Search Results (1,003)

The widespread consumption of ultra-processed foods increases exposure to advanced glycation end-products (AGEs), key mediators of oxidative stress and chronic low-grade inflammation. Although AGEs contribute to adult metabolic dysfunction, their early molecular correlates in pediatric populations remain insufficiently defined. Extracellular vesicle (EV)-associated miRNAs represent stable, non-invasive indicators of systemic stress responses. This study evaluated the association between urinary AGEs and urinary EV-associated miRNAs in 94 Italian children and adolescents from the I.Family cohort. Fluorescent AGEs were quantified via spectrofluorimetry, and EV-enriched urinary miRNAs were profiled using next-generation sequencing. Differential expression and multivariable generalised linear models (adjusted for age, sex, BMI z-score, and hs-CRP) were performed. Differential expression analysis revealed a significant upregulation of hsa-miR-4516 in participants with high versus low urinary AGE levels (fold change = 2.31; FDR = 0.024). In multivariable continuous models, hsa-miR-4516 remained the primary AGE-associated miRNA, though the association attenuated following adjustment for BMI z-score and hs-CRP. Functional enrichment and network analyses highlighted pathways governing oxidative stress responses, proteostasis, and cellular survival. Overall, urinary EV-associated miRNAs may reflect coordinated biological responses to dietary AGE burden rather than serving as direct exposure biomarkers, offering integrated, non-invasive insights into early metabolic and inflammatory adaptations in children. Full article

Heart failure (HF) is a complex clinical syndrome that represents an increasingly relevant health issue, associated with substantial morbidity and mortality in pediatric patients. While considerable therapeutic advances have transformed the prognosis of adult patients with heart failure over the past three decades, progress in pediatric heart failure has been considerably slower. In adult patients, large randomized controlled trials (RCTs) have established angiotensin-converting enzyme inhibitors (ACE inhibitors), beta-blockers, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and, more recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors as the cornerstone of guideline-directed medical therapy. Evidence supporting pharmacological therapy in pediatric heart failure remains scarce and frequently inconclusive, with most available studies being limited by small sample sizes and heterogeneous patient populations. Therefore, heart failure treatment in children is mostly extrapolated from adult studies and guidelines. However, developmental differences in myocardial structure and function, neurohormonal signaling, pharmacokinetics and pharmacodynamics may substantially influence therapeutic response. In addition, the rarity and the etiological heterogeneity of pediatric HF create major methodological challenges for adequately powered clinical trials. This review compares the pharmacological management of HF in adult and pediatric populations, examines the strength of evidence for contemporary therapies and discusses the biological and methodological limitations of translating adult evidence into pediatric practice. Multicenter collaborative studies and well-designed pediatric randomized controlled trials are essential for establishing truly evidence-based pharmacological strategies for children with HF. Full article

Background/Objectives: Menstrual health in adolescence is influenced by nutritional, developmental, and psychosocial factors, yet integrated school-based evidence from Central Asia is limited. We assessed recorded anthropometric, menstrual/reproductive, and psychosocial indicators among adolescent girls in southern Kazakhstan and evaluated factors associated with a prespecified composite menstrual/reproductive outcome. Methods: We conducted a cross-sectional secondary analysis of a non-public school health screening database containing 5197 participant records from 2025. After removal of 946 exact duplicate copies, 4251 unique records of girls aged 12–18 years remained. We present prevalence estimates with Wilson 95% confidence intervals (CIs). We estimated adjusted prevalence ratios (aPRs) using modified Poisson regression with robust standard errors clustered by recorded school field. Results: Mean age was 15.03 ± 1.23 years and mean BMI was 20.36 ± 3.36 kg/m². The source form used fixed adult BMI categories; these are reported descriptively and are not interpreted as pediatric nutritional diagnoses. At least one non-reference menstrual or reproductive indicator was recorded in 24.1% of participants; severe menstrual pain and stress were each recorded in 6.9%. Stress was associated with any menstrual/reproductive abnormality (aPR 2.05, 95% CI 1.65–2.54) and with severe menstrual pain (aPR 3.27, 95% CI 2.39–4.46). Unsatisfactory nutrition was also associated with the composite outcome (aPR 1.64, 95% CI 1.35–2.00). Conclusions: Recorded menstrual/reproductive concerns were frequent in this screened sample, and stress showed consistent associations with menstrual outcomes. Because anthropometric categories were based on adult cut points and several screening items were not validated instruments, interpret the findings as descriptive and hypothesis-generating rather than as population prevalence or causal estimates. Full article

The rise of multidrug-resistant (MDR) pathogens in the pediatric population represents a significant global health challenge, compounded by a historically stagnant antibiotic pipeline for children. While several novel antibiotics have been approved for adults in recent decades, pediatric labeling is often deferred due to the complexities of developmental pharmacology and due to a certain precautionary prudence in introducing new drugs onto the market for this population. This review explores the landscape of the most recent antibiotics, including advanced cephalosporins (ceftaroline, cefiderocol, and ceftobiprole), novel beta-lactam/beta-lactamase inhibitor combinations (e.g., ceftazidime/avibactam, meropenem/vaborbactam), and long-acting lipoglycopeptides. We analyze their approval trials, pediatric-specific PK/PD profiles, and the balance between on-label use and evidence-based off-label prescriptions. Furthermore, we emphasize the role of antimicrobial stewardship through the “3 D’s” rule and the evolution of Therapeutic Drug Monitoring (TDM) from reactive safety controls to proactive, model-informed precision dosing (MIPD). Finally, we advocate for a multidisciplinary synergy between pediatricians and pharmacologists as the cornerstone for optimizing outcomes and preserving the efficacy of the future antibiotic pipeline. Full article

Non-cirrhotic portal hypertension (NCPHT) is defined as portal hypertension (PHT) occurring in the absence of cirrhosis. Major etiological causes of NCPHT include immunological disorders, chronic infections, exposure to medications or toxins, prothrombotic conditions, and several genetic syndromes, highlighting that NCPHT is not a single disease but a shared phenotype arising from diverse underlying pathways. NCPHT is frequently misdiagnosed, largely due to inconsistent nomenclature and limited scientific literature. The broader term non-cirrhotic portal fibrosis (NCPF) or porto-sinusoidal vascular disease (PSVD) includes patients in a preclinical stage who demonstrate histological features similar to NCPHT but lack clinical evidence of PHT. Early detection is linked to a favorable prognosis and improved clinical outcomes. Management strategies in pediatrics continue to rely on extrapolations from adult practice, with sparse evidence to guide pediatric care. Liver biopsy remains the cornerstone of diagnosis, demonstrating nodular regenerative hyperplasia, obliterative portal venopathy, or incomplete septal fibrosis. Management focuses on prophylactic and symptomatic care, with endoscopic therapy for controlling variceal bleeding. Porto-systemic shunts and, ultimately, liver transplantation therapies may be needed for advanced stages. A pressing need exists for standardized diagnostic criteria and multicenter studies to define natural history, refine risk stratification, and evaluate therapeutic approaches in the pediatric population. This review provides an overview of the pediatric causes of NCPHT, outlines the current understanding of pathophysiology, and discusses the clinical presentations and management strategies, while highlighting existing research gaps. Full article

Severe pediatric asthma remains a significant clinical challenge despite advances in conventional therapy. Some children continue to experience persistent symptoms, recurrent exacerbations, and substantial morbidity despite optimized treatment with inhaled corticosteroids and long-acting bronchodilators. Advances in the understanding of asthma immunopathology, particularly type 2 (T2) inflammation, have led to the development of targeted biologics that modulate key inflammatory pathways. Several monoclonal antibodies are now approved for pediatric use, including the anti-immunoglobulin E (IgE) agent omalizumab, anti-interleukin (IL)-5 therapies such as mepolizumab, and the IL-4 receptor antagonist dupilumab. These biologics significantly reduce exacerbation rates, improve lung function, and decrease dependence on systemic corticosteroids in selected pediatric populations. Their effective use, however, requires careful assessment of clinical phenotypes and biomarkers, including blood eosinophils, serum IgE, and fractional exhaled nitric oxide. Uncertainties remain regarding treatment sequencing, duration, long-term safety, and cost-effectiveness. Agents targeting upstream epithelial cytokines, including tezepelumab, are broadening the therapeutic landscape. Despite this progress, pediatric evidence remains fragmented across age groups, biologic agents, study designs, and real-world cohorts, while many reviews focus on individual therapies or partly extrapolate from adult data. This review synthesizes pediatric evidence on efficacy, safety, biomarker-guided selection, age-related indications, and implementation challenges across approved and emerging biologics. It aims to provide clinicians with a practical framework for treatment selection and monitoring while identifying priorities for future pediatric research. Full article

Pain in children remains frequently underrecognized and undertreated despite significant advances in pediatric analgesia. The pharmacologic management of pediatric pain is challenging due to developmental differences in pharmacokinetics and pharmacodynamics, variability in drug metabolism, age-dependent responses, and the limited availability of high-quality pediatric clinical trials. This narrative review summarizes current evidence regarding the pharmacologic management of nociceptive, neuropathic, and nociplastic pain in children, integrating developmental pharmacology, efficacy data, safety considerations, and limitations of available evidence. A mechanism-based classification of pain provides a useful framework for therapeutic decision-making; however, clinical conditions often involve overlapping mechanisms requiring individualized and multidisciplinary approaches. Evidence supporting pharmacological interventions varies considerably according to pain type. Acetaminophen and NSAIDs remain the most used agents for nociceptive pain, while opioids retain a role in selected cases of moderate-to-severe pain under careful monitoring. Management of neuropathic and nociplastic pain remains particularly challenging due to limited pediatric trials, frequent off-label prescribing, and reliance on extrapolation from adult populations. Future research should focus on age-specific randomized controlled trials, pharmacokinetic and pharmacogenomic variability, long-term safety outcomes, and integration of pharmacologic treatments within multimodal pain management strategies. Full article

Sleep architecture alterations have been shown in major psychiatric disorders, but the contribution of demographic factors to between-study heterogeneity remains insufficiently characterized. This study reports a transdiagnostic systematic review and meta-regression of case-control polysomnographic studies comparing schizophrenia, bipolar disorder, and unipolar depression with healthy controls. The factors age and sex as possible moderators across harmonized case-control polysomnographic studies have been analyzed. Eligible studies reported diagnostic criteria, treatment status, age, and sex. Because the UD literature encompassed developmentally distinct populations, pediatric/adolescent and adult studies were analyzed separately. Standardized mean differences were synthesized using random-effects models with REML estimation. Univariable mixed-effects meta-regressions assessed study-level mean age and sex composition as moderators within each diagnostic group. Study-level mean age and sex composition significantly moderated delta sleep effect sizes in drug-naive schizophrenia, while study-level mean age significantly moderated REM time in drug-free schizophrenia. In bipolar disorder, study-level mean age moderated REM sleep time effect sizes during mania, whereas sex composition moderated delta sleep and REM density effect sizes. In UD, study-level mean age moderated total sleep time, and sex composition moderated wake after sleep onset only in pediatric/adolescent studies, whereas no significant moderation was observed in adult samples. No significant moderator effects were identified during bipolar depression. Overall, demographic composition explained only a modest proportion of between-study heterogeneity. Interpretation is limited by the ecological nature of study-level meta-regression and residual study heterogeneity. Full article

Background: Arterial ischemic stroke (AIS) is not common in pediatric patients; however, it causes significant morbidity and mortality. Reperfusion therapies, including intravenous thrombolysis (IVT) and endovascular mechanical thrombectomy (EVT) are established standards of care in selected adults with acute ischemic stroke; however, their safety and functional outcomes in the pediatric population remain poorly defined. Objective: To assess the safety and functional outcomes of reperfusion therapies in children with AIS. Methods: A systematic search was conducted across major databases including PubMed, Medline, Scopus, Embase, Web of Science, and Cochrane Library. Studies reporting on pediatric patients aged 18 years or less treated with IVT, EVT, or both for acute AIS were included. The primary safety outcome was the risk of developing symptomatic intracerebral hemorrhage (sICH). Primary functional outcomes were 90-day functional independence, measured via the Pediatric Modified Rankin Scale (Ped-mRS ≤ 2) or Pediatric Stroke Outcome Measure (PSOM ≤ 1). Secondary outcomes measured included successful recanalization (Modified Thrombolysis in Cerebral Ischemia [mTICI] grade 2b/3), and death due to any cause at 90 days. Results: Successful angiographic recanalization evaluated across thrombectomy and bridging arm cohorts revealed high success rate with the pooled proportion of 87.4% (95% CI: 79.1–93.9%). Reperfusion therapies are associated with significant early neurological recovery and favorable 90-day functional outcomes (Ped-mRS 0–2 achieved in a substantial majority of treated cohorts), when compared to the best medical treatment (BMT) controls. The overall rate of sICH remains low (<2%), demonstrating a much better safety profile comparable to adult benchmarks. Conclusions: Acute reperfusion therapies in pediatric AIS are associated with high rates of recanalization and favorable functional outcomes and had low observed rates of symptomatic intracranial hemorrhage in selected pediatric observational cohorts. However, given the absence of randomized controlled trials, these findings reflect observational associations and must be interpreted with appropriate clinical caution. Therefore, there is need for further prospective international studies capable of generating higher-quality evidence to guide future pediatric stroke management. Full article

Background: Melioidosis is a potentially life-threatening infection caused by Burkholderia pseudomallei. Hepatic and splenic involvement are recognized manifestations of disseminated melioidosis; however, reported prevalence varies considerably across studies, and no quantitative synthesis has been available. This systematic review and meta-analysis aimed to estimate the pooled prevalence of hepatic, splenic, and concomitant hepatosplenic involvement in patients with melioidosis. Methods: A systematic search of PubMed, Embase, and Scopus was conducted from database inception to May 2026, following the PRISMA 2020 guidelines. Observational studies reporting hepatic and/or splenic involvement among patients with confirmed melioidosis were eligible. Random-effects meta-analyses were performed to estimate pooled prevalence with 95% confidence intervals (CIs). Subgroup analyses were conducted according to geographic region and age group. Methodological quality was assessed using the Joanna Briggs Institute critical appraisal checklist. Results: Fourteen eligible studies involving 1844 patients with melioidosis were included. The pooled prevalence of hepatic involvement was 11% (95% CI, 6–18%; I² = 84.8%), splenic involvement was 15% (95% CI, 7–27%; I² = 95.8%), and concomitant hepatosplenic involvement was 13% (95% CI, 4–34%; I² = 89.5%). Subgroup analyses demonstrated significantly higher pooled prevalence of hepatic and splenic involvement in Southeast Asia than in Oceania (p = 0.0164 and p = 0.0003, respectively). No significant differences were observed between adult and pediatric populations for hepatic (p = 0.1607) or splenic involvement (p = 0.8243). Most included studies were judged to have a moderate risk of bias, and no evidence of small-study effects was identified for analyses of hepatic or splenic involvement. Conclusions: Hepatic and splenic involvement are common manifestations of melioidosis, affecting approximately one in nine and one in seven patients, respectively. Significant geographic variation suggests that disease burden is greater in Southeast Asia than in Oceania. These findings support the routine consideration of abdominal imaging in patients with suspected or confirmed melioidosis, particularly in endemic regions, to facilitate early recognition of visceral involvement. Further prospective multicenter studies using standardized imaging protocols are needed to refine prevalence estimates and improve understanding of hepatosplenic melioidosis. Full article

Primary ciliary dyskinesia (PCD) is an inherited motile-cilia disorder. Impaired mucociliary transport promotes persistent secretion retention, infection, inflammation, and bronchiectasis. The central treatment problem is therefore failure of airway clearance rather than infection alone. This narrative review evaluates airway clearance techniques (ACTs), mucoactive adjuncts, and pulmonary rehabilitation for children and adolescents. We prioritize direct pediatric PCD evidence, identify mixed-age or adult PCD findings as population-bound PCD evidence, and label pediatric bronchiectasis and cystic fibrosis evidence as indirect. Because no ACT has been shown to be universally superior and pediatric rehabilitation evidence remains limited, we present an author-proposed clearance-anchored dual-pillar framework. ACTs directly address mucus retention. Pulmonary rehabilitation complements ACT by targeting fitness, muscle performance, participation, and self-management. Response should be assessed across four domains: clinical stability, treatment performance, physiological and functional outcomes, and patient and family experience. Prospective multicenter comparative trials and harmonized pediatric outcome measures are urgently needed. Full article

Background/Objectives: Pediatric solid tumors (PST) are a biologically distinct group of malignancies whose developmental origins and molecular drivers differ substantially from those of adult cancers, with direct implications for therapeutic strategy and clinical outcome. This review synthesizes current evidence on molecular pathogenesis, tumor microenvironment biology, and the structural conditions that shape access to care across select PST. Methods: A narrative review of peer-reviewed literature was conducted primarily using PubMed, supplemented by Google Scholar, covering publications from 2000 to 2025. Tumor types were selected based on their prevalence in the pediatric population and the availability of evidence addressing both molecular features and health disparities. Body: Across eight tumor types (neuroblastoma, Ewing sarcoma, pediatric brain tumors, rhabdomyosarcoma, Wilms tumor, retinoblastoma, osteosarcoma, and chondrosarcoma), recurrent molecular alterations including MYCN amplification, EWS-FLI1 fusions, PAX-FOXO1 rearrangements and IDH 1/2 mutations emerge as central determinants of disease behavior and eligibility for treatment. The tumor microenvironment manifests as a shared mediator of immune exclusion and therapeutic resistance across tumor types, with, but not limited to, tumor-associated macrophages, myeloid-derived suppressor cells, and checkpoint molecule expression, identified as recurrent features influencing treatment response. Immunotherapeutic strategies have shown variable efficacy across PST, with the most consistent clinical benefit established in neuroblastoma. A critical and underappreciated pattern stands out across tumor types: children carrying the most aggressive molecular subtypes are disproportionately those with the least access to therapies those subtypes demand, emphasizing an overlap of biological and structural disadvantage that is also amplified in low- and middle-income countries, where late-stage presentation, treatment abandonment and limited access to molecular diagnostics compound the biological disadvantage. Conclusions: Within the eight PST reviewed, the most aggressive molecular subtypes and the greatest structural disadvantages converge in the same children; those carrying MYCN amplification, PAX-FOXO1 fusions, or EWS-FLI1 fusions are disproportionately those with the least access to the therapies their biology demands. Genomic and immunologic advances will only reach their full clinical potential when paired with inclusive trial data, diversified genomic databases, and most importantly, equitable access to biomarker-specialized therapies across all populations. Full article

Background: The dynamic advancement of pediatric hemato-oncology and intensified therapeutic protocols have significantly increased survival rates while simultaneously highlighting the challenge of long-term treatment complications. Within the cohort of adolescent and young adult (AYA) survivors, delayed neurocognitive deficits, often manifesting as the chemobrain phenotype, and psychosocial disorders constitute a particularly substantial burden. Contemporary neurogastroenterological evidence indicates a fundamental role of persistent dysbiosis and gut–brain axis dysfunction in the pathogenesis of these alterations. This review aims to critically synthesize translational evidence elucidating the impact of iatrogenic gut microbiota damage and modifiable dietary patterns on the development of long-term neurocognitive sequelae in survivors of early childhood cancer. Methods: A systematized narrative review was conducted in accordance with the SANRA guidelines by integrating data from in vivo models and observational studies. A comprehensive literature search across the PubMed, Embase, Cochrane Central, Scopus, and Web of Science databases up to June 2026 was performed utilizing the Population, Exposure, and Outcomes (PEO) framework. Results: Oncological therapies, including myeloablative conditioning and broad-spectrum antibiotic therapy, induce a microbial scar phenomenon characterized by the depletion of commensal Firmicutes in favor of resistant pathobionts. The subsequent decline in the synthesis of neuroprotective short-chain fatty acids (SCFAs) alongside the pathological activation of the kynurenine pathway disrupts central nervous system homeostasis. Translocation of lipopolysaccharides (LPSs) across the compromised intestinal barrier generates systemic inflammation recognized as inflammaging, which, in turn, stimulates neurotoxic microglial hyperreactivity. This pathophysiological cascade is accelerated by a pro-inflammatory Western diet, whereas anti-inflammatory interventions such as the MIND diet and postbiotics demonstrate measurable restorative potential. Conclusions: The pathophysiology of delayed neurotoxicity is largely a consequence of systemic neuroinflammation driven by intestinal dysbiosis. Implementing individualized dietary and microbiome-targeted strategies into survivorship care protocols constitutes a crucial direction for clinical prophylaxis. Validating their clinical efficacy in the AYA population necessitates prospective randomized controlled trials integrated with shotgun metagenomic sequencing. Full article

Background/Objectives: Exercise medicine is gaining significant importance in adult oncology to improve physical activity and quality of life (QoL). However, few studies have investigated the effects of adapted physical activities in the pediatric population. The aim of this secondary analysis is to compare the movement quality of a hematological/oncological pediatric population before and after an individualized exercise program (IEP). Methods: Participants who met the inclusion criteria (aged 5–18 years, oncological/hematological diagnosis, consent) underwent an IEP delivered both in the hospital and via telemedicine at home. The subject’s movement quality was assessed before and after six months of the IEP using instrumented functional tests (i.e., 6 min walking test, Timed Up and Go, T25-FW, and turning test). To reduce the number of variables obtained, principal component analysis (PCA) was performed, and the resulting scores were then compared. Results: A total of 18 subjects (median age 12 years; eight females) were included in the analysis. Through the PCA, four dimensions were identified: Gait Efficiency, Gait Quality, Dynamic Balance, and Functional Abilities. The pre–post comparison showed significant improvements (p = 0.002) in Dynamic Balance and a trend (p = 0.05) in Gait Efficiency. Conclusions: The presented results indicate the crucial Principal Components (PCs) of movement in children treated for cancer. Moreover, in our setting, under the IEP we observed a significant improvement in Dynamic Balance. The results are consistent with those observed in previous studies. However, the limited number of subjects and the study design preclude definitive conclusions. Full article

Background/Objectives: Male hypogonadism affects 35–50% of men with type 2 diabetes mellitus (T2DM) and obesity. The relationship between testosterone deficiency and response to incretin-based therapies (GLP-1 and GIP receptor agonists) remains incompletely understood. This systematic literature review, conducted following PRISMA 2020 guidelines, examines whether male hypogonadism represents a risk factor for poor response to incretin therapy or, conversely, whether these agents offer therapeutic benefits for this population. Methods: A comprehensive systematic literature search was conducted on 31 December 2024, across PubMed/MEDLINE, Scopus, and Web of Science using three search domains: (1) hypogonadism and incretin therapy response; (2) testosterone deficiency and GLP-1/GIP receptor agonists; (3) incretin response and testosterone. Eligibility criteria included human studies (randomized controlled trials [RCTs], observational studies, cohort studies, cross-sectional studies, systematic reviews, and meta-analyses) in adult men reporting testosterone levels and/or incretin response. Animal studies, pediatric populations, case reports with n < 5, editorials, and letters without data were excluded. Study selection followed PRISMA 2020 guidelines with independent dual screening. Risk of bias was assessed using the Cochrane Risk-of-Bias 2.0 tool (ROB2) for RCTs, the Newcastle–Ottawa Scale (NOS) for observational studies, and AMSTAR-2 for systematic reviews and meta-analyses. Due to substantial heterogeneity in study designs, populations, interventions, and outcome measures, a meta-analysis was not feasible; therefore, a narrative synthesis was performed. Results: From 326 records identified, 29 studies were included after deduplication and screening (primary studies: 14; systematic reviews/meta-analyses: five; narrative reviews/expert opinion: 10). Risk-of-bias assessment revealed moderate-to-high overall risk: RCTs had small sample sizes (n = 12–42) and short follow-up (12–24 weeks), raising concerns about statistical power; observational studies were of fair-to-good quality (NOS 4–7 stars) but subject to confounding; and systematic reviews were of low-to-moderate confidence (AMSTAR-2). Primary evidence from RCTs and observational studies demonstrates that GLP-1 receptor agonists (GLP-1RAs)—particularly semaglutide and liraglutide—and the dual GIP/GLP-1 receptor agonist tirzepatide significantly increase total testosterone levels in men with obesity-related functional hypogonadism (mean increase 2.5–5.2 nmol/L). This effect is largely mediated by weight loss and improvement of insulin resistance rather than direct androgenic action. Evidence regarding whether baseline hypogonadism impairs glycemic or weight-loss response to incretin therapy is limited and indirect; no adequately powered comparative trials stratified by baseline testosterone status were identified. Conclusions: Incretin-based therapies, particularly GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide, appear to improve testosterone levels in men with obesity-related functional hypogonadism, an effect that is largely mediated by weight loss and improvement of insulin resistance rather than a direct androgenic action. However, direct comparative evidence between hypogonadal and eugonadal men regarding glycemic or weight-loss response to incretin therapy remains insufficient to draw firm conclusions. The hypothesis that male hypogonadism does not impair incretin therapy response is biologically plausible but is currently supported only by indirect evidence. Prospective, adequately powered trials stratified by baseline testosterone status are needed to resolve this question. Full article