Journal of Endocrinological Investigation最新文献

{"title":"Close relationship, similar phenotype of GATA4 and NR5A1 mutations: gonadal dysgenesis and puberty development.","authors":"Sema Nilay Abseyi, Zeynep Şıklar, Elif Özsu, Sirmen Kızılcan Çetin, Şafak Demirtaş, İlkyaz Türktan, Zehra Aycan, Merih Berberoğlu","doi":"10.1007/s40618-025-02684-4","DOIUrl":"https://doi.org/10.1007/s40618-025-02684-4","url":null,"abstract":"<p><strong>Introduction: </strong>Sex differentiation is a complex process controlled by several genes. GATA4 and NR5A1 interact at all stages of this process, starting from bipotential gonad development to testicular differentiation. Mutations in these two genes, which are in close relationship to each other in both Leydig and Sertoli cell development and function, may cause similar phenotypes. There have been reports in the literature of patients with the NR5A1 mutation becoming virilized at puberty, but no reports of GATA4 virilizing at puberty. We evaluated the characteristics of 46, XY gonadal dysgenesis patients with NR5A1 and GATA4 mutations, which we follow in our clinic to determine diagnostic clues.</p><p><strong>Results: </strong>We had ten 46, XY cases with NR5A1 and/or GATA4 mutations (10 from 8 different families). Clinical and hormonal features of all cases were compatible with gonadal dysgenesis. The phenotype was variable, such as ambiguous genitalia, amenorrhea, or pubertal virilization. Six out of 10 cases were raised as girls. A broad range of 46, XY DSD phenotypes, including isolated hypospadias, ambiguous external genitalia with a bifid scrotum, and/or micropenis up to fully female external genitalia, have been linked to GATA4 and NR5A1 variations. In our study, we have one case with a GATA4 mutation and two cases with NR5A1 mutation that became virilized at puberty.</p><p><strong>Conclusion: </strong>In cases of DSD, abnormal expression of the GATA4 gene should be considered even if there is no congenital heart disease (CHD). The NR5A1 and GATA4 gene mutations should be included in the differential diagnosis of DSD patients when virilization during puberty has been identified.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-database pharmacovigilance assessment of GLP-1 receptor agonist-related ophthalmic risks using advanced signal detection in FAERS and vigibase.","authors":"Xiao Cheng, Ziwei Jiang, Guangyao Li, Jiawei Wang, Furong Han","doi":"10.1007/s40618-025-02712-3","DOIUrl":"https://doi.org/10.1007/s40618-025-02712-3","url":null,"abstract":"<p><strong>Background: </strong>The expanding clinical use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and obesity has raised concerns about underrecognized ocular adverse events (AEs). Despite their metabolic benefits, fragmented evidence and methodological limitations in pharmacovigilance systems hinder comprehensive risk characterization. This study aimed to systematically evaluate ocular toxicity signals associated with GLP-1 RAs using advanced signal mining across the FDA Adverse Event Reporting System (FAERS) and VigiBase.</p><p><strong>Methods: </strong>Data from FAERS (2005-2025 Q1) and VigiBase (1987-2025 Q1) were analyzed for ocular AEs linked to five GLP-1 RAs (exenatide, liraglutide, dulaglutide, semaglutide, lixisenatide). Disproportionality analyses using Bayesian (Information Component, IC₀₂₅ > 0) and frequentist (Reporting Odds Ratio, ROR 95% CI > 1) methods identified significant signals. Duplicate reports and incomplete data were excluded, with statistical processing performed in R packages and Excel software.</p><p><strong>Results: </strong>Across both databases, ocular AEs predominantly occurred in individuals aged 45-64 and females. Semaglutide exhibited the strongest signals, notably for NAION (ROR = 40.18, IC₀₂₅ = 2.06 in VigiBase and ROR = 31.46, IC₀₂₅ = 4.84 in FAERS), with 2,878 cases in VigiBase and 2,047 in FAERS. Dulaglutide showed high rates of visual impairment and diabetic retinopathy. Early-onset AEs (≤ 30 days) were common with dulaglutide and semaglutide, while exenatide-related events peaked after > 360 days. Discrepancies between databases emerged, such as absent liraglutide/lixisenatide signals in VigiBase but moderate activity in FAERS. Furthermore, review of the prescribing information for these GLP-1RAs indicates that ocular adverse events are incompletely characterized. Diabetic retinopathy is reported solely for semaglutide and dulaglutide, while blurred vision is the only ocular event listed for lixisenatide. Other potential ocular risks are not mentioned in any of the respective drug labels.</p><p><strong>Conclusion: </strong>This large-scale pharmacovigilance analysis suggests underrecognized ocular safety signals associated with GLP-1 RAs, most prominently NAION with semaglutide and visual impairment/diabetic retinopathy with dulaglutide. The distinct AE profiles, temporal patterns (early vs. late onset), and database discrepancies highlight the complexity of GLP-1 RA ocular toxicity. These findings underscore the need for enhanced clinical vigilance, targeted post-marketing surveillance, and consideration of label updates to reflect these emerging ocular safety concerns.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrinological and clinical perspectives on the sella turcica - comment on Vaccarezza et al.","authors":"Halil Tekiner, Fahrettin Kelestimur","doi":"10.1007/s40618-025-02713-2","DOIUrl":"https://doi.org/10.1007/s40618-025-02713-2","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to the letter of Tekiner and Kelestimur.","authors":"Mauro Vaccarezza, Samanta Taurone, Mauro Palmieri, Francesco M Galassi, Luigi Cofone, Marco Artico, Veronica Papa","doi":"10.1007/s40618-025-02714-1","DOIUrl":"https://doi.org/10.1007/s40618-025-02714-1","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hazard and determinants of dropout and rehospitalization in patients with obesity after residential rehabilitation.","authors":"Daniele Sola, Samuele Minari, Raffaella Sabatino, Davide Soranna, Elisa Prina, Stefania Mai, Silvia Martinelli, Roberta Vietti, Raffaella Radin, Alessandra Rimella, Antonella Zambon, Massimo Scacchi","doi":"10.1007/s40618-025-02708-z","DOIUrl":"https://doi.org/10.1007/s40618-025-02708-z","url":null,"abstract":"<p><strong>Purpose: </strong>To identify clinical and sociodemographic factors that predict follow-up discontinuation and rehospitalisation after multidisciplinary residential rehabilitation for severe obesity, thereby defining high-risk patient profiles and guiding tailored retention strategies.</p><p><strong>Methods: </strong>We retrospectively followed 1,851 adults with obesity discharged from a multidisciplinary residential programme between 2015 and 2018 (median BMI 42 kg m⁻²). Dropout, defined as more than twelve months without contact, was studied with discrete-time survival models; time to rehospitalisation was analysed with Cox regression.</p><p><strong>Results: </strong>Within twelve months 1,513 patients (87%) discontinued follow-up. Each five-year increase in age lowered drop-out risk (HR 0.97, 95% CI 0.94-0.99, p = 0.004); diabetes had a similar protective effect (HR 0.89, 0.79-1.00, p = 0.0455). Rehospitalisation occurred in 591 patients (32%). Risk increased with age (5-years increment; HR = 1.05, 95% CI 1.01-1.09, p = 0.0191), baseline BMI (HR = 1.04, 95% CI 1.03-1.05, p < 0.0001), diabetes (HR = 1.22, 95% CI 1.02-1.30, p = 0.0306) and eating disorders (HR = 1.48, 95% CI 1.07-2.05, p = 0.0193).</p><p><strong>Discussion: </strong>Maintaining the benefits of residential rehabilitation is important. In our cohort, 87% of patients dropped out of follow-up within one year and 32% were readmitted. Two distinct profiles emerged: younger and non-diabetic subjects were prone to dropout, while patients with higher BMI, diabetes, or eating disorders were at higher risk of rehospitalization. Early identification of these groups may suggest flexible, technology-assisted follow-up for working-age patients and integrated metabolic-psychiatric care for complex cases, safeguarding outcomes and optimizing resources.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sperm DNA methylation landscape in infertile men with clinical varicocele: unravelling the treatment effect.","authors":"Deepshikha Arya, Delna Irani, Rahul Gajbhiye, Deepti Tandon, Priyank Kothari, Prakash Pawar, Dipty Singh","doi":"10.1007/s40618-025-02697-z","DOIUrl":"https://doi.org/10.1007/s40618-025-02697-z","url":null,"abstract":"<p><strong>Purpose: </strong>Varicocele has been associated with reduced male fertility potential. Treatment modalities for varicocele improve semen parameters, yet more than 50% of cases remain infertile. Varicocele-induced heat and hypoxia stress may cause aberrant epigenetic modifications, possibly leading to abnormal sperm functions. This study aims to investigate the genome-wide sperm DNA methylation alterations in infertile men with clinical varicocele and evaluate the effect of varicocele treatment on methylation and fertility status.</p><p><strong>Methods: </strong>This study includes 30 healthy fertile men and 50 infertile men with clinical varicocele. Whole genome bisulfite sequencing (WGBS) was employed to identify differentially methylated CpG (DMC) sites in sperm genomic DNA of the infertile men with varicocele compared to the fertile controls. DMCs located within genes associated with spermatogenesis and sperm functions were selected for validation in larger study population by pyrosequencing. Varicocele group were followed up after 3 months of either antioxidant treatment or varicocelectomy, and sperm DNA methylation changes were evaluated. Participants were monitored for 1 to 2 years following treatment to evaluate their fertility status.</p><p><strong>Results: </strong>From WGBS analysis, a total of 6414 DMCs and 1484 differentially methylated genes (DMGs) were identified. Signalling pathways involved in spermatogenesis process and sperm functions were enriched in the pathway analysis. Selected DMC within gene H2AX was significantly hypermethylated, and CDKN1B and BCR were hypomethylated in varicocele study population. However, after 3 months of varicocele treatment (both modes), notable restoration could only be observed in H2AX and CDKN1B DMCs. 20% of the follow-up patients achieved fertility after varicocele treatment and demonstrated a reversal of DNA methylation alterations.</p><p><strong>Conclusion: </strong>This study highlights the altered sperm DNA methylation landscape and its possible implications on altered spermatogenesis and sperm function in clinical varicocele cases. It also presents insights into the possibility of restoration of altered DNA methylation levels following varicocele treatment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the relationship between environmental air pollution exposure and abnormal gestational weight gain in twin pregnancies: a retrospective study.","authors":"Wei-Zhen Tang, Zhe-Ming Kang, Qin-Yu Cai, Hong-Yu Xu, Yi-Fan Zhao, Yi-Han Yang, Tai-Hang Liu, Fei Han, Yong-Heng Wang, Niya Zhou","doi":"10.1007/s40618-025-02691-5","DOIUrl":"https://doi.org/10.1007/s40618-025-02691-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gestational weight gain (GWG) is a critical indicator of the health and nutritional status of pregnant women and their fetuses. However, there is limited evidence on how air pollution affects abnormal GWG in twin pregnancies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this retrospective analysis of 3,598 twin pregnancies, participants were categorized into three groups based on GWG: optimal, inadequate, and excessive. We collected data on ambient air pollutants, including fine particulate matter (PM&lt;sub&gt;2.5&lt;/sub&gt;), inhalable particulate matter (PM&lt;sub&gt;10&lt;/sub&gt;), sulfur dioxide (SO&lt;sub&gt;2&lt;/sub&gt;), nitrogen dioxide (NO&lt;sub&gt;2&lt;/sub&gt;), carbon monoxide (CO), and ozone (O&lt;sub&gt;3&lt;/sub&gt;). Multivariable linear regression models examined the associations between air pollutant exposure in each trimester and GWG, analyzing pollutants both continuously and by quartiles. Logistic regression and trend analyses assessed the impact of these pollutants on the risks of inadequate and excessive GWG, adjusting for potential confounders. Restricted cubic spline (RCS) models visualized trimester-specific effects, and cumulative effects of extreme air pollution indices on GWG outcomes were evaluated using logistic regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The results indicated that exposure to PM&lt;sub&gt;2.5&lt;/sub&gt;, PM&lt;sub&gt;10&lt;/sub&gt;, SO&lt;sub&gt;2&lt;/sub&gt;, NO&lt;sub&gt;2&lt;/sub&gt;, and CO during pregnancy was positively associated with GWG in twin pregnancies, while O&lt;sub&gt;3&lt;/sub&gt; exposure was negatively associated. For inadequate GWG, PM&lt;sub&gt;2.5&lt;/sub&gt;, PM&lt;sub&gt;10&lt;/sub&gt;, and SO&lt;sub&gt;2&lt;/sub&gt; were identified as risk factors in the first trimester, with aORs of 1.008 (95% CI: 1.001-1.015), 1.006 (95% CI: 1.001-1.010), and 1.033 (95% CI: 1.000-1.067), respectively. In the second and third trimesters, these pollutants exhibited protective effects, alongside NO&lt;sub&gt;2&lt;/sub&gt; and CO. Conversely, O&lt;sub&gt;3&lt;/sub&gt; in the third trimester was a risk factor for inadequate GWG, with an aOR of 1.054 (95% CI: 1.008-1.102). Regarding excessive GWG, in the first trimester, PM&lt;sub&gt;2.5&lt;/sub&gt;, PM&lt;sub&gt;10&lt;/sub&gt;, SO&lt;sub&gt;2&lt;/sub&gt;, NO&lt;sub&gt;2&lt;/sub&gt;, and CO acted as protective factors, with aORs of 0.987 (95% CI: 0.980-0.994), 0.992 (95% CI: 0.986-0.997), 0.956 (95% CI: 0.924-0.989), 0.972 (95% CI: 0.948-0.997), and 0.243 (95% CI: 0.075-0.787), respectively. However, their effects reversed in the second and third trimesters, becoming risk factors for excessive GWG, with more pronounced effects observed in the third trimester. O&lt;sub&gt;3&lt;/sub&gt; remained a protective factor against excessive GWG in both the second and third trimesters, with aORs of 0.951 (95% CI: 0.905-0.999) and 0.876 (95% CI: 0.835-0.920), respectively. Finally, the effects of extreme air pollution exposure on GWG varied across different pregnancy stages. In the first trimester, extreme exposures to PM&lt;sub&gt;2.5&lt;/sub&gt;, PM&lt;sub&gt;10&lt;/sub&gt;, SO&lt;sub&gt;2&lt;/sub&gt;, and CO were associated with an increased risk of inadequate GWG, while NO&lt;sub&gt;2&lt;/sub&gt; exposure a","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gonadal and sexual function in men living with HIV: insights from a single-centre study.","authors":"Ilaria Bonaventura, Valeria Hasenmajer, Nicolò F D'Addario, Carlotta Pozza, Giancarlo Ceccarelli, Gabriella d'Ettorre, Claudio M Mastroianni, Emmanuele A Jannini, Daniele Gianfrilli","doi":"10.1007/s40618-025-02683-5","DOIUrl":"https://doi.org/10.1007/s40618-025-02683-5","url":null,"abstract":"<p><strong>Purpose: </strong>The study aimed to estimate the prevalence of hypogonadism and erectile dysfunction (ED) in male living with the human immunodeficiency virus (HIV), MLWH, and to explore associations between HIV-related variables and gonadal/sexual function.</p><p><strong>Methods: </strong>From 2019 to 2024, gonadal and sexual function were evaluated in consecutively enrolled MLWH through hormonal assessments and IIEF-15 questionnaire. Anthropometrics and HIV-related parameters, including type of Highly Active Anti-Retroviral Therapy, HAART, were also evaluated.</p><p><strong>Results: </strong>Among 60 MLWH, 70.0% presented with ED. Hypogonadism was observed in 18.3%, primarily hypogonadotropic (72.7%). Although both eu- and hypogonadal MLWH presented pathological IIEF-15 scores, no differences in the five domains of IIEF-15 were found. Hypogonadal MLWH had significantly higher BMI (p = 0.046) and greater smoking prevalence (p = 0.002), and lower 17β-estradiol levels (p = 0.017). In the whole cohort, total testosterone was negatively correlated to BMI (r=-0.595, p = 0.001) and waist circumference (r=-0.656, p = 0.011), and positively to 17β-estradiol (r = 0.457, p = 0.006) and SHBG (r = 0.325, p = 0.033). Calculated free testosterone also negatively correlated with BMI (r=-0.519, p = 0.023) and WC (r=-0.719, p = 0.019). Considering HAART, ED was more prevalent among those using Integrase Strand Transfer Inhibitor (p = 0.017). Conversely, MLWH treated with Proteinase Inhibitors showed higher total testosterone, SHBG and 17β-estradiol levels (respectively, p = 0.018, p = 0.015 and p = 0.020), despite no differences in calculated free testosterone or prevalence of ED.</p><p><strong>Conclusion: </strong>ED is highly prevalent multifactorial disorder in MLWH. Decreased serum testosterone levels, which are also related to increased visceral fat accumulation, are not the only driver of its onset. HIV-related factors, such as HAART, also appear to have an impact on gonadal and sexual function. A multidisciplinary approach, integrating infectious disease and sexual medicine expertise, is essential for optimal care.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between SGLT2 inhibitors and genital cancer: a meta-analysis and mendelian randomization study.","authors":"Bo Xu, Yilin Liu, Zunbo He, Jiecan Zhou","doi":"10.1007/s40618-025-02705-2","DOIUrl":"https://doi.org/10.1007/s40618-025-02705-2","url":null,"abstract":"<p><strong>Background: </strong>Effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on genital cancer risk remains unclear.</p><p><strong>Objective: </strong>The objective of this study was to investigate the impact of SGLT2 inhibitors/SGLT2 inhibition on genital cancer risk.</p><p><strong>Methods: </strong>We systematically searched PubMed, Web of Science, EU Clinical Trials Register, and ClinicalTrials.gov for large randomized controlled trials up to June 4, 2025. The Mantel-Haenszel method was applied, with risk ratios (RRs) and 95% confidence intervals (CIs) used for dichotomous outcomes. In the Mendelian randomization study, genetic variants in SLC5A2 served as instrumental variables to investigate the causal relationship between SGLT2 inhibition and genital cancers.</p><p><strong>Results: </strong>A total of 15 studies (16 trials) involving 101,430 patients were included. SGLT2 inhibitors did not significantly reduce genital cancer risk compared to placebo (RR 1.10; 95% CI 0.93-1.31; P = 0.28; moderate certainty of evidence), with consistent findings across subgroup analyses. No significant effects of SGLT2 inhibitors were observed for cervical, endometrial, ovarian, prostate, uterine, penile, or vulvar cancers. Dapagliflozin potentially increased the risk of male genital cancers (RR 1.31; 95% CI 0.99-1.74; P = 0.06). SGLT2 inhibition significantly reduced testicular [odds ratio (OR) 0.012; 95% CI 0.001-0.220; P = 0.003] and cervical (OR 0.013; 95% CI 0.001-0.122; P = 1.615 × 10 - 4) cancer risks. Pooled results from both discovery and replication cohorts demonstrated that SGLT2 inhibition reduced cervical cancer risk (OR 0.016; 95% CI 0.002-0.116; P < 0.0001).</p><p><strong>Conclusion: </strong>SGLT2 inhibitors exhibited a neutral overall risk profile for genital cancers, while genetic evidence demonstrated beneficial effects specifically for cervical cancer.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrinological complications of Duchenne muscular dystrophy and their subjective burden: observational study evaluating growth, puberty, and bone health.","authors":"Marie Rohlenova, Jana Haberlova, Petra Holotova, Marketa Kumhera, Lucie Simkova, Barbora Lauerova, Iveta Svabova, Ondrej Soucek","doi":"10.1007/s40618-025-02699-x","DOIUrl":"https://doi.org/10.1007/s40618-025-02699-x","url":null,"abstract":"<p><strong>Purpose: </strong>Duchenne muscular dystrophy (DMD) and its treatment by glucocorticoids are associated with secondary osteoporosis, short stature, and delayed puberty. We aimed at exploring the prevalence and subjective burden of these endocrinological complications after the implementation of recommended care protocols.</p><p><strong>Methods: </strong>A prospective cross-sectional medical report review of boys with DMD followed at the largest pediatric neuromuscular reference center. An online questionnaire survey was part of the study.</p><p><strong>Results: </strong>We included 35 boys with DMD, aged 5.7-19.7 years, most of them on long-term daily glucocorticoid therapy (91%). Vertebral fractures were present in 50% of boys, short stature in 74%, and pubertal delay in 56% of boys. The glucocorticoid treatment duration and cumulative doses were associated with a higher prevalence of short stature, but not with the presence of vertebral fractures or pubertal delay. Areal bone mineral density assessed by densitometry only poorly identified patients with osteoporosis, compared to clear evidence of vertebral fractures by lateral spine radiograph. The boys were most concerned about the risk of fractures. Those in the pubertal age, however, were troubled also by their childish looks. The boys tolerated the surveillance protocols and treatment of complications very well.</p><p><strong>Conclusions: </strong>Vertebral fractures, short stature, and delayed puberty are very frequent among glucocorticoid-treated boys with DMD. Lateral spine radiograph is a crucial means for bone health assessment, with an even larger yield than densitometry. A questionnaire survey identifies patient needs and improves complex health care.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}