The Aging Male[JOURNAL]
Sun
200 papers
The association between age and mortality in men with adult-onset testosterone deficiency is altered by testosterone therapy.
Mann A, Strange RC, König CS … +9 more , Hackett G, Haider A, Haider KS, Desnerck P, Zitzmann M, Saad F, Dhebar MM, Marriott J, Ramachandran S
Aging Male · 2026 Dec · PMID 42391314 · Publisher ↗
BACKGROUND: Using the Gompertz-Makeham model, we describe associations between age and the probability of mortality in men with adult-onset testosterone deficiency (TD), stratified by testosterone undecanoate (TU) treatm...
BACKGROUND: Using the Gompertz-Makeham model, we describe associations between age and the probability of mortality in men with adult-onset testosterone deficiency (TD), stratified by testosterone undecanoate (TU) treatment and type 2 diabetes (T2DM). METHODS: We analyzed a registry of 737 men (353 and 384 men on/not on TU, respectively) with adult-onset TD with nearly 9 years of follow-up. We compared associations between age and mortality using nonparametric and logistic regression models (estimating individual mortality probability) in men stratified by TU treatment and T2DM. RESULTS: Mortality was lower ( < 0.001) in men on TU compared to men opting against TU. In the men on TU, age was associated with mortality (odds ratio (OR): 1.26, 95% confidence interval (CI): 1.13-1.40) in the nonlinear pattern expected in the Gompertz‒Makeham model. However, age was not associated with mortality in men not on TU (OR: 1.03, 95% CI: 0.98-1.08). T2DM status did not affect these associations. CONCLUSION: The association between age and mortality differed between men on TU and those opting against treatment. In untreated men, features of metabolic syndrome worsened, which perhaps minimized the relationship between age and mortality. In men on TU, these metabolic risk factors improved, perhaps restoring the association between age and mortality.
Associations of metabolic heterogeneity of obesity with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): longitudinal cohort and cross-sectional study.
Xiao Q, Xiao W
Aging Male · 2026 Dec · PMID 42359581 · Publisher ↗
BACKGROUND: Based on data from the China Health and Retirement Longitudinal Study (CHARLS) and a Hunan cross-sectional study, the study investigated the link between metabolic heterogeneity of obesity (MHO) and lower uri...
BACKGROUND: Based on data from the China Health and Retirement Longitudinal Study (CHARLS) and a Hunan cross-sectional study, the study investigated the link between metabolic heterogeneity of obesity (MHO) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). METHODS: The cohort study included 2278 males, and the cross-sectional study included 851 males; all were divided into four BMI-metabolic categories: MHNW, MUNW, MHOO, and MUOO. RESULTS: This cross-sectional study found LUTS/BPH patients were younger, more urban-dwelling, with higher education and MHOO/MUOO prevalence. Both studies showed age, residence, education, obesity, and metabolic heterogeneity were linked with LUTS/BPH; CHARLS also linked arthritis and liver illness to LUTS/BPH. CONCLUSIONS: Logistic regression showed unadjusted associations for MHOO (OR = 1.84, 95% CI: 1.22-2.78, = 0.0038) and MUOO (OR = 1.59, 95% CI: 1.15-2.19, = 0.0051), but only MHOO remained significant after adjusting for age and multiple factors, indicating that it was independently associated with LUTS/BPH regardless of confounders.
Ubiquitination-anchored signature defines neuroendocrine prostate cancer: hub genes and single-cell ecosystem insights from integrated bioinformatics analysis of public transcriptomic datasets.
Zhao Z, Qiu L, Li Z … +8 more , Wu J, Ni Q, Li S, Wang H, Shi C, Lin X, Liu Y, Lu J
Aging Male · 2026 Dec · PMID 42249833 · Publisher ↗
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive, treatment-refractory state that often emerges under androgen-receptor pathway inhibition. We hypothesized that dysregulated ubiquitination underpins NEP...
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive, treatment-refractory state that often emerges under androgen-receptor pathway inhibition. We hypothesized that dysregulated ubiquitination underpins NEPC lineage plasticity and that integrating bulk and single-cell transcriptomes would define a ubiquitination-centered signature and tumor microenvironment (TME) circuits of diagnostic and therapeutic relevance. METHODS: Public bulk transcriptomic datasets were combined to compare NEPC with prostate adenocarcinoma, including a GEO discovery cohort of 49 tissue samples from GSE32967 and GSE104786, and intersected with a curated ubiquitination-related gene universe to derive ubiquitination-related differentially expressed genes (URDEGs). Co-expression networks, functional enrichment, and protein-protein interaction (PPI) network topology analyses were used to identify and prioritize candidate hub genes. An independent scRNA-seq cohort was integrated for biological contextualization to map cellular lineages, hub gene localization, and intercellular communication. RESULTS: We identified 317 URDEGs that clearly segregated NEPC from conventional prostate cancer and clustered into NEPC-associated modules enriched for cell-cycle and mitotic programs. Network integration yielded an 11-gene hub panel, including AURKA, CCNA2, EZH2, FGFR1, and TTK. In the single-cell dataset, 25,325 cells were retained after quality control, and UMAP resolved 17 clusters annotated into 8 major lineages. Single-cell mapping further revealed lineage-biased hub gene expression and highlighted a prominent stromal-vascular as well as immune MIF-CD74/CXCR4 signaling axis. CONCLUSIONS: This integrative analysis identifies a ubiquitination‑anchored transcriptomic signature and associated hub‑gene network that are consistently associated with NEPC in public bulk datasets and supported by cell‑type-resolved patterns in an independent scRNA‑seq cohort; these findings nominate candidate biomarkers and therapeutic hypotheses that warrant external validation in prospectively collected, clinically annotated cohorts with protein‑level assessment.
SPISE index and ensemble machine learning refine cardiovascular risk stratification in stage 0-3 CKM syndrome.
Wang L, Wang H, Liu T … +2 more , Zhang N, Zhao L
Aging Male · 2026 Dec · PMID 42101474 · Publisher ↗
BACKGROUND: While the single-point insulin sensitivity estimator (SPISE) shows promise as an insulin resistance biomarker, its association with cardiovascular disease (CVD) in early CKM stages (0-3) remains underexplored...
BACKGROUND: While the single-point insulin sensitivity estimator (SPISE) shows promise as an insulin resistance biomarker, its association with cardiovascular disease (CVD) in early CKM stages (0-3) remains underexplored. METHODS: We analyzed 6480 participants with CKM stage 0-3 from the China Health and Retirement Longitudinal Study. CVD outcomes were assessed relative to SPISE index levels. An ensemble machine learning model was employed to predict CVD risk. RESULTS: 6480 subjects were enrolled, of whom 967 developed CVD. After stratifying participants into SPISE quartiles (Q1-Q4) and adjusting for covariates, higher quartiles were linked to a lower CVD risk. This study developed an LR+GMM (Logistic Regression + Gaussian Mixture Model) ensemble model to predict CVD risk using five strong predictors: SPISE, high-density lipoprotein cholesterol (HDL-c), diastolic blood pressure (DBP), body mass index (BMI), and glycated hemoglobin (HbA1c). The model performed well, achieving an accuracy (ACC) of 0.986 and an area under the receiver operating characteristic curve (AUC) of 0.932. CONCLUSIONS: The SPISE index is a significant inverse predictor of CVD risk in individuals with stage 0-3 CKM syndrome. The LR+GMM ensemble model, incorporating the SPISE index and four clinical metrics, demonstrated outstanding predictive performance.
Relationship between Chinese visceral adiposity index and bone mineral density in patients with type 2 diabetes mellitus.
Ruan Y, Shi L
Aging Male · 2026 Dec · PMID 42024037 · Publisher ↗
BACKGROUND: The relationship between visceral adiposity and bone mineral density (BMD) in type 2 diabetes (T2DM) remains inconsistent, potentially influenced by glycemic control. The Chinese Visceral Adiposity Index (CVA...
BACKGROUND: The relationship between visceral adiposity and bone mineral density (BMD) in type 2 diabetes (T2DM) remains inconsistent, potentially influenced by glycemic control. The Chinese Visceral Adiposity Index (CVAI) is a validated surrogate marker for visceral fat, but its association with BMD in T2DM is unexplored. METHODS: This cross-sectional study of 202 T2DM patients (aged ≥40 years) assessed BMD via DXA. CVAI was calculated from age, BMI, waist circumference, triglycerides, and HDL-C. Participants were stratified by glycemic control (HbA1c < 9% vs. ≥9%). Associations were analyzed using correlation and multivariate linear regression. RESULTS: Higher CVAI correlated with increased BMD at the lumbar spine ( = 0.184) and total hip ( = 0.269). This positive association was significant only in patients with HbA1c < 9% (total hip: = 0.310) but absent in those with HbA1c ≥9%. CVAI remained an independent positive predictor of total hip BMD (β = 0.358, < 0.001) after adjusting for age and sex. CONCLUSION: A moderate level of visceral adiposity, indicated by CVAI, may be associated with higher BMD in T2DM patients with better glycemic control. Optimal glucose management appears critical for preserving this potential skeletal benefit.
Testosterone deficiency in aging males: a dual threat to vascular and bone health through coronary artery calcification and osteoporosis - a narrative review.
Li S
Aging Male · 2026 Dec · PMID 42012850 · Publisher ↗
Testosterone deficiency, a common condition in aging males, has been increasingly associated with two significant age-related conditions: coronary artery calcification (CAC) and osteoporosis. This comprehensive review ex...
Testosterone deficiency, a common condition in aging males, has been increasingly associated with two significant age-related conditions: coronary artery calcification (CAC) and osteoporosis. This comprehensive review examines the current evidence regarding the complex relationship between testosterone levels and these conditions in elderly male patients. We synthesize findings from recent studies exploring the pathophysiological mechanisms, clinical correlations, and potential therapeutic implications of testosterone status in cardiovascular and bone health. Evidence suggests that low testosterone levels are associated with increased coronary calcification burden, more advanced atherosclerotic plaques, and greater risk of osteoporotic fractures. The biological mechanisms connecting testosterone deficiency to these conditions include impaired lipid metabolism, chronic inflammation, endothelial dysfunction, disrupted bone remodeling processes, and altered calcium homeostasis. While observational studies consistently demonstrate associations between hypogonadism and worse cardiovascular and bone outcomes, results from interventional trials on testosterone replacement therapy (TRT) remain mixed, with some studies showing potential benefits for bone health but uncertain effects on cardiovascular risk. This review highlights the need for further research to establish causality, elucidate underlying mechanisms, and develop targeted therapeutic strategies for elderly men with testosterone deficiency affecting cardiovascular and skeletal systems.
The effect of dutasteride on storage symptoms in men with lower urinary tract symptoms: a REDUCE trial analysis.
Hernandez-Tirado A, Zheng R, Dadashian E … +3 more , Nik-Ahd F, Moreira D, Freedland SJ
Aging Male · 2026 Dec · PMID 42011680 · Publisher ↗
BACKGROUND: Dutasteride is used to treat voiding symptoms; its impact on storage symptoms is unclear. METHODS: We reviewed 8122 men in the placebo and dutasteride arms from the REDUCE trial. Lower urinary tract symptoms...
BACKGROUND: Dutasteride is used to treat voiding symptoms; its impact on storage symptoms is unclear. METHODS: We reviewed 8122 men in the placebo and dutasteride arms from the REDUCE trial. Lower urinary tract symptoms outcomes were measured with international prostate symptom score and subscores. RESULTS: At 2-year follow-up, dutasteride significantly reduced the total International Prostate Symptom Score and voiding subscore versus placebo (both < 0.001), but not storage symptoms (= 0.09) or nocturia (= 0.2). By 4 years, improvements in the total score and voiding subscores remained, but now extended to storage symptoms (< 0.001) and nocturia (= 0.003), though the impact on storage symptoms was modest (0.62 points improvement). CONCLUSION: While dutasteride reduces storage symptoms, it takes several years, and the overall effect is modest and unlikely to be clinically meaningful. Timely, comprehensive lower urinary tract symptoms management may require additional therapy.
Testosterone replacement therapy in older men: skeletal outcomes and fracture risk.
Szarpak L, Al-Jeabory M, Pecold J … +1 more , Maslyk M
Aging Male · 2026 Dec · PMID 41947034 · Publisher ↗
INTRODUCTION: Testosterone replacement therapy (TRT) is increasingly prescribed to older men with symptomatic testosterone deficiency, yet the balance of musculoskeletal benefits and harms remains uncertain. OBJECTIVES:...
INTRODUCTION: Testosterone replacement therapy (TRT) is increasingly prescribed to older men with symptomatic testosterone deficiency, yet the balance of musculoskeletal benefits and harms remains uncertain. OBJECTIVES: To synthesise current evidence on TRT-related effects on bone, muscle, falls/fractures, and tendon outcomes in older men, and to contextualise these findings within plausible mechanisms and recent regulatory positions. METHODS: We conducted a state-of-the-art narrative review of randomised controlled trials, meta-analyses, clinical guidelines, and large observational/registry-based studies assessing musculoskeletal and tendon endpoints in older men receiving TRT. RESULTS: Across trials, TRT consistently increases lean mass and reduces fat mass, while improvements in strength and physical performance are generally modest and heterogeneous. Evidence indicates small-to-moderate increases in bone mineral density, particularly at the spine and hip, but robust proof of fracture prevention is lacking. In the Testosterone Trials, TRT improved several surrogate musculoskeletal measures but did not reduce falls. In the TRAVERSE fracture analysis, TRT did not lower fracture risk and a higher fracture incidence was reported in the TRT group (hazard ratio 1.43). DISCUSSION: Observational data suggest an association between TRT initiation and tendon injury, although causal inference is limited by confounding and detection bias. A potential explanation is a temporal mismatch between relatively rapid gains in muscle capacity and slower adaptation of tendon and bone to increased loading. CONCLUSION: In older men with confirmed hypogonadism, TRT may improve body composition and selected functional outcomes, but it should not be considered a disease-modifying strategy for preventing falls or fractures. Careful patient selection, assessment of baseline fracture/tendon risk, and structured monitoring are warranted, particularly in the context of evolving regulatory warnings regarding TRT use for age-related low testosterone.
Narrative-based sexual medicine. A collection of patients' stories and clinical cases to better understand the management of erectile dysfunction with type 5 phosphodiesterase inhibitors in the real life.
Sansone A, Mantegazza R, Vignesh SO … +1 more , A Jannini E
Aging Male · 2026 Dec · PMID 41928386 · Publisher ↗
INTRODUCTION: Narrative-based medicine (NBM) integrates patient stories with the clinician's perspective and scientific evidence to personalize care. This approach is particularly well suited to sexual medicine. Sexual d...
INTRODUCTION: Narrative-based medicine (NBM) integrates patient stories with the clinician's perspective and scientific evidence to personalize care. This approach is particularly well suited to sexual medicine. Sexual dysfunctions - especially erectile dysfunction (ED) - are highly multifaceted conditions in which individual histories and couple dynamics substantially influence diagnosis and treatment. Traditional evidence-based tools may fail to capture this complexity, as sexual symptoms emerge from the interplay of several connected systems. . FINDINGS: This narrative review presents a series of realistic clinical vignettes illustrating the challenges of ED management within contemporary Italian sexual medicine, using the multidisciplinary Italian Society of Andrology and Sexual Medicine (SIAMS) guidelines as a normative framework. Each vignette is accompanied by scientific commentary grounded on evidence provided by the SIAMS guidelines. ED is framed as a sentinel symptom of systemic health, as postulated by the Systems Sexology which offer integrative models connecting the prescription of virtuous lifestyles with the type 5 phosphodiesterase inhibitors (PDE5i). CONCLUSION: This perspective underscores the inadequacy of simplistic "symptom-pill" approaches and highlights the need for personalized, multidimensional care, including alternative pharmaceutical formulations of PDE5i, such as the orodispersible film, that may enhance discretion, acceptability, and adherence.
Association between circadian syndrome and frailty in middle-aged and elderly people: a longitudinal study.
Peng Y, Dai N, Zhao D
Aging Male · 2026 Dec · PMID 41928385 · Publisher ↗
BACKGROUND: This study aimed to investigate the cross-sectional and longitudinal associations between Circadian syndrome (CircS) and frailty using nationally representative data from CHARLS (China Longitudinal Study of H...
BACKGROUND: This study aimed to investigate the cross-sectional and longitudinal associations between Circadian syndrome (CircS) and frailty using nationally representative data from CHARLS (China Longitudinal Study of Health and Retirement). METHODS: The cross-sectional study enrolled 9584 Chinese adults aged 45 years and older in 2011. Logistic regression models were used to investigate the associations of CircS with frailty status and frailty index. The longitudinal study enrolled 6363 eligible participants. Cox regression models were used for longitudinal association analysis and subgroup analyses. RESULTS: Cross-sectional analysis showed that CircS was positively correlated with the frailty index ( = 0.041, 95% CI: 0.036-0.045, < 0.001) and frailty status (OR = 2.008, 95% CI: 1.770-2.279, < 0.001). During the 7-year follow-up, a total of 1,833 participants (28.81%) developed frailty. CircS was significantly associated with the risk of developing frailty status (HR = 1.499, 95% CI: 1.367-1.644, < 0.001). CONCLUSION: This study provides the first longitudinal evidence that CircS is a significant predictor of frailty among older adults. These findings underscore the importance of circadian health in the aging process and suggest that targeting CircS through lifestyle and behavioral interventions may represent a promising strategy for frailty prevention and management.
Exploring the causal links among immune cell characteristics and prostatitis: a bidirectional two-sample Mendelian randomization study.
Wang Y, Xue C, Xu Z … +2 more , Zhu B, Xing Q
Aging Male · 2026 Dec · PMID 41906748 · Publisher ↗
PURPOSE: We aimed to conduct a bidirectional two-sample Mendelian randomization (MR) analysis to comprehensively explore the causal associations between prostatitis and 731 immune cell properties. METHODS: A bidirectiona...
PURPOSE: We aimed to conduct a bidirectional two-sample Mendelian randomization (MR) analysis to comprehensively explore the causal associations between prostatitis and 731 immune cell properties. METHODS: A bidirectional two-sample MR analysis was conducted to reveal their causal correlations. Sensitivity analyses were performed to assess the robustness of the results. RESULTS: A total of 12 immune cells were found to be significantly linked with prostatitis risks, including CD39+ secreting Treg AC, B cell AC, NK %CD3- lymphocyte, CD28+ CD45RA- CD8dim %T cell, CD3 on CM CD4+ , CD3 on CD45RA- CD4+ , CD3 on CD39+ secreting Treg, CD3 on CD28+ CD4+ , CD3 on CD28+ CD45RA- CD8br, CD3 on CD28+ CD45RA+ CD8br, PDL-1 on CD14- CD16-, and CD4 on CD39+ secreting Treg (all FDRs < 0.05). Prostatitis was also found to be significantly linked with 11 immunophenotypes, containing CD25 on IgD+ CD38- unsw mem, CD38 on CD3- CD19-, CD3 on naive CD8br, CD3 on Naive CD4+ , CD3 on CD39+ CD4+ , CD3 on CD4+ , CD14 on CD14+ CD16- monocyte, CD4 on CM CD4+ , CD4 on naive CD4+ , CD4 on CD45RA+ CD4+ , and CD4 on secreting Treg (all FDRs < 0.05). CONCLUSIONS: Our results suggest important associations between prostatitis and immune cell profiles, shedding light on the immune-related etiologies and phenotypes in prostatitis.
An L-shaped curve relating Hs-CRP/HDL-C(CHR) index to kidney stone disease (KSD) in US adult participants: a cross-sectional study.
Shi B, Yuan W, Liu S … +3 more , Dai Y, Sun X, Jia Y
Aging Male · 2026 Dec · PMID 41904603 · Publisher ↗
Using 2015-2020 NHANES data, this cross‑sectional study examined the association between the Hs‑CRP/HDL‑C index (CHR) and adult kidney stone disease (KSD) and its potential nonlinear dose-response pattern. Weighted multi...
Using 2015-2020 NHANES data, this cross‑sectional study examined the association between the Hs‑CRP/HDL‑C index (CHR) and adult kidney stone disease (KSD) and its potential nonlinear dose-response pattern. Weighted multivariable logistic regression and spline analyses were applied. Overall KSD risk was 10%; CHR showed a positive association with KSD odds (OR = 1.04, 95% CI = 1.01-1.08, < 0.05). Smooth curves revealed an L‑shaped relationship ( for nonlinearity <0.05), with a steep increase when CHR <0.358, then plateauing. An interaction with albumin level was observed ( < 0.05); subgroup analyses by age, sex, BMI, smoking, alcohol, and triglycerides showed no significant differences. These findings suggest CHR may aid KSD risk assessment, but prospective studies are needed to confirm causality and temporal sequence.
Association between COVID-19 status and Leydig cell functional capacity among men in hospitalized cohorts.
Anand-Ivell R, Yang X, Tarr AW … +6 more , Irving WI, Clark DJ, Staines HM, Augustin Y, Krishna S, Ivell R
Aging Male · 2026 Dec · PMID 41902764 · Publisher ↗
BACKGROUND: The first wave of the COVID-19 pandemic in the UK in 2020 led to significant morbidity, hospitalization, and death, particularly amongst elderly men. Recent meta-analyses confirmed that SARS-CoV-2 infection l...
BACKGROUND: The first wave of the COVID-19 pandemic in the UK in 2020 led to significant morbidity, hospitalization, and death, particularly amongst elderly men. Recent meta-analyses confirmed that SARS-CoV-2 infection led to reduced testosterone and increased LH, suggestive of testicular Leydig cell involvement. METHODS: The unique Leydig cell biomarker insulin-like peptide 3 (INSL3) was measured in two cohorts of hospitalized men in Nottingham and London with moderate to severe COVID-19 symptoms. RESULTS: For Nottingham men, circulating INSL3 was reduced at entry (0.36 0.34 ng/ml; = 143), indicative of primary hypogonadism, but appeared to recover to normal values after treatment. For the less severely affected London men, INSL3 at entry was within the normal range (0.89 0.30 ng/ml; = 43), though sequential blood sampling suggested a small decline thereafter, which recovered with treatment. CONCLUSION: In this first study of the biomarker INSL3 in hospitalized men with COVID-19, the results identify a Leydig cell deficiency and consequent hypogonadism as integral to the symptoms of the illness, which was most marked in severely ill patients. In most cases, Leydig cells appeared to recover with treatment. Whether Leydig cells are directly affected by SARS-CoV-2 virus or indirectly via systemic inflammation is unclear, though both are likely.
Correlations between the cumulative metabolic score for visceral fat and its dynamic trajectories with the onset of cardiovascular disease in middle-aged and older adults: findings from two prospective cohorts.
Xu L, Sun M
Aging Male · 2026 Dec · PMID 41902643 · Publisher ↗
BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of global mortality. The metabolic score for visceral fat (Mets-VF) integrates metabolic dysfunction and visceral adiposity, yet the effects of its long-te...
BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of global mortality. The metabolic score for visceral fat (Mets-VF) integrates metabolic dysfunction and visceral adiposity, yet the effects of its long-term cumulative exposure (cuMets-VF) and dynamic trajectories on CVD risk remain underexplored. METHODS: This prospective cohort study included participants from the China Health and Retirement Longitudinal Study (CHARLS; = 4,281) and the English Longitudinal Study of Ageing (ELSA; = 1,071). Mets-VF trajectories were identified using K-means clustering. Incident CVD was ascertained during follow-up. Cox proportional hazards models were applied to evaluate associations. RESULTS: Over a median follow-up of approximately 5.0 years in CHARLS and 9.0 years in the ELSA, higher cuMets-VF levels and adverse trajectories were significantly associated with an increased CVD risk. Each unit increase in cuMets-VF was associated with a 14% higher risk of CVD in CHARLS (HR = 1.14, 95% CI: 1.07-1.22) and a 13% higher risk in ELSA (HR = 1.13, 95% CI: 1.01-1.26). Participants in the high-risk stable trajectory showed the highest cumulative CVD incidence (21.7% in CHARLS and 21.5% in ELSA). CONCLUSION: Long-term cumulative exposure to elevated Mets-VF and persistently adverse trajectories are robust predictors of incident CVD in middle-aged and older adults.
Age-related patterns in prostate cancer: epidemiology, pathology, treatment, and survival.
Zhang X, Wang C, Pan S … +1 more , Sun W
Aging Male · 2026 Dec · PMID 41891526 · Publisher ↗
BACKGROUND: Contemporary, systematic comparisons of prostate cancer (PCa) across the entire age spectrum regarding incidence, pathology, treatment, and long-term outcomes remain lacking. METHODS: Patients were identified...
BACKGROUND: Contemporary, systematic comparisons of prostate cancer (PCa) across the entire age spectrum regarding incidence, pathology, treatment, and long-term outcomes remain lacking. METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database to assess age-related differences in pathological features, treatment patterns, and cancer-specific survival (CSS), with additional analyses accounting for competing risks from other-cause mortality. RESULTS: Older age was associated with lower stage risk but higher PSA, ISUP grade, and overall disease risk (20-55 as reference; 56-65, OR = 1.29, 95% CI, 1.27-1.32, < 0.001; 66-75, OR = 1.67, 95% CI, 1.64-1.71, < 0.001; 76-85, OR = 3.10, 95% CI, 3.03-3.18, < 0.001). In nonmetastatic patients, the likelihood of receiving definitive treatment and choosing radical prostatectomy decreases with age. Overall, CSS worsened with age; however, the 56-65 years group showed no significant difference compared with the 20-55 years reference group (HR = 1.00, 95% CI, 0.95-1.06, = 0.872), whereas the older age groups presented progressively poorer CSS (66-75, HR = 1.16, 95% CI, 1.10-1.23, < 0.001; 76-85, HR = 1.72, 95% CI, 1.62-1.82, < 0.001). After accounting for other-cause mortality using a competing-risk model, similar patterns were observed. CONCLUSION: PCa is increasingly diagnosed in older men, with higher age associated with earlier-stage presentation but more adverse pathology, less frequent radical prostatectomy, and risk-dependent survival effects across age groups.
A systems biology approach to identify common molecular signatures in Hashimoto's thyroiditis and rheumatoid arthritis.
Wei JB, Lin Y, Xu QY … +1 more , Lin LP
Aging Male · 2026 Dec · PMID 41891206 · Publisher ↗
BACKGROUND: Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) are prevalent autoimmune disorders with substantial clinical overlap, yet the shared molecular mechanisms underlying their comorbidity remain poorly...
BACKGROUND: Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) are prevalent autoimmune disorders with substantial clinical overlap, yet the shared molecular mechanisms underlying their comorbidity remain poorly understood. MATERIALS AND METHODS: Publicly available GEO datasets were analyzed to identify differentially expressed genes (DEGs) and hub genes. Functional enrichment analysis was performed to characterize biological processes associated with these DEGs. Single-sample gene set enrichment analysis (ssGSEA) was applied to assess immune cell infiltration patterns. A transcription factor‑mRNA‑microRNA (TF-mRNA-miRNA) regulatory network was constructed to pinpoint key regulators, and drug target prediction was conducted via the QuartataWeb platform. RESULTS: Bioinformatics analysis of the GEO dataset identified 196 DEGs, including 10 hub genes. Enrichment analyses linked the DEGs to pathways involved in inflammation and immune regulation. ssGSEA revealed that activated B cells play a central role in disease pathogenesis. The regulatory network identified multiple critical modulators, and drug target analysis computationally predicted CD2, CTLA4, and CD27 as potential therapeutic targets. CONCLUSION: Our study findings suggest that the disruption of immune tolerance and aberrant immune activation are likely the primary mechanisms driving the comorbidity of HT and RA. The identified hub genes and their potential druggable targets provide a theoretical basis for subsequent experimental validation and the development of precision therapeutic strategies.
Real-world outcomes of tadalafil plus mirabegron combination therapy in men with lower urinary tract symptoms and overactive bladder symptoms: a retrospective cohort study.
İnkaya A, Güngör HS
Aging Male · 2026 Dec · PMID 41879268 · Publisher ↗
BACKGROUND: Men with mixed lower urinary tract symptoms (LUTS) often have storage symptoms that drive bother and quality-of-life impairment. Evidence on tadalafil plus mirabegron in routine clinical practice is limited....
BACKGROUND: Men with mixed lower urinary tract symptoms (LUTS) often have storage symptoms that drive bother and quality-of-life impairment. Evidence on tadalafil plus mirabegron in routine clinical practice is limited. OBJECTIVE: To determine whether tadalafil plus mirabegron was associated with clinically meaningful within-person improvement in IPSS and OABSS in men with mixed LUTS and overactive bladder (OAB) symptoms. METHODS: A single-centre retrospective cohort study of 50 men treated with tadalafil 5 mg plus mirabegron 50 mg. The primary endpoints were within-person change in International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). Secondary endpoints included bladder diary variables, maximum urinary flow rate (Qmax), post-void residual (PVR) volume, International Index of Erectile Function-5 (IIEF-5), and NIH-Chronic Prostatitis Symptom Index (NIH-CPSI). RESULTS: Symptoms improved after combination therapy, but the OABSS response was less consistent than the IPSS response. Mean IPSS decreased by 4.18 points (95% CI -4.86 to -3.54; r_rb = -1.00; two-sided < 0.001) and mean OABSS decreased by 1.86 points (95% CI -2.22 to -1.50; r_rb = -1.00; two-sided < 0.001). Clinically meaningful IPSS improvement occurred in 38 of 50 men, or 76.0% (95% CI 62.6% to 85.7%); clinically meaningful OABSS improvement occurred in 17 of 50, or 34.0% (95% CI 22.4% to 47.8%). Dual response was seen in 15 of 50 men, or 30.0% (95% CI 19.1% to 43.8%). IIEF-5 increased by 2.92 points (95% CI 2.14 to 3.70; r_rb = 0.86; two-sided < 0.001). Adverse events were recorded in 3 of 50 men, or 6.0% (95% CI 2.1% to 16.2%), and no patient developed acute urinary retention. CONCLUSIONS: In men with mixed LUTS and prominent storage symptoms, tadalafil plus mirabegron was associated with improvement in overall symptom burden, bladder diary measures, and erectile-function scores without an obvious retention signal. The clinical benefit was clearer for IPSS than for OABSS, so early reassessment is important to identify men who do not improve.
Evaluating the safety profile of α-1 blockers, 5α-reductase inhibitors, and PDE5I for BPH: a disproportionality analysis of real-world adverse events based on FDA adverse event reporting system (FAERS).
Zhao Z, Wu C, Xiong Y … +3 more , Wang W, Qin F, Yuan J
Aging Male · 2026 Dec · PMID 41876378 · Publisher ↗
OBJECTIVE: To compare the real-world safety profiles of α1-adrenoceptor antagonists (α1-blockers), 5α-reductase inhibitors (5ARIs), and phosphodiesterase type 5 inhibitor (PDE5I) used in the treatment of benign prostatic...
OBJECTIVE: To compare the real-world safety profiles of α1-adrenoceptor antagonists (α1-blockers), 5α-reductase inhibitors (5ARIs), and phosphodiesterase type 5 inhibitor (PDE5I) used in the treatment of benign prostatic hyperplasia (BPH). METHODS: This retrospective pharmacovigilance study analyzed FDA Adverse Event Reporting System (FAERS) from Q1 of 2004 to Q2 of 2025. Reports of adverse events (AEs) in male BPH patients receiving AUA guideline-recommended drugs including α-1 blockers (tamsulosin, silodosin, doxazosin, and alfuzosin), 5ARIs (finasteride and dutasteride), and tadalafil were extracted. Disproportionality analysis was performed to detect significant safety signals. AEs were classified using MedDRA terms. RESULTS: Among 9,540 unique reports and 25,796 AEs entries, patients aged 65-80 years accounted for the majority of the reports. Most AEs occurred within 30 days of treatment initiation. Hospitalization was the most common serious outcome. Sixteen significant AEs were detected, including pollakiuria, gynecomastia, breast pain and so on, with distinct reporting patterns across drug classes. CONCLUSIONS: This large-scale pharmacovigilance analysis identified distinct post-marketing safety signals among guideline-recommended pharmacotherapies for BPH, confirming known risks and suggesting potential novel adverse-event signals warranting further investigation.
Development and validation of machine learning prognostic models for overall survival in non-surgical prostate cancer patients with bone metastases.
Yang Q, Wang B, Yang Y … +4 more , Li S, Li Y, Du Q, Bao E
Aging Male · 2026 Dec · PMID 41839858 · Publisher ↗
OBJECTIVE: To construct and interpret a machine learning model for predicting overall survival in nonsurgical prostate cancer with bone metastases (PCBM). METHODS: Data from 3,378 SEER database patients were utilized to...
OBJECTIVE: To construct and interpret a machine learning model for predicting overall survival in nonsurgical prostate cancer with bone metastases (PCBM). METHODS: Data from 3,378 SEER database patients were utilized to develop machine learning survival models, with the best-performing model visually interpreted using SHAP. RESULTS: The Extra Survival Trees (EST) model performed best (validation AUC = 0.694, C-index = 0.643). SHAP analysis identified the Gleason score as the most critical survival factor, significantly outweighing clinical T stage. Visceral metastasis and advanced age also markedly increased mortality risk. CONCLUSION: The EST model effectively assesses OS in nonsurgical PCBM. The Gleason score holds greater prognostic value than local anatomical staging in this cohort, suggesting clinicians should prioritize early, aggressive combination treatments for high-Gleason, high-burden patients.
Immune-mediated pathways between red blood cell traits and prostate cancer: a causal relationship network based on Mendelian randomization evaluation.
Yang T, Zhang J, Li J … +2 more , Yan Q, Li J
Aging Male · 2026 Dec · PMID 41839839 · Publisher ↗
BACKGROUND: Although both the immune and hematopoietic systems play important roles in prostate cancer (PCa), few studies have comprehensively investigated the combined influence of these systems on PCa risk. METHOD: The...
BACKGROUND: Although both the immune and hematopoietic systems play important roles in prostate cancer (PCa), few studies have comprehensively investigated the combined influence of these systems on PCa risk. METHOD: The datasets used to construct causal networks for evaluation via Mendelian randomization and mediation Mendelian randomization (MMR). Nine analytical approaches were applied to evaluate the causal associations. RESULT: The findings revealed that red blood cell count (RBC) and red cell distribution width (RDW) were related to a modest increased risk of PCa, while mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were related to a modest reduced risk. Further, MMR analyses identified that HLA-DR on dendritic cells mediated the causal effect of RBC on PCa, with a mediated proportion of 12.09%, and that IgD CD38 B cell % B cell mediated the effects of RDW and MCHC on PCa, with mediating proportions of 15.07% and 25.96%, respectively. Moreover, the IgD CD38 B cell % lymphocytes mediated the causal effect of MCHC on PCa, with a mediated proportion of 29.03%. CONCLUSION: RBC, RDW, MCH, and MCHC were related to the risk of PCa. Immune cells act as major mediators in this relationship.
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