offering significant benefits such as improved sexual function, mood, muscle mass, and bone density. However, concerns about its cardiovascular safety have historically tempered its use. This position statement synthesizes the current evidence on the cardiovascular safety of testosterone therapy, drawing from key studies including the TRAVERSE trial, other trials, and recent meta-analyses. BACKGROUND AND IMPORTANCE Testosterone therapy aims to restore testosterone levels in men with hypogonadism, a condition associated with increased cardiovascular and metabolic risks. Early research produced mixed results, with some studies suggesting a potential increase in cardiovascular events such as myocardial infarction and stroke, while others indicated possible cardiovascular benefits, particularly in men with coexisting conditions like metabolic syndrome and type 2 diabetes. FINDINGS FROM RECENT STUDIES The TRAVERSE trial, a large-scale, randomized, placebo-controlled study, provided robust evidence that testosterone therapy does not significantly increase the risk of major adverse cardiovascular events. Testosterone therapy was found to effectively mitigate anemia in hypogonadal men, highlighting a dual benefit of increasing red blood cell production while managing cardiovascular risks. The findings from the TRAVERSE trial align with those from previous meta-analyses that concluded that testosterone therapy is safe and does not increase cardiovascular risk. CONSENSUS AND CLINICAL IMPLICATIONS There is consensus that testosterone therapy, when prescribed to appropriately selected patients and monitored regularly, is safe from a cardiovascular standpoint, with the potential benefits outweighing the risks when the therapy is used responsibly. Current guidelines recommend individualized treatment plans with careful monitoring, especially of hematocrit levels. This position statement amalgamates previous knowledge with current data and is in agreement with recent United States Food and Drug Administration label changes for testosterone products.
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Affiliation(s)
- Michael Zitzmann
- Centre for Reproductive Medicine and Andrology, University Hospital of Muenster, Muenster, Germany
| | - Giulia Rastrelli
- Department of Experimental and Clinical Biomedical Sciences, University of Florence
- Andrology and Gender Endocrinology Unit, Careggi Hospital, Florence, Italy
| | - Robert D Murray
- Department of Endocrinology, Leeds Centre for Diabetes & Endocrinology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | - Yacov Reisman
- Sexual Medicine, Flare-Health, Amsterdam, Netherlands
- Center for Sexual Health, Reuth Rehabilitation Hospital, Tel-Aviv, Israel
| | - Preethi Mohan Rao
- Robert Hague Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Trust, Barnsley, UK
- University of Sheffield, Sheffield, UK
| | | | - Thomas Hugh Jones
- Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Alberto Ferlin
- Department of Medicine, University of Padova, Padova, Italy
- Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
| | - Eleni Armeni
- Department of Endocrinology and Diabetes, Royal Free Hospital, London, UK
- School of Health Sciences, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Emiliano Corpas
- Endocrinología del Hospital HLA de Guadalajara
- Endocrinología de la Facultad de Medicina de Alcalá, Madrid, España
| | - Jann-Frederik Cremers
- Centre for Reproductive Medicine and Andrology, University Hospital of Muenster, Muenster, Germany
| | - Janine David
- Porthcawl Medical Centre ,South Wales, Porthcawl, UK
- Princess of Wales Hospital, South Wales, Bridgend, UK
| | - Stefan Arver
- Center for Andrology and Sexual Medicine at Karolinska University Hospital, Stockholm, Sweden
| | - Leen Antonio
- Department of Chronic Diseases and Metabolism, Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
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3
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Liu J, Chin-Yee B, Ho J, Lazo-Langner A, Chin-Yee IH, Iansavitchene A, Hsia CC. Diagnosis, management, and outcomes of drug-induced erythrocytosis: a systematic review. Blood Adv 2025; 9:2108-2118. [PMID: 39913688 PMCID: PMC12051125 DOI: 10.1182/bloodadvances.2024015410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 01/23/2025] [Indexed: 04/25/2025] Open
Abstract
ABSTRACT Secondary erythrocytosis refers to an elevation in hemoglobin or hematocrit due to elevated serum erythropoietin levels. Medications including testosterone and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are increasingly recognized as causes of secondary erythrocytosis. We conducted a systematic review to inform the clinical management of drug-induced erythrocytosis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search in MEDLINE, EMBASE, CENTRAL (all via Ovid), and Google Scholar. Of the 2036 articles screened for eligibility, 45 studies were included in our review, with 35 studies on testosterone and other androgen use, 5 studies on SGLT-2 inhibitors, 3 studies on antiangiogenic tyrosine kinase inhibitors (TKIs), 1 study on erythropoiesis-stimulating agents, and 1 study on a treatment regimen for multidrug-resistant tuberculosis. Cisgender and transgender men on prescription testosterone had erythrocytosis rates of up to 66.7%, with intramuscular formulations, higher doses, and older age associated with increased risk of erythrocytosis. Up to 2.7% of men on testosterone therapy developed thromboembolic events. Among individuals on SGLT-2 inhibitors, erythrocytosis rates ranged from 2.1% to 22%, with those who discontinued therapy demonstrating improvement or resolution of erythrocytosis. Thromboembolic events were reported in up to 10% of these individuals. Antiangiogenic TKIs were studied in patients with cancer, with erythrocytosis developing in up to 43.5% of patients. Drug-induced erythrocytosis is a heterogeneous condition for which there is no clear consensus among clinicians about its diagnosis and management. We offer recommendations for clinical practice within the scope of this systematic review, although further research is required.
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Affiliation(s)
- Jessica Liu
- Department of Medicine, London Health Sciences Centre, London, ON, Canada
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Benjamin Chin-Yee
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada
- Department of History and Philosophy of Science, University of Cambridge, Cambridge, United Kingdom
| | - Jenny Ho
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada
| | - Alejandro Lazo-Langner
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada
| | - Ian H. Chin-Yee
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada
| | - Alla Iansavitchene
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Health Science Library, London Health Sciences Centre, London, ON, Canada
| | - Cyrus C. Hsia
- Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
- Division of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, Canada
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4
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Biernikiewicz M, Rusiecka A, Kałka D. Obesity and sexual desire: a systematic review and meta-analysis. J Sex Med 2025; 22:677-693. [PMID: 40163679 DOI: 10.1093/jsxmed/qdaf057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 02/23/2025] [Accepted: 02/26/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Impaired sexual functioning is one of the consequences of obesity with hormonal disorders involving testosterone. AIM To explore the link between obesity and sexual desire, to assess how changes in body weight affect sexual desire, and to examine the role of testosterone in these changes in obese and overweight men. METHODS The systematic review was conducted in PubMed. Studies involving obese/overweight men that reported different libido levels or changes after weight loss interventions were included. Meta-analysis and meta-regression were performed. RESULTS The search identified 2259 studies, of which 28 met the eligibility criteria. Most studies focused on weight-loss interventions (n = 21, 77%), with 13 studies investigating the effect of bariatric surgeries. Testosterone levels were reported in 14 studies. The studies encompassed a total population of 18 653 people, including 10 356 obese and overweight men. Of the 28 identified studies, 15 indicated a potential association between BMI, waist circumference, and sexual desire. Effect size meta-analysis (calculated using data from four studies presenting results before and after bariatric surgery) suggests that an increase in the International Index of Erectile Function sexual desire domain was very strongly associated with changes in a patients' weight resulting from bariatric surgery (d = 1.22, 95% CI 0.41-2.03, P = 0.003). The meta-analysis of four studies, presenting results before and after diet intervention, showed a strong impact of weight loss on an increase of the Sexual Desire Inventory (SDI), (d = 1.16, 95% CI 0.44-1.88, P = 0.002) The meta-regression revealed a significant association between the level of sexual desire on the SDI and the magnitude of BMI changes before and after dieting interventions (R2 = 77.97%; P = 0.002). The meta-analysis of plasma total testosterone levels from studies that present results before and after selected diets showed a strong impact of diet on the increase in testosterone levels after interventions (d = 1.39 95% CI 0.86-1.92; P < 0.001). There was a significant impact of the level of plasma total testosterone on the variance of sexual desire in the SDI questionnaire (R2 = 5.33%; P < 0.001). LIMITATIONS OF EVIDENCE A lack of studies that focus on sexual desire in obesity, the heterogeneity of the included population, the variability in the used questionnaires and reported statistics. CONCLUSIONS A potential association between sexual desire and body weight exists. Weight loss interventions, including dietary changes and bariatric surgery, significantly increased both sexual desire and plasma total testosterone levels. Additionally, variations in plasma total testosterone levels had a significant effect on the variability of sexual desire in obese men.
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Affiliation(s)
| | - Agnieszka Rusiecka
- Statistical Analysis Centre, Wroclaw Medical University, 50-368 Wrocław, Poland
| | - Dariusz Kałka
- Men's Health Centre in Wrocław, 54-154 Wrocław, Poland
- Faculty of Physiotherapy, Wroclaw University of Health and Sport Sciences, 51-612 Wrocław, Poland
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5
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Naelitz BD, Momtazi-Mar L, Vallabhaneni S, Cannarella R, Vij SC, Parekh NV, Bole R, Lundy SD. Testosterone replacement therapy and spermatogenesis in reproductive age men. Nat Rev Urol 2025:10.1038/s41585-025-01032-8. [PMID: 40346275 DOI: 10.1038/s41585-025-01032-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2025] [Indexed: 05/11/2025]
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.
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Affiliation(s)
- Bryan D Naelitz
- Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA.
| | - Leila Momtazi-Mar
- Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA
- Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA
| | | | - Rossella Cannarella
- Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Sarah C Vij
- Urology Section, Division of Surgical Subspecialties, University of Texas Health Austin, Austin, TX, USA
| | - Neel V Parekh
- Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Raevti Bole
- Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Scott D Lundy
- Department of Urology, Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA
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6
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Liu C, Peng H, Yu J, Luo P, Xiong C, Chen H, Fan H, Ma Y, Ou W, Zhang S, Yang C, Zhao L, Zhang Y, Guo X, Ke Q, Wang T, Deng C, Li W, Xiang AP, Xia K. Impaired ketogenesis in Leydig Cells drives testicular aging. Nat Commun 2025; 16:4224. [PMID: 40328805 PMCID: PMC12056170 DOI: 10.1038/s41467-025-59591-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 04/17/2025] [Indexed: 05/08/2025] Open
Abstract
Testicular aging commonly leads to testosterone deficiency and impaired spermatogenesis, yet the underlying mechanisms remain elusive. Here, we show that Leydig cells are particularly vulnerable to aging processes in testis. Single-cell RNA sequencing identifies the expression of Hmgcs2, the gene encoding rate-limiting enzyme of ketogenesis, decreases significantly in Leydig cells from aged mice. Additionally, the concentrations of ketone bodies β-hydroxybutyric acid and acetoacetic acid in young testes are substantially higher than that in serum, but significantly diminish in aged testes. Silencing of Hmgcs2 in young Leydig cells drives cell senescence and accelerated testicular aging. Mechanistically, β-hydroxybutyric acid upregulates the expression of Foxo3a by facilitating histone acetylation, thereby mitigating Leydig cells senescence and promoting testosterone production. Consistently, enhanced ketogenesis by genetic manipulation or oral β-hydroxybutyric acid supplementation alleviates Leydig cells senescence and ameliorates testicular aging in aged mice. These findings highlight defective ketogenesis as a pivotal factor in testicular aging, suggesting potential therapeutic avenues for addressing age-related testicular dysfunction.
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Grants
- This work was supported by National Key Research and Development Program of China(2022YFA1104100), National Natural Science Foundation of China (82430050, 32130046, 82371611, 82371609, 82171564, 82101669, 82301847, 82171617, 82301796), Key Research and Development Program of Guangdong Province (2019B020235002), Natural Science Foundation of Guangdong Province (2022A1515010371), Guangdong Basic and Applied Basic Research Foundation (2021A1515010377), Key Scientific and Technological Program of Guangzhou City (2023B01J1002), Pioneering talents project of Guangzhou Development Zone (2021-L029), China Postdoctoral Science Foundation (2023M733656), Shenzhen Nanshan District Health System Science and Technology Major Project (NSZD2023049), Sanming Project of Medicine in Shenzhen Nanshan (SZSM202103012).
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Affiliation(s)
- Congyuan Liu
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hao Peng
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jiajie Yu
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Peng Luo
- Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, The Key Laboratory for Reproductive Medicine of Guangdong Province, Guangzhou, Guangdong, China
| | - Chuanfeng Xiong
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hong Chen
- Center for Stem Cells Translational Medicine, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China
- Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Hang Fan
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yuanchen Ma
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wangsheng Ou
- State Key Laboratory of Ophthalmology, Zhong Shan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Suyuan Zhang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Cuifeng Yang
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Lerong Zhao
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yuchen Zhang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaolu Guo
- Center for Stem Cells Translational Medicine, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China
- Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
| | - Qiong Ke
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Tao Wang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chunhua Deng
- Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Weiqiang Li
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Andy Peng Xiang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
| | - Kai Xia
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
- National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
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7
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Arun AS, Durant TJS, El-Khoury JM, Krumholz HM. Reevaluating the Threshold for Low Total Testosterone. Clin Chem 2025; 71:609-611. [PMID: 40238540 DOI: 10.1093/clinchem/hvaf025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/25/2025] [Indexed: 04/18/2025]
Affiliation(s)
- Adith S Arun
- Yale School of Medicine, New Haven, CT, United States
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, United States
| | - Thomas J S Durant
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, United States
- Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, CT, United States
| | - Joe M El-Khoury
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, United States
| | - Harlan M Krumholz
- Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, United States
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States
- Department of Health Policy and Management, Yale School of Public Health, New Haven, CT, United States
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8
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Pagadala MS, Teerlink CC, Jasuja GK, Palnati M, Anglin-Foote T, Chang NCN, Deka R, Lee KM, Agiri FY, Amariuta T, Seibert TM, Rose BS, Pridgen KM, Lynch JA, Carter HK, Panizzon MS, Hauger RL. Discovery of novel ancestry specific genes for androgens and hypogonadism in Million Veteran Program Men. Nat Commun 2025; 16:4104. [PMID: 40316537 PMCID: PMC12048691 DOI: 10.1038/s41467-025-57372-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 02/12/2025] [Indexed: 05/04/2025] Open
Abstract
Given the various roles of testosterone in men's health, we conducted a multi-ancestral genetic analysis of total testosterone, free testosterone, SHBG, and hypogonadism in men within the Million Veteran Program (MVP). Here we identified 157 significant testosterone genetic variants, of which 8 have significant ancestry-specific associations. These variants implicate several genes, including SERPINF2, PRPF8, BAIAP2L1, SHBG, PRMT6, and PPIF, related to liver function. Genetic regulators of testosterone have cell type-specific effects in the testes, liver, and adrenal gland and are associated with disease risk. We conducted a meta-analysis amongst ancestry groups to identify 188 variants significantly associated with testosterone, of which 22 are novel associations. We constructed genetic scores for total testosterone, SHBG levels, and hypogonadism and find that men with higher testosterone genetic scores have lower odds of diabetes, hyperlipidemia, gout, and cardiac disorders. These findings provide insight into androgen regulation and identify novel variants for disease risk stratification.
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Affiliation(s)
- Meghana S Pagadala
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
- Medical Scientist Training Program, University of California San Diego, La Jolla, CA, USA
- Biomedical Science Program, University of California San Diego, La Jolla, CA, USA
| | - Craig C Teerlink
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
- Department of Internal Medicine, Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, US
| | - Guneet K Jasuja
- Center for Healthcare Organization and Implementation Research (CHOIR), VA Bedford Healthcare System, Bedford, MA, US
- Section of General Internal Medicine, Boston University School of Medicine, Boston, MA, US
- Department of Health Law, Policy, and Management, Boston University School of Public Health, Boston, MA, US
| | - Madhuri Palnati
- Center for Healthcare Organization and Implementation Research (CHOIR), VA Bedford Healthcare System, Bedford, MA, US
| | - Tori Anglin-Foote
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
| | - Nai-Chung N Chang
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
| | - Rishi Deka
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
| | - Kyung M Lee
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
| | - Fatai Y Agiri
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
| | - Tiffany Amariuta
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
- Halicioglu Data Science Institute, University of California San Diego, La Jolla, CA, USA
| | - Tyler M Seibert
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
- Department of Radiology, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
| | - Brent S Rose
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
- Department of Urology, University of California San Diego, La Jolla, CA, USA
| | - Kathryn M Pridgen
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
| | - Julie A Lynch
- VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Healthcare System, Salt Lake City, UT, US
- Department of Internal Medicine, Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT, US
| | - Hannah K Carter
- Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Matthew S Panizzon
- Research Service, VA San Diego Healthcare System, San Diego, CA, USA
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA
- Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA
| | - Richard L Hauger
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
- Center for Behavior Genetics of Aging, University of California San Diego, La Jolla, CA, USA.
- Center of Excellence for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, San Diego, CA, USA.
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9
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Vauhkonen PK, Haukka J, Vauhkonen I, Lindroos KM, Mäyränpää MI. Predicting Anabolic Androgenic Steroid Doping among Specialized Health Care Patients with Elastic Net Regression Reveals Potential Laboratory Variables for "Patient Biological Passport". SPORTS MEDICINE - OPEN 2025; 11:46. [PMID: 40310581 PMCID: PMC12045897 DOI: 10.1186/s40798-025-00854-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 04/16/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND Recent years have brought significant development in athlete doping use detection with the implementation of the Athlete Biological Passport (ABP). The aim of this study was to explore if similar methods could also be used to detect non-medical use of anabolic androgenic steroids (AAS) among clinical patients. For this purpose, six elastic net regression models were trained in a sample of Finnish specialized health care male patients (N = 2918; no doping = 1911, AAS doping = 1007), using different approaches to longitudinal laboratory measurements as predictive variables. The laboratory data was retrieved from the Hospital District of Helsinki and Uusimaa (HUS) data lake, and doping use status was defined by patient disclosure, recorded in digital medical record free texts. Length of observation time (e.g., time between the first and last laboratory measurement) was used as weight. Model performance was tested with holdout cross-validation. RESULTS All the tested models showed promising discriminative ability. The best fit was achieved by using the existence of out-of-reference range measurements of 31 laboratory parameters as predictors of AAS doping, with test data area under the receiver operating characteristic curve (AUC) of 0.757 (95% CI 0.725-0.789). CONCLUSIONS The findings of this preliminary study suggest that AAS doping could be detected in clinical context using real-life longitudinal laboratory data. Further model development is encouraged, with added dimensions regarding the use of different AAS substances, length of doping use, and other background data that may further increase the diagnostic accuracy of these models.
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Affiliation(s)
- Paula Katriina Vauhkonen
- Department of Forensic Medicine, University of Helsinki, Haartmaninkatu 3, P.O. Box 63, Helsinki, FI-00014, Finland.
- Finnish Institute for Health and Welfare, Forensic Medicine unit, Mannerheimintie 166, P.O. Box 30, Helsinki, FI-00271, Finland.
| | - Jari Haukka
- Finnish Institute for Health and Welfare, Forensic Medicine unit, Mannerheimintie 166, P.O. Box 30, Helsinki, FI-00271, Finland
- Department of Public Health, University of Helsinki, Tukholmankatu 8 B, P.O. Box 20, Helsinki, FI-00014, Finland
| | - Ilkka Vauhkonen
- Novo Nordisk Farma Oy, Linnoitustie 6, Espoo, FI-02600, Finland
| | - Katarina Mercedes Lindroos
- Finnish Institute for Health and Welfare, Forensic Medicine unit, Mannerheimintie 166, P.O. Box 30, Helsinki, FI-00271, Finland
| | - Mikko Ilari Mäyränpää
- Department of Pathology, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, Helsinki, FI-00014, Finland
- Helsinki University Hospital, Diagnostic center, pathology, P.O. Box 340, Helsinki, FI-00029, Finland
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10
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Salvio G, Balercia G, Kadioglu A. Hypogonadotropic hypogonadism as a cause of NOA and its treatment. Asian J Androl 2025; 27:322-329. [PMID: 39513636 DOI: 10.4103/aja202483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 08/19/2024] [Indexed: 11/15/2024] Open
Abstract
ABSTRACT Hypogonadotropic hypogonadism (HH) represents a relatively rare cause of nonobstructive azoospermia (NOA), but its knowledge is crucial for the clinical andrologists, as it represents a condition that can be corrected with medical therapy in 3 quarters of cases. There are forms of congenital HH, whether or not associated with an absent sense of smell (anosmic HH or Kallmann syndrome, and normosmic HH, respectively), and forms of acquired HH. In congenital HH, complete absence of pubertal development is characteristic. On the other hand, if the deficit occurs after the time of pubertal development, as in acquired HH patients, infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance. Gonadotropin-releasing hormone (GnRH) or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results, although a small but significant proportion of patients do not achieve sufficient responses.
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Affiliation(s)
- Gianmaria Salvio
- Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, Italy
| | - Giancarlo Balercia
- Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, Italy
| | - Ates Kadioglu
- Section of Andrology, Department of Urology, Istanbul School of Medicine, Istanbul 34093, Türkiye
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11
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McMahon A, Fantus RJ. Testosterone Replacement Therapy for Testosterone Deficiency in Older Men. Clin Geriatr Med 2025; 41:163-173. [PMID: 40345771 DOI: 10.1016/j.cger.2025.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/11/2025]
Abstract
This review explores the increasing use of testosterone therapy in aging men, driven by the need to address age-related symptoms like decreased libido, muscle weakness, and anemia. Studies such as the Testosterone Trials and Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men trial show that testosterone therapy can offer benefits in sexual function, physical performance, and bone density, with no significant increase in risks for cardiovascular events or prostate cancer. However, conflicting data suggest that careful, individualized treatment is necessary, especially in older men with existing health conditions.
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Affiliation(s)
- Amber McMahon
- Department of Urology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
| | - Richard J Fantus
- Department of Urology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
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12
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Aleksova J, Ebeling P, Elder G. The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease. Nat Rev Endocrinol 2025; 21:301-313. [PMID: 39820573 DOI: 10.1038/s41574-024-01083-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 01/19/2025]
Abstract
Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.
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MESH Headings
- Humans
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/physiopathology
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 1/complications
- Diabetes Mellitus, Type 1/physiopathology
- Diabetes Mellitus, Type 1/metabolism
- Renal Insufficiency, Chronic/complications
- Renal Insufficiency, Chronic/physiopathology
- Renal Insufficiency, Chronic/metabolism
- Fractures, Bone/etiology
- Bone and Bones/metabolism
- Bone and Bones/physiopathology
- Bone Density/physiology
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Affiliation(s)
- Jasna Aleksova
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
- Hudson Institute for Medical Research, Clayton, Victoria, Australia.
- Department of Endocrinology, Monash Health, Clayton, Victoria, Australia.
| | - Peter Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia
- Department of Endocrinology, Monash Health, Clayton, Victoria, Australia
| | - Grahame Elder
- Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia
- Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
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13
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Hashimi MA, Pinggera GM, Shah R, Agarwal A. Clinician's guide to the management of azoospermia induced by exogenous testosterone or anabolic-androgenic steroids. Asian J Androl 2025; 27:330-341. [PMID: 39820213 DOI: 10.4103/aja2024104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 10/16/2024] [Indexed: 01/19/2025] Open
Abstract
ABSTRACT Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
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Affiliation(s)
- Manaf Al Hashimi
- Global Andrology Forum, 130 West Juniper Lane, Moreland Hills, OH 44022, USA
- Department of Urology, Burjeel Hospital-Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Germar-Michael Pinggera
- Global Andrology Forum, 130 West Juniper Lane, Moreland Hills, OH 44022, USA
- Department of Urology, Innsbruck Medical University, Innsbruck 6020, Austria
| | - Rupin Shah
- Global Andrology Forum, 130 West Juniper Lane, Moreland Hills, OH 44022, USA
- Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, Maharashtra 400050, India
| | - Ashok Agarwal
- Global Andrology Forum, 130 West Juniper Lane, Moreland Hills, OH 44022, USA
- Cleveland Clinic, Cleveland, OH 44195, USA
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14
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Miner M, Wang C, Kaminetsky J, Khera M, Goldstein I, Carson C, Chidambaram N, King S, Dobs A. Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism. Andrology 2025; 13:882-893. [PMID: 39252657 PMCID: PMC12006877 DOI: 10.1111/andr.13747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 07/25/2024] [Accepted: 08/14/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. OBJECTIVE The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). MATERIALS AND METHODS In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted by 75 mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140 ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. RESULTS Overall mean ± SD baseline testosterone was 205.7 ± 71.6 ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91 vs. -0.10; p = 0.035), and mental component summary (3.82 vs. 0.55; p = 0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57 vs. -0.20; p = 0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. DISCUSSION AND CONCLUSION Male patients with hypogonadism receiving oral testosterone undecanoate 225 mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.
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Affiliation(s)
- Martin Miner
- Men's Health CenterMiriam HospitalProvidenceRhode IslandUSA
| | - Christina Wang
- Clinical and Translational Science InstituteThe Lundquist Institute at Harbor‐UCLA Medical CenterTorranceCaliforniaUSA
| | | | | | | | - Culley Carson
- University of North Carolina at Chapel HillChapel HillNorth CarolinaUSA
| | | | | | - Adrian Dobs
- Johns Hopkins University School of MedicineBaltimoreMarylandUSA
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15
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Percik R, Vered S, Liel Y. Incidence, Temporal Trends, and Socioeconomic Aspects of Acquired Male Hypogonadism. Exp Clin Endocrinol Diabetes 2025; 133:228-234. [PMID: 40068908 DOI: 10.1055/a-2556-2844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
Little is known about temporal trends in the incidence of male hypogonadism and its correlation with socioeconomic status, which we examined in the present study.Data were extracted from the Maccabi Health Services computerized database between 2001-2017. The study population included 4,261 men aged 21 to 80 years with biochemically proven hypogonadism defined and classified according to the European Male Aging Study criteria. Patients on testosterone or testosterone-modifying drugs were excluded. The socioeconomic status was assessed based on verified financial data pertinent to the area of residence.The incidence of male hypogonadism increased with age in all the socioeconomic strata. Among the hypogonadal men, 75% had hypogonadotropic hypogonadism. The overall incidence of hypogonadism increased 1.4-fold between the 2001-2009 and 2010-2017 periods [from 41.7 (39.7-43.8) to 58.5 (56.4-60.8) per 100,000 person-years) (95% CI)], mainly due to an increase in hypogonadotropic hypogonadism. The temporal increase in hypogonadotropic hypogonadism occurred in all age groups and all socioeconomic strata but was notably more prominent in >51-year age groups of the more affluent socioeconomic strata. The mean body mass index remained unchanged throughout the study period.A temporal increase was observed in male hypogonadism, mainly hypogonadotropic hypogonadism, corresponding with previously observed temporal decreases in testosterone levels in men. This trend could be possibly partly attributed to an underappreciated increase in mental distress due to decreasing global happiness indices, increasing stress, and occupational burnout in specific occupations associated with more affluent populations (i.e., high-tech, finance, medical). This preliminary proposition deserves further investigation.
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Affiliation(s)
- Ruth Percik
- Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center at Tel Hashomer, Tel Hashomer, Israel
- Research Program, Maccabi Institute for Health Services Research, Tel Aviv, Israel
| | - Shiraz Vered
- School of Public Health, University of Haifa, Haifa, Israel
| | - Yair Liel
- Research Program, Maccabi Institute for Health Services Research, Tel Aviv, Israel
- Faculty of Medicine, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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16
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Cai L, Xie H, Li W, Chen C, Li T, Xu L, Mao Y, Liang J, Wen J, Chen G. Exploring the non-linear association and threshold effect of sedentary behavior on testosterone deficiency. Endocrine 2025; 88:638-649. [PMID: 40016569 DOI: 10.1007/s12020-025-04199-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 02/14/2025] [Indexed: 03/01/2025]
Abstract
BACKGROUND Sedentary behavior has emerged as a potential risk factor for various health issues, including hormonal imbalances like testosterone deficiency (TD). However, the relationship between sedentary time and TD remains underexplored, especially with respect to the complex biological mechanisms underlying this association. This study aimed to examine the association between sedentary time and TD in adult males. METHODS This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey 2011-2016. A total of 6057 male participants aged 20 years and older were included. Sedentary time was categorized into quartiles, and TD was defined as serum testosterone levels below 300 ng/dL. Logistic regression models were employed to assess the association between sedentary time and TD, adjusting for demographic, lifestyle, and health-related covariates. Restricted cubic spline (RCS) analysis and segmented regression were also conducted to explore potential non-linear relationships and thresholds. Subgroup analyses were performed to examine the consistency of associations across various groups. RESULTS The analysis revealed a significant positive association between sedentary time and TD. Prolonged sedentary behaviour was consistently associated with higher odds of TD across all models (all p < 0.001). RCS analysis showed a significant non-linear relationship, particularly as sedentary time exceeded 4.5 h per day, with a marked increase in the likelihood of TD (p-non-linear = 0.027). Subgroup analysis indicated that this association was most pronounced in Non-Hispanic Whites, current smokers, and drinkers, and was weaker in individuals with diabetes, where the association lost statistical significance after full adjustment. CONCLUSIONS This study identifies a significant association between prolonged sedentary behaviour and a higher risk of TD, suggesting that sedentary behavior may play a key role in the development of TD, particularly in specific high-risk populations.
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Affiliation(s)
- Liangchun Cai
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
| | - Haiping Xie
- Department of Rheumatology and Immunology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Wue Li
- Department of Emergency, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
- Fujian Provincial Key Laboratory of Emergency Medicine, Fujian Provincial Institute of Emergency Medicine, Fujian Emergency Medical Center, Fuzhou, China
| | - Chuhui Chen
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Ting Li
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Lizhen Xu
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Yaqian Mao
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Jixing Liang
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Junping Wen
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
| | - Gang Chen
- Department of Endocrinology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
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17
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Yeap BB, Tran C, Douglass CM, McNeil JJ. Testosterone Therapy in Older Men: Present and Future Considerations. Drugs Aging 2025:10.1007/s40266-025-01209-1. [PMID: 40287898 DOI: 10.1007/s40266-025-01209-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2025] [Indexed: 04/29/2025]
Abstract
Testosterone is the classical male anabolic hormone, involved in sexual development, virilisation and regulation of body composition in adult men. Organic disease involving the hypothalamus, pituitary or testes may interfere with endogenous testosterone production. In such men, testosterone treatment effectively ameliorates symptoms and signs of androgen deficiency. However, non-gonadal factors including age, body mass index and medical comorbidities influence circulating testosterone, and older men have on average lower testosterone concentrations compared with younger men. In these men, testosterone treatment would be a pharmacological intervention requiring stringent justification via high-quality evidence from randomised controlled trials (RCTs). Recent RCTs show benefits of testosterone treatment to improve sexual function, anaemia and bone mineral density in older men, and to prevent or revert type 2 diabetes mellitus in men at high risk. Results from a large cardiovascular safety trial in men with or at risk of cardiovascular disease provide important reassurance as to cardiovascular and prostate safety of testosterone treatment. Key questions remain as to whether testosterone's anabolic and other effects can be used safely to counter reductions in lean mass associated with incretin-based weight loss medications in men with obesity, and whether it might prevent disabilities including frailty, osteoporotic fractures and dementia in older men generally. This last question could be answered by a new testosterone RCT, targeting men in the 65-80 years age bracket, which would necessarily be large and of extended duration. A composite endpoint could be used which integrates potential benefits and risks, such as disability-free survival.
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Affiliation(s)
- Bu B Yeap
- Medical School, University of Western Australia, Perth, Australia.
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Australia.
| | - Cammie Tran
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
| | | | - John J McNeil
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
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18
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Tong L, Chen G. Correlation between pan immune inflammation value and testosterone deficiency risk increase. Sci Rep 2025; 15:13632. [PMID: 40254668 PMCID: PMC12009990 DOI: 10.1038/s41598-025-98517-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 04/11/2025] [Indexed: 04/22/2025] Open
Abstract
Testosterone deficiency seriously affects male reproductive function, growth and development, and quality of life. There is a certain association between inflammation and testosterone. PIV, a novel immune-inflammatory biomarker, has emerged. However, little is known about the relationship between PIV and serum testosterone. This study aims to investigate the relationship between PIV and serum testosterone. In this cross-sectional study, we analyzed data from 7389 participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. Serum total testosterone levels were measured using precise isotope dilution liquid chromatography and tandem mass spectrometry. PIV was calculated as (neutrophil count × monocyte count × platelet count)/lymphocyte count. Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the PIV and testosterone deficiency. Using PIV Quartile 1 as the reference, in the fully adjusted model, the odds ratios (OR) and 95% confidence intervals (CI) for Quartile 2 to Quartile 4 participants were 1.14 (0.93, 1.40), 1.28 (0.99, 1.65), and 1.51 (1.18, 1.95), respectively (P for trend < 0.001), with participants in the highest quartile of PIV having a 51% increased risk of testosterone deficiency compared to those in the lowest quartile of PIV. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between PIV and testosterone deficiency, with a turning point at 565.89. The subgroup analysis results showed that, except for obesity, there was no statistically significant difference in the relationship between PIV and testosterone deficiency among different subgroups (P > 0.05). Our study results indicate a positive correlation between PIV and the risk of testosterone deficiency. This suggests that PIV may serve as a potential indicator for testosterone deficiency.
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Affiliation(s)
- Ling Tong
- Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Gang Chen
- Department of Laboratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China.
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19
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Leśniak K, Lubas A, Niemczyk S. The Usefulness of Testosterone in Saliva Tests to Detect Testosterone Deficiency in Men with Advanced Chronic Kidney Disease: A Single-Center Study. J Clin Med 2025; 14:2818. [PMID: 40283649 PMCID: PMC12027738 DOI: 10.3390/jcm14082818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Revised: 04/15/2025] [Accepted: 04/17/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to serum testosterone. This study aimed to assess the usefulness of determining free testosterone concentration in saliva to detect testosterone deficiency in men with advanced CKD, including those on dialysis. Methods: A total of 77 adult, male patients (aged 41-89 years old)-30 with CKD stage G3-G4, 30 on hemodialysis (HD), and 17 on peritoneal dialysis (PD)-were evaluated. The concentration of free testosterone was determined in saliva (SalFT), while the concentration of total testosterone (TT) was determined in blood serum. Serum-free testosterone levels were calculated (cFT). Results: SalFT did not differ from cFT in the CKD (p = 0.547) and PD groups (p = 0.409). In the HD group, SalFT was higher than cFT (p = 0.009). SalFT was positively correlated with cFT (r = 0.435 in the CKD and r = 0.479 in the HD) and TT (r = 0.451 in CKD), but only in the group of patients with SalFT levels below 140 pg/mL and 120 pg/mL, respectively. A cut-off value of SalFT ≤ 60.6 pg/mL showed 73.9% sensitivity and 77.8% specificity for testosterone deficiency recognition. Conclusions: Our study supports the value of SalFT measurement as a non-invasive approach in the diagnosis of testosterone deficiency in men with advanced CKD, as well as patients on hemodialysis.
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Affiliation(s)
- Ksymena Leśniak
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine—National Research Institute, Szaserów Street 128, 04-141 Warsaw, Poland; (A.L.); (S.N.)
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20
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Fink J, Bentzen K, Horie S. Management of hematocrit levels for testosterone replacement patients, a narrative review. Sex Med Rev 2025; 13:229-236. [PMID: 40126900 DOI: 10.1093/sxmrev/qeaf013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 02/01/2025] [Accepted: 02/27/2025] [Indexed: 03/26/2025]
Abstract
INTRODUCTION Testosterone replacement therapy is gaining more and more popularity among hypogonadal men. The positive effects on body composition, metabolic functions, and mental well-being can improve the quality of life of many men. However, testosterone can also trigger several side effects, including increases in hematocrit and hemoglobin levels. Exogenous testosterone tends to increase erythropoiesis. The testosterone-induced increase in red blood cells can increase performance via improved transport of oxygen to the body. However, red blood cell overproduction can cause blood clots and severe sequelae such as heart attack, stroke, or pulmonary embolism. These side effects need to be closely monitored in testosterone replacement therapy (TRT) patients. Traditionally, cessation of TRT was recommended for patients with severe polycythemia. However, cessation of TRT can lead to the recurrence of symptoms experienced before TRT. Fortunately, recent innovations in testosterone preparations allow a treatment with less side effects on hematocrit levels. OBJECTIVES This review focuses on highlighting novel methods to treat hypogonadism while minimizing side effects related to hematocrit levels. METHODS We identified relevant articles using PubMed and Google Scholar searching for specific terms from 2000-2024. RESULTS Elevations in hematocrit levels triggered by testosterone therapy seem to be controversial, some studies advocate noninferior effects as compared to placebo while others found adverse side effects on cardiovascular health. However, the way of administration of testosterone seems to strongly influence the extent of hematocrit increases and can therefore be minimized by choosing the right testosterone preparation. CONCLUSION Depending on the route of administration, testosterone replacement therapy can lead to significant increases in hematocrit and potential cardiovascular incidents. On the other hand, for hypogonadal patients with anemia, testosterone replacement therapy might be beneficial not only for restoring healthy testosterone levels but also red blood cells.
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Affiliation(s)
- Julius Fink
- Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo 113 8421, Japan
- Department of Kinesiology, Occidental College, Los Angeles, CA 90041, United States
| | - Kirk Bentzen
- Department of Kinesiology, Occidental College, Los Angeles, CA 90041, United States
| | - Shigeo Horie
- Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo 113 8421, Japan
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21
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Soares MR, de Carvalho RM, Dos Santos Cirino H, Martins R, Miranda Furtado CL, Santana BAA, Calado RT, Ferriani RA, Dos Reis RM. Effect of SARS-CoV-2 infection on sperm telomere length. J Assist Reprod Genet 2025; 42:1167-1175. [PMID: 39934464 PMCID: PMC12055711 DOI: 10.1007/s10815-025-03408-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 01/18/2025] [Indexed: 02/13/2025] Open
Abstract
PURPOSE The repercussions and outcomes of the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns about potential adverse effects on the male reproductive system. Telomeres are crucial in maintaining the integrity and stability of genomic DNA, and viral infections can induce changes in telomere biology. In this study, the repercussions of SARS-CoV-2 infection in male reproductive health were analyzed. METHODS This case-control study enrolled subjects who donated blood and semen samples. Fifty-six men with and 56 without prior COVID-19 infection, ages 18-45 years, were included. Semen analysis and hormonal levels were evaluated. The presence of SARS-CoV-2 RNA in semen and the sperm telomere length were assessed by quantitative polymerase chain reaction and associated with clinical and laboratory data. To reduce interference factors, known variables that influence telomere length were analyzed independently. RESULTS Sperm telomere length was significantly diminished in the COVID-19 positive group with a mean difference of 0.635 compared to the negative group (p = 0.041). Most individuals in the COVID-19 positive group were clinically classified as asymptomatic/mild illness, and all samples were collected more than 90 days after recovery. No statistically significant differences were observed between the groups in terms of clinical data, semen parameters, and serum levels of follicle-stimulation hormone, estradiol, and testosterone. Persistent or subgenomic SARS-CoV-2 RNA was not detected in the semen samples. CONCLUSION This study revealed that SARS-CoV-2 infection reduced sperm telomere length without alterations in semen parameters or hormonal levels. These results provide further evidence that SARS-CoV-2 infection can induce genomic alterations in human sperm.
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Affiliation(s)
- Murilo Racy Soares
- Human Reproduction Center, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Roberto Marins de Carvalho
- Human Reproduction Center, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Heithor Dos Santos Cirino
- Human Reproduction Center, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Ronaldo Martins
- Center for Virology Research, Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Cristiana Libardi Miranda Furtado
- Graduate Program in Medical Sciences, Experimental Biology Center, Universidade de Fortaleza, Fortaleza, Ceará, Brazil
- Drug Research and Development Center, Postgraduate Program in Translational Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Bárbara Amélia Aparecida Santana
- Department of Medical Images, Hematology and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Rodrigo Tocantins Calado
- Department of Medical Images, Hematology and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Rui Alberto Ferriani
- Human Reproduction Center, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Rosana Maria Dos Reis
- Human Reproduction Center, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
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22
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Fritz AA, Reinert JP. Efficacy and Safety of Testosterone Replacement in Testicular Cancer Survivors With Treatment-Influenced Hypogonadism: A Systematic Review. Ann Pharmacother 2025; 59:337-349. [PMID: 39250190 DOI: 10.1177/10600280241278786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2024] Open
Abstract
OBJECTIVE The objective is to evaluate the efficacy and safety of testosterone supplementation in testicular cancer survivors with treatment-related hypogonadism. DATA SOURCES This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and used Embase, PubMed/MEDLINE, Cochrane Central, Web of Science Core Collection, Korean Journal Index, SciELO, and Global Index Medicus to obtain data in June of 2024. STUDY SELECTION AND DATA EXTRACTION Analyses evaluating testosterone supplementation in testicular cancer survivors with treatment-induced hypogonadism were included. Any analyses not assessing supplementation in this population or deemed unretrievable were excluded. DATA SYNTHESIS Ten analyses were included for analysis. A total of 332 bilateral or unilateral testicular cancer survivors with treatment-influenced hypogonadism were reviewed, with 238 patients receiving testosterone replacement. Eight of the 10 analyses assessed participants without poor quality-of-life (QOL) metrics, metabolic factors, and bone mineral density (BMD) at baseline and only found a significant benefit in fat distribution metrics with testosterone supplementation. Two analyses evaluated participants with poor QOL metrics or BMD at baseline and showed improvements in QOL or BMD with testosterone supplementation. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE There is robust evidence regarding the efficacy and safety of testosterone replacement in hypogonadal individuals but limited evidence specifically evaluating supplementation in testicular cancer survivors with treatment-influenced hypogonadism. CONCLUSIONS The results suggest testosterone replacement may be beneficial in patients with impaired QOL metrics, metabolic factors, and BMD at baseline; the results also suggest that routine supplementation for all individuals in this patient population lacks efficacy.
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Affiliation(s)
- Andrew A Fritz
- College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH, USA
| | - Justin P Reinert
- College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH, USA
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23
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Ferrarese A, Hurtado Díaz de León I, Tapper EB, Burra P. Sexual health and function in liver disease. Hepatol Commun 2025; 9:e0691. [PMID: 40178496 PMCID: PMC11970893 DOI: 10.1097/hc9.0000000000000691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 02/25/2025] [Indexed: 04/05/2025] Open
Abstract
Sex is a central aspect of human life and is significantly impacted by chronic illness. Cirrhosis, due to its unique pathophysiology and the side effects of common therapies, serves as a paradigmatic example, being associated with very high rates of sexual dysfunction in both men and women. Liver transplantation can modify certain hormonal and pathophysiological aspects related to sexual dysfunction, but complete recovery occurs in only a relatively small percentage of patients. This review examines the pathophysiology, epidemiology, and management of sexual and reproductive dysfunction in patients with cirrhosis and those undergoing liver transplantation. It provides a framework for understanding the sources of dysfunction, tools for identifying it in clinical settings, and interventions to improve sexual health and functioning in these patients.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Ivonne Hurtado Díaz de León
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Elliot B. Tapper
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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24
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Bali B, Tuan WJ, Scott A, Bollampally P, Groff D, Leong SL, King VL, Bone C. Assessing men with opioid use disorder for testosterone deficiency after the development of symptoms. J Addict Dis 2025; 43:179-185. [PMID: 38619057 DOI: 10.1080/10550887.2024.2327751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
OBJECTIVE Individuals with opioid use disorder (OUD) have reduced life expectancy and inferior outcomes when treated for depression, diabetes, and fractures. Their elevated risk of testosterone deficiency may contribute to all of these relationships, however few individuals prescribed opioids are evaluated with testosterone assays. The purpose of this study is to determine whether patients with opioid use disorder are evaluated for testosterone deficiency after development of a symptom that may merit investigation, such as erectile dysfunction (ED). METHOD We conducted a retrospective longitudinal cohort study that utilized data from a national database called TriNetX. Patients were eligible for inclusion if they were 20 to 90 years of age, male, and diagnosed with erectile dysfunction. We utilized descriptive statistics and logistic regression to address study aims. RESULTS Testosterone testing was uncommon for all patients with ED. Among 20,658 patients, it was assessed in 11.2% with OUD and 15.1% without OUD. Among those screened, 40% individuals with OUD and ED had testosterone deficiency. Odds of screening those with OUD were lower than matched controls (RR 0.74). CONCLUSIONS Individuals with OUD are at increased risk of testosterone deficiency than the general population, but nearly 90% are not evaluated for this condition even after development symptoms. That 40% of individuals assessed were classified as testosterone deficient suggests endocrine disorders may be contributing to increased fracture risk, chronic pain, and severe depression commonly encountered in patients with OUD. Addressing this care gap may reduce morbidity and mortality associated with opioid use disorder.
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Affiliation(s)
- Bhavna Bali
- Penn State Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Wen Jan Tuan
- Penn State Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Alyssa Scott
- University of Maryland Medical Center, Baltimore, Maryland, USA
| | | | - Destin Groff
- Penn State Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Shou Ling Leong
- Penn State Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Van L King
- University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Curtis Bone
- University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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25
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Kirby M, Naranjo A, Ellis L, Alaka M. Can Testosterone Therapy Be a Viable Option for Men Suffering With the Effects From Hypogonadism due to Prostate Cancer Treatment? Clin Oncol (R Coll Radiol) 2025; 40:103778. [PMID: 39955969 DOI: 10.1016/j.clon.2025.103778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 01/21/2025] [Accepted: 01/23/2025] [Indexed: 02/18/2025]
Affiliation(s)
- M Kirby
- Editor Trends in Urology and Men's Health and President of the British Society for Sexual Medicine (BSSM), Prostate Cancer UK, Fourth Floor, The Counting House, 53 Tooley St, London SE1 2QN, UK.
| | - A Naranjo
- Prostate Cancer UK, Fourth Floor, The Counting House, 53 Tooley St, London SE1 2QN, UK.
| | - L Ellis
- Prostate Cancer UK, Fourth Floor, The Counting House, 53 Tooley St, London SE1 2QN, UK.
| | - M Alaka
- Prostate Cancer UK, Fourth Floor, The Counting House, 53 Tooley St, London SE1 2QN, UK.
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26
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Jiang R, Wang Y. Association between Low Serum Testosterone Levels and All-cause Mortality in Patients With Cardiovascular Disease: A Study Based on the NHANES Database. Cardiovasc Toxicol 2025; 25:604-613. [PMID: 40050519 PMCID: PMC11909012 DOI: 10.1007/s12012-025-09973-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 02/03/2025] [Indexed: 03/15/2025]
Abstract
The association between low serum testosterone levels and all-cause mortality in male and female patients with cardiovascular disease (CVD) was investigated. This study extracted data on CVD patients from the National Health and Nutrition Examination Survey (NHANES) database (1999-2000, 2003-2004, 2011-2012, and 2013-2014). The association between low serum testosterone levels (≤ 300 ng/dL) and all-cause mortality in male and female CVD patients was evaluated using univariate and multivariate Cox regression analyses, with hazard ratios (HR) and 95% confidence intervals (CI). A total of 1,177 participants (689 males) with a mean age of 66.01 ± 12.52 years were included in the study. The median follow-up time was 55 (44, 71) months. Low serum testosterone levels occurred in 487 (70.68%) males and 394 (80.74%) females. Additionally, 202 (29.32%) male patients and 94 (19.26%) female patients with CVD were dead. After adjusting for covariates, low serum testosterone levels were associated with an increased risk of all-cause mortality in male CVD patients (HR = 1.48, 95% CI 1.08-2.02, P = 0.013), while the association was not significant in females. Low serum testosterone levels may be associated with an increased risk of all-cause mortality in male CVD patients, but not in female patients.
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Affiliation(s)
- Rui Jiang
- Department of General Practice, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Yongchen Wang
- Department of General Practice, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
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27
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Zhu D, Pham QM, Wang C, Colonnello E, Yannas D, Nguyen BH, Zhang Y, Jannini EA, Sansone A. Erectile Dysfunction and Oxidative Stress: A Narrative Review. Int J Mol Sci 2025; 26:3073. [PMID: 40243750 PMCID: PMC11988752 DOI: 10.3390/ijms26073073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/18/2025] [Accepted: 03/25/2025] [Indexed: 04/18/2025] Open
Abstract
Erectile dysfunction (ED) is a prevalent condition affecting male sexual health, characterized by the inability to achieve or maintain satisfactory erections. ED has a multifactorial pathogenesis in which psychological, hormonal, neurologic, cardiovascular, and lifestyle factors all contribute to a progressive decline of erectile function. A critical underlying mechanism involves oxidative stress (OS), an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which disrupts endothelial function, reduces nitric oxide (NO) bioavailability, and contributes to vascular dysfunction. This narrative review explores the interplay between OS and ED, focusing on the roles of ROS sources such as NADPH oxidase, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial dysfunction. It examines the impact of OS on chronic conditions like hypertension, diabetes mellitus, hyperlipidemia, hypogonadism, and lifestyle factors like smoking and obesity, which exacerbate ED through endothelial and systemic effects. Emerging research underscores the potential of antioxidant therapies and lifestyle interventions to restore redox balance, improve endothelial function, and mitigate ED's progression. This review also highlights gaps in understanding the molecular pathways linking ROS to ED, emphasizing the need for further research to develop targeted therapeutic strategies.
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Affiliation(s)
- Dake Zhu
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
| | - Quan Minh Pham
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
- Department of Andrology and Sexual Medicine, Hanoi Medical University Hospital, Hanoi 100000, Vietnam
| | - Chunlin Wang
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
- Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Elena Colonnello
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Dimitri Yannas
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
| | - Bac Hoai Nguyen
- Department of Andrology and Sexual Medicine, Hanoi Medical University Hospital, Hanoi 100000, Vietnam
- Surgery Faculty, Hanoi Medical University, Hanoi 100000, Vietnam
| | - Yan Zhang
- Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Emmanuele A. Jannini
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
| | - Andrea Sansone
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; (D.Z.); (Q.M.P.); (E.C.)
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Liu M, Liu Z, Qiao X, Chen C, Guo H, Gu H, Li J, Sun T. An Endogenous Proton-Powered Adaptive Nanomotor for Treating Muscle Atrophy. MATERIALS (BASEL, SWITZERLAND) 2025; 18:1351. [PMID: 40141635 PMCID: PMC11943966 DOI: 10.3390/ma18061351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/06/2025] [Accepted: 03/10/2025] [Indexed: 03/28/2025]
Abstract
Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived FoF1-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded FoF1-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30-40 μm vs. 15-25 μm in untreated). These results highlight the ATM's potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity.
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Affiliation(s)
| | | | | | | | | | - Hao Gu
- College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; (M.L.); (Z.L.); (H.G.)
| | - Junbo Li
- College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; (M.L.); (Z.L.); (H.G.)
| | - Tiedong Sun
- College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; (M.L.); (Z.L.); (H.G.)
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Soejima Y, Otsuka Y, Kawaguchi M, Oguni K, Yamamoto K, Nakano Y, Yasuda M, Tokumasu K, Ueda K, Hasegawa K, Iwata N, Otsuka F. Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis. Int J Mol Sci 2025; 26:2713. [PMID: 40141355 PMCID: PMC11942465 DOI: 10.3390/ijms26062713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/15/2025] [Accepted: 03/16/2025] [Indexed: 03/28/2025] Open
Abstract
Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism.
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Affiliation(s)
- Yoshiaki Soejima
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Yuki Otsuka
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Marina Kawaguchi
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Kohei Oguni
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Koichiro Yamamoto
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Yasuhiro Nakano
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Miho Yasuda
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Kazuki Tokumasu
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Keigo Ueda
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Kosei Hasegawa
- Department of Pediatrics, Okayama University Hospital, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan;
| | - Nahoko Iwata
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
| | - Fumio Otsuka
- Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan; (Y.S.); (Y.O.); (M.K.); (K.O.); (K.Y.); (Y.N.); (M.Y.); (K.T.); (K.U.); (N.I.)
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Liang J, Peng T, Hu J, So KF, Zhang H, Chen G, Zhang YW. Lycium barbarum Glycopeptide Promotes Testosterone Synthesis and Glucose Metabolism in Leydig Cells of the Testis. Biomolecules 2025; 15:425. [PMID: 40149961 PMCID: PMC11940756 DOI: 10.3390/biom15030425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/13/2025] [Accepted: 03/15/2025] [Indexed: 03/29/2025] Open
Abstract
Lycium barbarum extracts have been shown to be effective in male reproductive protection and male infertility. However, its role in enhancing testicular function, such as testosterone synthesis, and the potential mechanism remain to be understood. To elucidate the effects of Lycium barbarum glycopeptide (LbGp) on testosterone synthesis, we isolated primary Leydig cells (LCs) from testes and performed RNA sequencing (RNA seq) on LCs treated with LbGp. In this study, we demonstrated that LbGp promoted testosterone synthesis in LCs both in vivo and in vitro. We also demonstrated that LbGp elevated adenosine 5'-triphosphate (ATP) synthesis and cell proliferation by enhancing glucose metabolism. Mechanistically, LbGp upregulated testosterone synthesis by suppressing TGF-β pathway and enhancing the expression of steroidogenic genes: Cyp11a1, Hsd3b1, Hsd17b3, Star, and Sf-1. These findings indicate that LbGp plays an important role in enhancing testicular function and promoting testosterone synthesis.
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Affiliation(s)
- Jinlian Liang
- School of Life Sciences, Guangzhou University, Guangzhou 510006, China;
| | - Tianchan Peng
- Department of Neurology, Affiliated Hospital of Jinan University, Guangzhou 510632, China; (T.P.); (J.H.)
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China;
| | - Jinrong Hu
- Department of Neurology, Affiliated Hospital of Jinan University, Guangzhou 510632, China; (T.P.); (J.H.)
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China;
| | - Kwok Fai So
- Institute of Clinical Research for Mental Health, The First Affiliated Hospital Jinan University, Guangzhou 510632, China;
- Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou 510515, China
- State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China
| | - Hongyi Zhang
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China;
| | - Guobin Chen
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China;
| | - Yuan-Wei Zhang
- School of Life Sciences, Guangzhou University, Guangzhou 510006, China;
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Kuo YW, Kuo CJ, Le PH, Chang ML, Lin CY, Hsu CM, Lin WP, Chen CW, Lin WR, Ho YP, Su MY, Chiu CT. Risk Factors and Awareness of Bone Fragility in Inflammatory Bowel Disease in Taiwan: A Cross-Sectional Study. Biomedicines 2025; 13:638. [PMID: 40149614 PMCID: PMC11940530 DOI: 10.3390/biomedicines13030638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 02/18/2025] [Accepted: 03/01/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing bone disorders. Awareness and understanding of the disease are crucial for prevention and early diagnosis. Currently, there is no research on the risk factors and knowledge of bone fragility in the population with IBD in Taiwan. This study aimed to evaluate the risk factors and self-assessed knowledge levels of bone health among patients with IBD in Taiwan. Methods: This single-center cross-sectional study included 59 adult patients. Clinical data, blood tests, bone mineral density (BMD), T-score, Z-score, and questionnaires covering self-assessed knowledge, fracture risks, and physical activity were assessed. The patients were divided into normal and low BMD groups. Results: Of all participants, eighteen (30.5%) had low BMD: six (10.2%) had BMD below the expected range, ten (16.9%) had osteopenia, and two (3.4%) had osteoporosis. Vitamin D insufficiency and deficiency were observed in 26.3% and 66.6% of the patients, respectively. According to multivariate analysis, age and sex hormone deficiency are strongly associated with low BMD. Educational interventions significantly improved the patients' self-assessed knowledge levels. Conclusions: Age and sex hormone deficiency are significant factors contributing to low BMD in IBD patients. Not only women but also men with IBD who had symptoms of hypogonadism are at high risk for low BMD. Educational interventions improve self-assessment knowledge regarding the relationship between IBD and bone health.
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Affiliation(s)
- Yao-Wei Kuo
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Microbiota Therapy Center, Taoyuan 333423, Taiwan
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Microbiota Therapy Center, Taoyuan 333423, Taiwan
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Ming-Ling Chang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Cheng-Yu Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Chen-Ming Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Wei-Pin Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Chun-Wei Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
| | - Wey-Ran Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| | - Yu-Pin Ho
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
| | - Ming-Yao Su
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
- Taiwan Association for the Study of Intestinal Disease, Taoyuan 333423, Taiwan
| | - Cheng-Tang Chiu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou 333423, Taiwan; (Y.-W.K.); (P.-H.L.); (M.-L.C.); (C.-Y.L.); (C.-M.H.); (W.-P.L.); (C.-W.C.); (W.-R.L.); (Y.-P.H.); (C.-T.C.)
- College of Medicine, Chang Gung University, Taoyuan 333001, Taiwan;
- Chang Gung Microbiota Therapy Center, Taoyuan 333423, Taiwan
- Chang Gung Inflammatory Bowel Diseases Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Department of Gastroenterology and Hepatology, New Taipei Municipal Tu Cheng Hospital (Built and Operated by Change Gung Medical Foundation), New Taipei City 236017, Taiwan
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Nolan BJ, Cheung AS. Laboratory Monitoring in Transgender and Gender-Diverse Individuals. Clin Chem 2025; 71:358-377. [PMID: 39928416 DOI: 10.1093/clinchem/hvaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 10/30/2024] [Indexed: 02/12/2025]
Abstract
BACKGROUND Increasing numbers of transgender and gender-diverse individuals are seeking initiation of gender-affirming hormone therapy. This aligns an individual's physical characteristics with their gender identity and improves psychological outcomes. Physical changes, including changes to muscle mass and body fat redistribution, can alter sex-specific laboratory reference ranges. CONTENT We review the impact of gender-affirming hormone therapy on laboratory parameters with sex-specific reference ranges, with a focus on hemoglobin/hematocrit, renal function, cardiac biomarkers, and prostate-specific antigen. SUMMARY Gender-affirming hormone therapy results in changes in laboratory parameters with sex-specific reference ranges. For individuals established on gender-affirming hormone therapy, reference ranges that align with an individual's gender identity should be used for hemoglobin/hematocrit, serum creatinine, and high-sensitivity cardiac troponin and N-terminal brain natriuretic peptide. Clinicians should interpret these biomarkers according to the reference range that aligns with one's affirmed gender.
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Affiliation(s)
- Brendan J Nolan
- Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
- Trans Health Research Group, Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia
- Equinox Gender Diverse Clinic, Thorne Harbour Health, Abbotsford, Victoria, Australia
| | - Ada S Cheung
- Trans Health Research Group, Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia
- Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
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Jasuja R, Pencina KM, Lawney B, Stephens-Shields AJ, Ellenberg SS, Snyder PJ, Bhasin S. Modulation of circulating free testosterone fraction by testosterone, dihydrotestosterone, and estradiol during testosterone replacement therapy. Andrology 2025; 13:439-446. [PMID: 39092887 DOI: 10.1111/andr.13707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/26/2024] [Accepted: 07/06/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction. OBJECTIVE To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism. METHODS Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and dihydrotestosterone concentrations over 12 months of testosterone replacement therapy with changes in free testosterone fraction, measured using equilibrium dialysis. We used random forests to evaluate the associations of predicted mean changes in free testosterone fraction with changes in circulating concentrations of each hormone at low, mean, or high change in the other two hormones. RESULTS Testosterone replacement therapy not only increased total testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations, but also the percent free testosterone, even though sex hormone binding globulin levels did not change. The predicted changes in free testosterone fraction during testosterone replacement therapy exhibited a non-linear relationship with changes in each of total testosterone, dihydrotestosterone, and estradiol concentrations. Greater increases in testosterone, dihydrotestosterone, and estradiol levels during testosterone replacement therapy were each associated with higher model-predicted percent free testosterone. Substantially smaller changes in molar concentrations of estradiol and dihydrotestosterone had a greater effect on percent free testosterone than those in testosterone. CONCLUSION During testosterone replacement therapy of men with hypogonadism, changes in testosterone, dihydrotestosterone, and estradiol concentrations each altered percent free testosterone non-linearly. Small changes in estradiol concentrations exerted much larger effect on the free testosterone fraction than testosterone and dihydrotestosterone, suggesting complex interactions of the three hormones with the binding proteins. Assessment of changes in free testosterone during testosterone replacement therapy should include consideration of changes in all three hormones.
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Affiliation(s)
- Ravi Jasuja
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Karol M Pencina
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Brian Lawney
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Alisa J Stephens-Shields
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Susan S Ellenberg
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Peter J Snyder
- Division of Endocrinology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Shalender Bhasin
- Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Babcock MC, DuBose LE, Hildreth KL, Stauffer BL, Kohrt WM, Wenner MM, Moreau KL. Endothelial dysfunction in middle-aged and older men with low testosterone is associated with elevated circulating endothelin-1. Am J Physiol Regul Integr Comp Physiol 2025; 328:R253-R261. [PMID: 39887085 PMCID: PMC12121689 DOI: 10.1152/ajpregu.00218.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/07/2024] [Accepted: 01/26/2025] [Indexed: 02/01/2025]
Abstract
Low testosterone in middle-aged/older men contributes to accelerated vascular aging, including endothelial dysfunction. However, the mechanisms by which low testosterone affects endothelial dysfunction are not well understood. We sought to determine whether higher endothelin-1 (ET-1) levels are associated with reduced brachial artery flow-mediated dilation (FMD) in middle-aged/older men with low testosterone. Plasma ET-1 was quantified in 60 men categorized as young (n = 20, age = 30 ± 4 yr, testosterone = 510 ± 63 ng/dL), middle-aged/older with normal testosterone (n = 20, age = 59 ± 6 yr, testosterone = 512 ± 115 ng/dL), or middle-aged/older with low testosterone (n = 20, age = 60 ± 8 yr, testosterone = 265 ± 47 ng/dL). Endothelial function was determined via brachial artery FMD. Venous and arterial endothelial cells were harvested via endovascular biopsy in a subset of participants and stained for ET-1 expression. Middle-aged/older men with normal testosterone exhibited lower brachial artery FMD (5.7 ± 2.2%) compared with young men (7.3 ± 1.3%, P = 0.020), which was exaggerated in middle-aged/older men with low testosterone (4.0 ± 1.8%, P = 0.010 vs. middle-aged/older men with normal testosterone). Plasma ET-1 was not different between young (5.6 ± 0.9 ng/dL) and middle-aged/older men with normal testosterone (6.0 ± 1.4 ng/dL, P = 0.681) but was higher in middle-aged/older men with low testosterone (7.7 ± 2.8 ng/dL) compared with both groups (P < 0.001 vs. young men; P = 0.013 vs. middle-aged/older men with normal testosterone). There was no difference in venous (P = 0.616) or arterial (P = 0.222) endothelial cell ET-1 expression between groups. There was a significant inverse association between plasma ET-1 and FMD (r =-0.371, P = 0.004). These data suggest that the accelerated age-associated reduction in endothelial dysfunction in middle-aged/older men with low testosterone is related to higher circulating ET-1.NEW & NOTEWORTHY Middle-aged/older men with low testosterone have reduced vascular endothelial function compared with young and age-matched men with normal testosterone. In this manuscript, we demonstrate that men with low testosterone have higher plasma endothelin-1, which is associated with worse brachial artery flow-mediated dilation. The source of higher plasma endothelin-1 remains unknown; however, higher circulating endothelin-1 appears to be a mechanism contributing to reduced vascular endothelial function in men with low testosterone.
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Affiliation(s)
- Matthew C Babcock
- Division of Geriatric Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Lyndsey E DuBose
- Division of Geriatric Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Kerry L Hildreth
- Division of Geriatric Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
| | - Brian L Stauffer
- Division of Cardiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Division of Cardiology, Denver Health Medical Center, Denver, Colorado, United States
| | - Wendy M Kohrt
- Division of Geriatric Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Geriatric Research, Educational and Clinical Center, Veterans Affairs Eastern Colorado, Denver, Colorado, United States
| | - Megan M Wenner
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States
| | - Kerrie L Moreau
- Division of Geriatric Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Geriatric Research, Educational and Clinical Center, Veterans Affairs Eastern Colorado, Denver, Colorado, United States
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Corsini C, Pozzi E, Belladelli F, Bertini A, Negri F, Raffo M, Boeri L, Ventimiglia E, Candela L, D'Arma A, Montorsi F, Salonia A. Age-related decline in total testosterone levels among young men: insights from a large single-center observational study. Int J Impot Res 2025:10.1038/s41443-025-01029-2. [PMID: 39987403 DOI: 10.1038/s41443-025-01029-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 12/13/2024] [Accepted: 02/03/2025] [Indexed: 02/24/2025]
Abstract
We aimed to depict the age-specific distribution of total Testosterone (tT) levels among young men presenting to a single academic centre with uro-andrological complaints. Overall, tT levels from 2593 men aged 20-44 years were analyzed. Men were grouped into 'infertile men' and 'men with sexual dysfunction (SD)' according to their primary complaints. Data was also collected from 71 same-ethnicity age-comparable fertile controls. Linear regression fitted the relationship between tT and increasing age. Distribution of tT was determined for each 5-year age-group, both for the overall population and the subgroups. tT quantiles were reported for each sample sub-group and age-group. Of 2664 men, 1913 (71.81%) were classified as infertile, 680 (25.52%) with SD and 71 as fertile men (2.67%), respectively. tT levels depicted a reduction of 0.14 nmol/L per year between 20 and 44 years of age (p < 0.001) within the overall study population. Significant reduction was also observed for the population stratified by urological complaints (all p < 0.05). This is the first study to describe tT levels as a function of baseline clinical status in a large same-ethnicity cohort of young men, uniformly assessed using a standardized laboratory method.
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Affiliation(s)
- Christian Corsini
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Edoardo Pozzi
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Federico Belladelli
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Alessandro Bertini
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Fausto Negri
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Massimiliano Raffo
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Luca Boeri
- Fondazione IRCCS Ca'Granda Ospedale Maggiore, Milan, Italy
| | - Eugenio Ventimiglia
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Luigi Candela
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alessia D'Arma
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
| | - Francesco Montorsi
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Andrea Salonia
- Division of Experimental Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.
- University Vita-Salute San Raffaele, Milan, Italy.
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Walravens J, Sleumer B, Vos MJ, Snaterse G, Narinx N, Antonio L, Reyns T, Fiers T, Kema IP, Kaufman JM, van de Merbel NC, Lapauw B. SHBG Gene Polymorphisms and Their Influence on Serum SHBG, Total and Free Testosterone Concentrations in Men. J Clin Endocrinol Metab 2025; 110:e641-e649. [PMID: 38652149 DOI: 10.1210/clinem/dgae280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 04/04/2024] [Accepted: 04/19/2024] [Indexed: 04/25/2024]
Abstract
CONTEXT Genetic variation in SHBG structure may affect estimates of sex steroid exposure by altering the affinity of the protein for its ligand. Consequently, free hormone calculations assuming constant binding affinity may, for certain genetic variations, lead to incorrect diagnoses if genetic variation is not taken into consideration. OBJECTIVE To investigate the effects of genetic variation in SHBG on calculated and measured serum free testosterone (T) in men. DESIGN, SETTING AND PARTICIPANTS Population-based sibling-pair study in 999 healthy men aged 25 to 45 (mean, 34.5) years. MAIN OUTCOME MEASURES Genotyping using microarray (Illumina) for single-nucleotide polymorphism (SNPs) suggested to affect binding affinity and/or concentration of SHBG or T. SHBG concentrations were measured using immunoassay and in a subset (n = 32) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total T was measured using LC-MS/MS. Free T was calculated and in a subset (n = 314) measured directly using LC-MS/MS after equilibrium dialysis. RESULTS Allelic frequencies of analyzed SNPs ranged from 0.5% to 58.2%. Compared to wild-type, SHBG concentrations were lower in rs6258 heterozygotes (-24.7%; P < .05) and higher in rs6259 heterozygotes, rs727428 homozygotes, and carriers of rs1799941 (+10.8 to 23.1%; all P < .05). Total T was higher in rs727428 homozygotes and carriers of rs5934505, rs1799941and rs6259 (+3.9 to 21.4%; all P < .05). No clear effects on measured free T were found, except for a trend toward higher values in rs6259 homozygotes, significant for calculated free T (+18.7%; P < .05) in the larger global study population. CONCLUSION In these men, analyzed SNPs were relatively prevalent and affected serum concentrations of total T and SHBG but not calculated or measured free T except for a higher trend in rs6259 homozygotes.
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Affiliation(s)
- Joeri Walravens
- Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium
| | - Bas Sleumer
- ICON Bioanalytical Laboratories, 9407 TK, Assen, The Netherlands
- Department of Analytical Biochemistry, University of Groningen, 9700 AV Groningen, The Netherlands
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
| | - Michel J Vos
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
| | - Gido Snaterse
- Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium
| | - Nick Narinx
- Laboratory of Clinical and Experimental Endocrinology, KU Leuven, 3000 Leuven, Belgium
| | - Leen Antonio
- Laboratory of Clinical and Experimental Endocrinology, KU Leuven, 3000 Leuven, Belgium
| | - Tim Reyns
- Department of Clinical Chemistry, Ghent University Hospital, 9000 Ghent, Belgium
| | - Tom Fiers
- Department of Clinical Chemistry, Ghent University Hospital, 9000 Ghent, Belgium
| | - Ido P Kema
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands
| | - Jean-Marc Kaufman
- Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium
| | - Nico C van de Merbel
- ICON Bioanalytical Laboratories, 9407 TK, Assen, The Netherlands
- Department of Analytical Biochemistry, University of Groningen, 9700 AV Groningen, The Netherlands
| | - Bruno Lapauw
- Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium
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Gonzalez-Gil AM, Barnouin Y, Celli A, Viola V, Villarreal MD, Nava MLD, Sciuk A, Qualls C, Armamento-Villareal R, Villareal DT. Metabolic Effects of Testosterone Added to Intensive Lifestyle Intervention in Older Men With Obesity and Hypogonadism. J Clin Endocrinol Metab 2025; 110:e814-e826. [PMID: 38606934 PMCID: PMC11470114 DOI: 10.1210/clinem/dgae249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 03/26/2024] [Accepted: 04/09/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear. OBJECTIVE To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism. DESIGN Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING Veterans Affairs Medical Center. PARTICIPANTS Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty. INTERVENTIONS LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for 6 months. OUTCOME MEASURES The primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, and adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure; and metabolic syndrome score. RESULTS HbA1c decreased similarly in LT + TRT and LT + Pbo groups (-0.5 ± 0.1 vs -0.6 ± 0.1%, respectively; P = 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in the LT + Pbo group vs 0.2 ± 1.1 mg/dL in the LT + TRT group, P = .01) and adiponectin levels (-408 ± 489 ng/mL in LT + TRT group vs 1832 ± 468 ng/mL in LT + Pbo group, P = .02). CONCLUSION In older men with obesity and hypogonadism, adding TRT for 6 months to LT does not result in further improved cardiometabolic profiles and could potentially blunt some of the metabolic benefits induced by LT.
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Affiliation(s)
- Adrian M. Gonzalez-Gil
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Yoann Barnouin
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Alessandra Celli
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Viola Viola
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Marcos D. Villarreal
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Maria Liza Duremdes Nava
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Adam Sciuk
- Section of Radiology, Michael E DeBakey VA Medical Center, Houston TX, USA
| | - Clifford Qualls
- Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM, USA
| | - Reina Armamento-Villareal
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
| | - Dennis T. Villareal
- Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston TX, USA
- Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine. Houston, TX, USA
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Castro HM, Maritano Furcada J, De Vito EL, Suarez SM, Knoblovits P, Costanzo PR. Association between hypogonadism and severity of chronic obstructive pulmonary disease: A cross-sectional study. Med Clin (Barc) 2025; 164:109-116. [PMID: 39523146 DOI: 10.1016/j.medcli.2024.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION AND OBJECTIVES Chronic obstructive pulmonary disease (COPD) frequently coexists with other comorbidities, including hypogonadism. However, the association between COPD severity and hypogonadism remains controversial. This study aimed to evaluate this association and compare the clinical characteristics of hypogonadal and eugonadal COPD patients. MATERIALS AND METHODS A cross-sectional study including men with stable COPD was performed. Hypogonadism was diagnosed based on the presence of symptoms, according to the Androgen Deficiency in Aging Males questionnaire, and a total testosterone deficit (<300ng/dL). COPD severity was classified according to the Spanish COPD guideline risk classification. A multivariate logistic regression analysis was performed in order to evaluate the relationship between COPD severity and hypogonadism. RESULTS 134 subjects were recruited. The prevalence of hypogonadism was higher in severe COPD than in mild COPD, with a prevalence ratio of 1.8 (p=0.007). An increased odds of hypogonadism was observed in severe COPD subjects (OR 2.60, 95% CI 1.23-5.48, p=0.012) independent of age, body mass index, cardiovascular disease, and chronic renal failure. Hypogonadal COPD patients exhibited lower percentage levels of FVC and FEV1 and a higher degree of dyspnea than compared to eugonadal COPD patients. CONCLUSION Patients with severe COPD had a higher prevalence of hypogonadism compared to those with mild COPD. Additionally, severe COPD was identified as an independent risk factor for hypogonadism. These findings suggest that hypogonadism should be evaluated in patients with COPD, particularly in those with severe disease.
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Affiliation(s)
| | | | - Eduardo Luis De Vito
- Ph.D. Institute of Medical Research Alfredo Lanari, Faculty of Medicine, University of Buenos Aires, Argentina
| | - Sebastian Matias Suarez
- Andrology Section, Endocrinology, Metabolism and Nuclear Medicine Service, Hospital Italiano de Buenos Aires, Argentina
| | - Pablo Knoblovits
- Andrology Section, Endocrinology, Metabolism and Nuclear Medicine Service, Hospital Italiano de Buenos Aires, Argentina
| | - Pablo Rene Costanzo
- Andrology Section, Endocrinology, Metabolism and Nuclear Medicine Service, Hospital Italiano de Buenos Aires, Argentina
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Stumpf MAM, Cercato C, de Melo ME, Mancini MC. Sheer drop ahead: reviewing sarcopenia outcomes in elderly patients undergoing bariatric surgery. Rev Endocr Metab Disord 2025:10.1007/s11154-025-09946-9. [PMID: 39920515 DOI: 10.1007/s11154-025-09946-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/24/2025] [Indexed: 02/09/2025]
Abstract
The global prevalence of obesity among elderly patients continues to rise. Despite the availability of new antiobesity medications, bariatric surgery remains an effective treatment option for carefully selected candidates. However, it is not risk-free, especially in a vulnerable population, predisposing to falls, fractures and sarcopenia. Following bariatric surgery, there is rapid loss of muscle mass, particularly within the first 3 months. Muscle quality, on the other hand, characterized by functionality and indirectly assessed through strength tests, appears to be preserved. This is attributed to reductions in ectopic intramuscular fat deposits. Strategies to mitigate muscle loss and functional impairment include combined exercises (resistive and aerobic training), adequate protein and vitamin D intake, beta-hydroxy-beta-methylbutyrate (HMB) supplementation, and testosterone replacement therapy for men with confirmed hypogonadism. It is important to emphasize that, to date, no specific trial has evaluated the current sarcopenia criteria in elderly patients undergoing bariatric surgery. Therefore, future studies are needed to assess this particularly vulnerable population, not only to monitor changes in muscular health, but also to develop strategies for preventing therapeutic inertia.
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Affiliation(s)
- Matheo Augusto Morandi Stumpf
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil.
| | - Cintia Cercato
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil
| | - Maria E de Melo
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil
| | - Marcio C Mancini
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil
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Zhu L, Hshieh TT, Iyer TK, Morgans AK, Hamnvik OPR. Management of vasomotor symptoms in cancer patients. Oncologist 2025; 30:oyaf002. [PMID: 40037618 PMCID: PMC11879400 DOI: 10.1093/oncolo/oyaf002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 11/11/2024] [Indexed: 03/06/2025] Open
Abstract
Many cancer treatments can lead to reduced levels of sex hormones, which in turn may cause vasomotor symptoms (VMS) such as hot flashes. These symptoms are associated with impaired quality of life, as well as suboptimal tolerability of and adherence to cancer treatment. Hormone therapy, performed by increasing estradiol or testosterone levels, is the gold standard for treatment of VMS. However, this approach is generally contraindicated in patients with hormone-sensitive cancers. Nonhormone agents with low to moderate efficacy in controlling VMS are available, but their use may be limited by side effects and tolerability. In this narrative review, the approach to VMS in cancer patients will be discussed. The evidence for various treatment options, including novel agents such as fezolinetant that target the hypothalamic thermoregulatory pathway, will be evaluated. Finally, special considerations in different patient populations based on cancer types (eg, breast, prostate) and age groups (eg, older adults) will be explored.
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Affiliation(s)
- Ling Zhu
- Department of Endocrinology, Singapore General Hospital, Singapore 169856
- Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
| | - Tammy T Hshieh
- Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
| | - Tara K Iyer
- Menopause and Midlife Clinic, Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02215, United States
| | - Alicia K Morgans
- Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, United States
| | - Ole-Petter R Hamnvik
- Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, United States
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41
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Judge C, Lightowler D, Singh A, Yeap BB, Thin L. Distribution of Serum Testosterone Concentrations in IBD Males and Associations With Inflammatory Bowel Disease Activity. Inflamm Bowel Dis 2025; 31:492-500. [PMID: 39110886 DOI: 10.1093/ibd/izae177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Indexed: 02/11/2025]
Abstract
BACKGROUND An inverse relationship exists between inflammation and testosterone concentrations in non-inflammatory bowel disease (IBD) immune conditions but has not been objectively explored in the IBD male population. We aimed to characterize the distribution of testosterone concentrations in a cohort of males with IBD and identify any relationship between testosterone levels and disease activity. METHODS We conducted a prospective cross-sectional study of male IBD patients. Demographics, disease characteristics, sex-hormone concentration, gonadotropins, C-reactive protein, fecal calprotectin, and patient-reported outcomes on quality of life and erectile function were collected. Relationships between disease activity, biomarkers, patient-reported outcome scores, and testosterone levels were analyzed using univariate and multivariate linear regression analyses. RESULTS A total of 85 male IBD patients were included with a mean age 44 ± 14.1 years, of which 49.4% had Crohn's disease. Mean testosterone concentration was 15.4 ± 5.2 nmol/L and 17.6% had a serum testosterone <10.4 nmol/L. Active disease was associated with lower testosterone concentrations in univariate analysis (β ± SE = -0.25 ± -1.99, P = .02) but not in multivariate analysis (β -0.18 ± 1.75, P = .06). Testosterone concentrations were independently associated with sex hormone-binding globulin levels (β ± SE = 0.45 ± 0.04, P < .0001) and a younger age (β ± SE = -0.32 ± 0.04, P <.0001). Erectile function scores (5-item International Index of Erectile Function) were lower in IBD patients with a longer duration of disease (β ± SE = -0.24 ± 0.006, P = .04). CONCLUSIONS Lower testosterone concentrations in men with IBD may reflect confounding from other factors and are not independently associated with disease activity. Greater awareness and screening for sexual dysfunction should occur in males with IBD, particularly in those with a longer disease duration.
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Affiliation(s)
- Ciaran Judge
- Department of Gastroenterology, Fiona Stanley Hospital, Perth, Western Australia, Australia
| | - Daniel Lightowler
- Department of Gastroenterology, Fiona Stanley Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Western Australia, Australia
| | - Abhey Singh
- Department of Gastroenterology, Fiona Stanley Hospital, Perth, Western Australia, Australia
| | - Bu B Yeap
- Medical School, University of Western Australia, Perth, Western Australia, Australia
- Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia
| | - Lena Thin
- Department of Gastroenterology, Fiona Stanley Hospital, Perth, Western Australia, Australia
- Medical School, University of Western Australia, Perth, Western Australia, Australia
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Fosså SD, Bjerner LJ, Tandstad T, Brydøy M, Dahl AA, Nome RV, Negaard H, Myklebust TÅ, Haugnes HS. Biochemical Hypogonadism in Aging Testicular Cancer Survivors: A Clinical Challenge. EUR UROL SUPPL 2025; 72:10-16. [PMID: 39897186 PMCID: PMC11786855 DOI: 10.1016/j.euros.2024.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2024] [Indexed: 02/04/2025] Open
Abstract
Background and objective Few longitudinal studies have described the prevalence and development of biochemical hypogonadism in aging testicular cancer survivors (TCSs) in comparison to men from the general population (control subjects). Methods Serum total and free testosterone (Ttotal, Tfree) were measured in 593 TCSs median11 and 27 years after TC diagnosis (Survey-First; Survey-Last). Post-treatment adverse health outcomes (AHOs) were recorded. The results were compared to those in 578 control subjects. Treatment was stratified as surgery alone, radiotherapy alone, or platinum-based chemotherapy. Biochemical hypogonadism was defined as Ttotal <8 nmol/l, or as Ttotal <12 nmol/l and Tfree <225 pmol/l. We used multivariable logistic regression analysis to explore associations with age and treatment intensity. Statistical significance was set at p <0.05. Key findings and limitations Between the first and last survey the prevalence of biochemical hypogonadism increased from 12% to 41% in the TSC group and from 5% to 11% in the control group. Three decades after diagnosis, the probability of biochemical hypogonadism was significantly correlated with increasing age and greater treatment intensity. The combined age- and treatment- related probability of hypogonadism was more than threefold higher in the TCS group than in the control group. At the last survey, fewer eugonadal than hypogonadal TCS men reported at least one AHO attributable to androgen deficiency (54% vs 72%; p <0.001). Limitations include the availability of only one blood sample per survey wave. Conclusions and clinical implications For aging TCSs, the probability of biochemical hypogonadism depends on age and prior treatment intensity and is threefold higher than for control subjects at 30 yr after diagnosis. As late hypogonadism is associated with AHO incidence, the development of hypogonadism should be monitored via regular blood tests during TCS follow-up. Patient summary Depending on the treatment they received, older survivors of testicular cancer (TC) are at persistent risk of lower testosterone levels. Our study revealed low testosterone in 40% of TC survivors older than 60 years compared to 10% of similarly aged men from the general population. Low testosterone is associated with chronic conditions such as diabetes, fatigue, and/or erectile dysfunction. Testosterone should be regularly monitored during follow-up for TC survivors.
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Affiliation(s)
- Sophie D. Fosså
- Department of Oncology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Torgrim Tandstad
- Cancer Clinic, St. Olavs University Hospital, Trondheim, Norway
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Marianne Brydøy
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
| | - Alv A. Dahl
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Ragnhild V. Nome
- Department of Medical Biochemistry, Oslo University Hospital, Norway
| | - Helene Negaard
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Tor Å. Myklebust
- Department of Registration, Cancer Registry of Norway, Oslo, Norway
- Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway
| | - Hege S. Haugnes
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
- Institute of Clinical Medicine, Arctic University, Tromsø, Norway
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Lockie AWC, Grice P, Mathur R, Pearce I, Modgil V. Diagnosis and treatment of hypogonadism in men seeking to preserve fertility - what are the options? Int J Impot Res 2025; 37:109-113. [PMID: 38693209 DOI: 10.1038/s41443-024-00897-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 04/05/2024] [Accepted: 04/16/2024] [Indexed: 05/03/2024]
Abstract
Male hypogonadism is a clinical syndrome that results in low testosterone levels and frequently leads to infertility. The syndrome occurs due to disruption at one or more levels of the hypothalamic-pituitary-gonadal axis. Testosterone replacement therapy (TRT) is the most common treatment utilised for male hypogonadism. However, long-acting forms of TRT leads to infertility and so is inappropriate for patients wishing to conceive. For patients who wish to remain fertile, nasal TRT, clomiphene citrate, exogenous gonadotropins, gonadotropin releasing hormone and aromatase inhibitors have been used as alternative treatment options with different degrees of success. A review of the literature was performed to identify the safety and efficacy of alternative treatment options. Gonadotropin releasing hormone can successfully induce spermatogenesis but is impractical to administer. Likewise, aromatase inhibitors have limited use due to inducing osteopenia. Nasal TRT may be a good treatment option for these patients, but its efficacy has so far only been demonstrated in small sample sizes. However, clomiphene citrate and exogenous gonadotropins are safe, offer good symptom control and can successfully induce fertility in hypogonadism patients.
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Affiliation(s)
| | - Peter Grice
- Northampton General Hospital, Northampton, UK
| | - Raj Mathur
- Manchester Royal Infirmary, Manchester, UK
| | - Ian Pearce
- Manchester Royal Infirmary, Manchester, UK
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Fendereski K, Horns JJ, Dehghanbanadaki H, Watkins CM, Hotaling JM. The Impact of Testosterone Therapy on Benign Prostatic Hyperplasia in Hypogonadal Males. Urology 2025; 196:325-332. [PMID: 39550043 DOI: 10.1016/j.urology.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 10/03/2024] [Accepted: 11/05/2024] [Indexed: 11/18/2024]
Abstract
OBJECTIVE To determine the impact of testosterone therapy (TT) on the incidence of benign prostatic hyperplasia (BPH) in a large cohort of hypogonadal males and to evaluate the relationship between TT in hypogonadal males and prostatic interventions. METHODS We used the 2011-2020 International Business Machines Corporation MarketScan database to identify hypogonadal males above 18 years old and determine if they received TT. International Classification of Diseases, 9th and 10th Revisions, Current Procedural Terminology, Healthcare Common Procedure Coding System Procedure Codes, and National Drug Code (NDC) codes were used for diagnoses, interventions, and medications. We ran Cox proportional hazard models to determine the effect of TT on receiving a diagnosis of BPH and interventions. Models were adjusted for age, region, population density, and comorbidities, with TT within the last 6 months considered a time-varying covariate. RESULTS In our total cohort of 882,570 hypogonadal males, 157,185 (17.8%) were diagnosed with BPH. For the first 2.5 years after hypogonadism diagnosis, there was no significant difference in the diagnosis of prostatic hyperplasia between patients on TT and those who were not (HR:1, 95%CI:0.98-1.01, P = .66). However, from 2.5 years onward, males who were on TT had a 32% higher risk of receiving a diagnosis of BPH (HR:1.32, 95%CI:1.28-1.36, P <.001). Hypogonadal males with BPH who received TT showed no significant difference in interventions compared to those who did not receive testosterone (HR:0.95, 95%CI:0.89-1, P = .08). CONCLUSION In the long term, TT increased the risk of receiving a diagnosis of BPH in hypogonadal males. TT in hypogonadal males with BPH did not change the need for interventions.
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Affiliation(s)
- Kiarad Fendereski
- Division of Urology, Department of Surgery, University of Utah Health, Salt Lake City, UT.
| | - Joshua John Horns
- Division of Urology, Department of Surgery, University of Utah Health, Salt Lake City, UT.
| | - Hojat Dehghanbanadaki
- Division of Urology, Department of Surgery, University of Utah Health, Salt Lake City, UT.
| | | | - James M Hotaling
- Division of Urology, Department of Surgery, University of Utah Health, Salt Lake City, UT.
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Raheem OA, Barham A. Editorial Comment on "Castration Levels of Testosterone Results in Atrophy of Androgen-sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism". Urology 2025; 196:321-322. [PMID: 39550044 DOI: 10.1016/j.urology.2024.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 11/05/2024] [Indexed: 11/18/2024]
Affiliation(s)
- Omer A Raheem
- Urology Department, Surgical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
| | - Alaeddin Barham
- Urology Department, Surgical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
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Rathi N, Blake Z, Hyman J, Nemirovsky DR, Gelikman DG, Hesswani C, Koller C, Nethala D, Mendhiratta N, Kenigsberg AP, Noun J, Dahut W, Karzai FY, Linehan WM, Pinto PA, Turkbey B, Gurram S. Castration Levels of Testosterone Results in Atrophy of Androgen-sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism. Urology 2025; 196:313-320. [PMID: 39427924 PMCID: PMC11807738 DOI: 10.1016/j.urology.2024.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/13/2024] [Accepted: 10/02/2024] [Indexed: 10/22/2024]
Abstract
OBJECTIVE To evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship. METHODS Data were prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width. RESULTS Thirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dL, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (P <.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (P = .032). CONCLUSION Androgen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.
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Affiliation(s)
- Nityam Rathi
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | - Zoë Blake
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | - Jason Hyman
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | | | - David G Gelikman
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD; Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Charles Hesswani
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | | | - Daniel Nethala
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | - Neil Mendhiratta
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | | | - Jibriel Noun
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | - William Dahut
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD; Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Fatima Y Karzai
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD; Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | | | - Peter A Pinto
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD
| | - Baris Turkbey
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD; Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Sandeep Gurram
- Urologic Oncology Branch National Cancer Institute, Bethesda, MD.
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M. S, M. O, P. F, M. P. Arrested Puberty in a Young Adult With a Macroprolactinoma: Case Report and Literature Review. Case Rep Endocrinol 2025; 2025:5388529. [PMID: 39949381 PMCID: PMC11824852 DOI: 10.1155/crie/5388529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 12/11/2024] [Indexed: 02/16/2025] Open
Abstract
Prolactinoma is the most common pituitary tumor, with clinical presentations varying according to sex, age of onset, tumor size, and prolactin (PRL) levels. These tumors are rare in the pediatric and adolescent populations. Hyperprolactinemia leads to hypogonadotropic hypogonadism, resulting in reproductive, metabolic, sexual, and skeletal consequences that can affect puberty development. Here, we present the case of a 23-year-old male patient diagnosed with arrested puberty secondary to a macroprolactinoma. The clinical presentation, diagnostic approach, therapeutic management, and a literature review are discussed.
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Affiliation(s)
- Sánchez M.
- Unidad Académica de Endocrinología y Metabolismo, Hospital de Clínicas, Facultad de Medicina, UdelaR, Montevideo, Uruguay
| | - Otazú M.
- Unidad Académica de Endocrinología y Metabolismo, Hospital de Clínicas, Facultad de Medicina, UdelaR, Montevideo, Uruguay
| | - Furtenbach P.
- Unidad Académica de Endocrinología y Metabolismo, Hospital de Clínicas, Facultad de Medicina, UdelaR, Montevideo, Uruguay
| | - Piñeyro M.
- Unidad Académica de Endocrinología y Metabolismo, Hospital de Clínicas, Facultad de Medicina, UdelaR, Montevideo, Uruguay
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Goldstein I, Chidambaram N, Dobs A, King S, Miner M, Ramasamy R, Yafi FA, Khera M. Newer formulations of oral testosterone undecanoate: development and liver side effects. Sex Med Rev 2025; 13:33-40. [PMID: 39291780 DOI: 10.1093/sxmrev/qeae062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 06/27/2024] [Indexed: 09/19/2024]
Abstract
INTRODUCTION Testosterone deficiency is a clinical disorder due to either failure of the testes to produce testosterone or failure of the hypothalamus or pituitary to produce sufficient gonadotropins. Previous formulations of oral testosterone therapy, particularly methyltestosterone, have been associated with adverse liver effects. Many different routes of testosterone delivery have been developed, each with their own administrative benefits and challenges. Newer formulations of oral testosterone undecanoate (TU) provide a convenient administration option, although their use has been limited by hepatotoxicity concerns based on older methyltestosterone data, and prescribing physicians may still be concerned about adverse liver effects. OBJECTIVES In this review, we discuss the history of oral testosterone development, clarify the mechanism of action of oral TU, and describe the relevant liver safety findings. METHODS Relevant literature was allocated to present a review on the history of oral TU development and the mechanism of action of oral TU. We pooled data from individual studies of oral TU products to present a safety summary. RESULTS Overall, safety results from studies of the newer formulations of oral TU showed that increased liver function test values are not generally associated with oral TU formulations and that no clinically significant liver toxicities were noted in clinical trials of oral TU. CONCLUSION Continued research into the safety of oral TU will contribute to a better understanding of the potential risks in patients receiving this therapy, an outcome that highlights the importance of providing patient education and reassurance regarding oral TU safety.
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Affiliation(s)
- Irwin Goldstein
- University of California at San Diego, San Diego, CA 92120, United States
| | | | - Adrian Dobs
- The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
| | - Shelby King
- Halozyme, San Diego, CA 92130, United States
| | - Martin Miner
- Men's Health Center, Miriam Hospital, Providence, RI 02906, United States
| | - Ranjith Ramasamy
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL 33136, United States
- Jumeirah American Clinic, Dubai, UAE
| | | | - Mohit Khera
- Department of Urology, University of California Irvine, Irvine, CA 92660, United States
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Papadakis GE, Favre L, Zouaghi Y, Vionnet N, Niederländer NJ, Adamo M, Acierno JS, Berdous D, Boizot A, Meylan J, Ivanisevic J, Paccou E, Gallart-Ayala H, Reyns T, Van Caeneghem E, Lapauw B, Pasquier J, Aleman Y, Mantziari S, Salamin O, Nicoli R, Kuuranne T, Fiers T, Hagmann P, Santoni F, Messina A, Pitteloud N. Multiomics unravels the complexity of male obesity: a prospective observational study. J Transl Med 2025; 23:138. [PMID: 39885510 PMCID: PMC11783726 DOI: 10.1186/s12967-024-06040-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/25/2024] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Obesity is associated with varying degrees of metabolic dysfunction. In this study, we aimed to discover markers of the severity of metabolic impairment in men with obesity via a multiomics approach. METHODS Thirty-two morbidly men with obesity who were candidates for Roux-en-Y gastric bypass (RYGB) surgery were prospectively followed. Nine healthy adults served as controls. Deep phenotyping, including targeted metabolomics, transcriptomics, and brain magnetic resonance imaging (MRI), was performed. RESULTS Testosterone emerged as a key contributor to phenotypic variability via principal component analysis and was therefore used to further categorize obese patients as having or not having hypogonadotropic hypogonadism (HH). Despite having comparable body mass indices, obese individuals with HH presented with worse metabolic defects than obese individuals without HH, including higher insulin resistance, as well as MRI signs of hypothalamic inflammation and a specific blood transcriptomics signature. The upregulated genes were involved mainly in inflammation, mitochondrial function, and protein translation. Integration of gene expression and clinical data revealed high FGF21 and low cortisol levels as the top markers correlated with the transcriptomic signature of metabolic risk. Following RYGB-induced substantial weight loss, testosterone levels markedly increased in both obese individuals with and without HH, challenging the current definition of hypogonadism. A longitudinal study in a subset of men with obesity following bariatric surgery revealed a unique FGF21 trajectory with a sharp peak at one month post-RYGB that correlated with metabolic and reproductive improvements. CONCLUSIONS Combining clinical, biochemical, and molecular markers allows adequate stratification of metabolic risk in men with obesity and provides novel tools for personalized care.
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Affiliation(s)
- Georgios E Papadakis
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Lucie Favre
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Yassine Zouaghi
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Nathalie Vionnet
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
| | - Nicolas J Niederländer
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Michela Adamo
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - James S Acierno
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Dassine Berdous
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Alexia Boizot
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
| | - Jenny Meylan
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
| | - Julijana Ivanisevic
- Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 19, CH-1005, Lausanne, Switzerland
| | - Emmanuelle Paccou
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
| | - Hector Gallart-Ayala
- Metabolomics Platform, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 19, CH-1005, Lausanne, Switzerland
| | - Tim Reyns
- Department of Clinical Chemistry, Ghent University Hospital, 9000, Ghent, Belgium
| | - Elise Van Caeneghem
- Department of Clinical Chemistry, Ghent University Hospital, 9000, Ghent, Belgium
| | - Bruno Lapauw
- Department of Clinical Chemistry, Ghent University Hospital, 9000, Ghent, Belgium
| | - Jérôme Pasquier
- Center for Primary Care and Public Health, University of Lausanne, CH-1011, Lausanne, Switzerland
| | - Yasser Aleman
- Division of Radio-Diagnostics and Interventional Radiology, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Styliani Mantziari
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
- Department of Visceral Surgery, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Olivier Salamin
- Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Lausanne University Hospital and University of Geneva, Chemin de La Vulliette 4, CH-1000, Lausanne, Switzerland
| | - Raul Nicoli
- Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Lausanne University Hospital and University of Geneva, Chemin de La Vulliette 4, CH-1000, Lausanne, Switzerland
| | - Tiia Kuuranne
- Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, Lausanne University Hospital and University of Geneva, Chemin de La Vulliette 4, CH-1000, Lausanne, Switzerland
| | - Tom Fiers
- Department of Clinical Chemistry, Ghent University Hospital, 9000, Ghent, Belgium
| | - Patric Hagmann
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
- Division of Radio-Diagnostics and Interventional Radiology, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland
| | - Federico Santoni
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Andrea Messina
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland
| | - Nelly Pitteloud
- Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Avenue de la Sallaz 8, CH-1011, Lausanne, Switzerland.
- Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 21, CH-1005, Lausanne, Switzerland.
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Amano T. Late-onset hypogonadism: current methods of clinical diagnosis and treatment in Japan. Asian J Androl 2025:00129336-990000000-00280. [PMID: 39887188 DOI: 10.4103/aja2024111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 11/26/2024] [Indexed: 02/01/2025] Open
Abstract
ABSTRACT Testosterone affects several organs in the body and is very important for male well-being. Aging men with late-onset hypogonadism (LOH) experience physiologic, psychiatric, and sexual symptoms related to a decline in the serum concentration of testosterone with age. However, it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms. Therefore, it is difficult to diagnose and treat patients with LOH. In addition, the symptoms, response to testosterone replacement therapy (TRT), and medical insurance coverage differ among ethnicities and countries. The evaluation of testosterone is essential for the diagnosis and treatment of LOH. The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity. A low number of glutamine repeats is indicative of high androgenic activity, and the number shows ethnicity-related differences (fewer in African American than in Caucasian people and more in East Asian people). The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration. The Aging Male Symptoms scale is widely used to evaluate the symptoms. The normal range of total testosterone concentration varies around the world; therefore, clinicians should follow the guidelines of their regional academic society. The principal treatment for LOH is TRT. There are many types of TRT and other treatment strategies are also available. Thus, physicians should treat LOH according to each patient's situation, considering related disorders, such as diabetes, osteoporosis, metabolic syndrome, and depression.
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Affiliation(s)
- Toshiyasu Amano
- Department of Urology, Nagano Red Cross Hospital, Nagano 380-8528, Japan
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