Best practice & research. Clinical endocrinology & metabolism最新文献

{"title":"Cardiometabolic outcomes of early onset hypogonadism in males","authors":"Mariska Peck (Academic Foundation Programme Doctor) ,&nbsp;Paul Connelly (Consultant in Endocrinology) ,&nbsp;Angela K. Lucas-Herald (Senior Lecturer in Child Health, Honorary Consultant in Paediatric Endocrinology)","doi":"10.1016/j.beem.2025.102004","DOIUrl":"10.1016/j.beem.2025.102004","url":null,"abstract":"<div><div>Testosterone is an important vascular hormone, with multiple effects reported on the vasculature. As such, boys and men with early onset hypogonadism may have altered cardiovascular function, with the potential to result in adverse cardiometabolic outcomes in adulthood. Given the fact that cardiovascular changes in the young can affect future cardiovascular health, there is a need to better understand the influence of androgens on the vasculature in those with conditions such as 46, XY Disorders of Sex Development and Klinefelter Syndrome. This review summarises what is known about hypogonadism and the effects of testosterone supplementation in adults with hypogonadism, as well as what is currently understood in those with early onset hypogonadism specifically. A number of research gaps persist in this area and there is a need for international collaborative studies to address these for future generations of affected individuals.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102004"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The epidemiology of disorders of sex development","authors":"Agnethe Berglund ,&nbsp;Simon Chang ,&nbsp;Marie Lind-Holst ,&nbsp;Kirstine Stochholm ,&nbsp;Claus Højbjerg Gravholt","doi":"10.1016/j.beem.2025.102002","DOIUrl":"10.1016/j.beem.2025.102002","url":null,"abstract":"<div><div>During recent years the epidemiology of disorders of sex development (DSD) has been more clearly delineated. Here, we provide a detailed and up-to-date synopsis of the epidemiology of DSD, incorporating the latest body of knowledge in the field for sex chromosome DSD (Turner, Klinefelter, 47,XXX, and 47,XXY syndrome, and 45,X/46,XY mosaicism) as well as for 46,XX DSD and 46,XY DSD focusing on females with congenital adrenal hyperplasia (CAH), males with 46,XX DSD, females with Mayer-Rokitansky-Küster-Hauser syndrome and females with 46,XY DSD. Despite not fitting directly within the Chicago Consensus classification for DSD, we also include the few epidemiological studies addressing ambiguous genitalia. We show that epidemiological studies have improved our understanding of DSD and led to sound estimates of prevalence, have detailed morbidity and mortality patterns and have for some conditions also shed light on the impact on socioeconomic achievements.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102002"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences & disorders of sex development: A focus on outcomes","authors":"S. Faisal Ahmed ,&nbsp;Olaf Hiort","doi":"10.1016/j.beem.2025.102029","DOIUrl":"10.1016/j.beem.2025.102029","url":null,"abstract":"","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102029"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining sex in the sporting world","authors":"David J. Handelsman ,&nbsp;Stéphane Bermon","doi":"10.1016/j.beem.2025.102005","DOIUrl":"10.1016/j.beem.2025.102005","url":null,"abstract":"<div><div>At an elite international level, professional sports have a well-established fairness-based binary sex classification which is challenged by male-bodied athletes with female gender identity, notably male-to-female transgender and XY Disorders of Sex Development (DSD) individuals seeking to compete in female events. For sports where success depends on power and/or endurance, physical advantages stemming from male puberty, which produces men’s circulating testosterone concentrations 20–30 times those of children or women at any age, leading to larger and stronger muscles, bones, cardiorespiratory functions and blood hemoglobin. Yet complete suppression of endogenous testosterone after male puberty leaves a legacy of reduced but not eliminated physical advantages. Hence a protected female category in power sports is essential to allow women a fair and safe chance at the fame and fortune derived from success. For community, recreational and youth sports, or those without male physical advantages invoking safety or fairness issues, inclusivity may prevail.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102005"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of patient-centered outcomes in young children with differences of sex development","authors":"Salma R. Ali PhD ,&nbsp;Xanthippi Tseretopoulou MD ,&nbsp;David E. Sandberg PhD","doi":"10.1016/j.beem.2025.102030","DOIUrl":"10.1016/j.beem.2025.102030","url":null,"abstract":"<div><div>Patient-reported outcome measures (PROMs) are key to evaluating the real-life impact of care, particularly for individuals with differences/disorders of sex development (DSD). DSDs are congenital and life-long conditions, most often ascertained in infancy or adolescence, and are characterized by atypical chromosomal, gonadal, or phenotypic sex. PROMs capture vital aspects of health-related quality of life (HRQoL) and psychosocial well-being from the perspective of patients and caregivers, complementing traditional clinical outcomes. Despite their importance, there is a paucity of validated, DSD-specific PRO measures available across the lifespan, resulting in challenges for standardized assessment and clinical benchmarking. Recent developments have led to the creation and validation of shortened, condition-specific HRQoL questionnaires for young children with DSD and their parents, which demonstrate strong psychometric properties and good clinical acceptability. Integrating regular assessments with these PROMs, especially those tailored for DSD, into routine care and rare disease registries can support ongoing monitoring, facilitate timely psychosocial interventions, and enable robust evaluation of intervention effectiveness. However, several barriers to implementation remain, including respondent burden, variability in comprehension, cultural sensitivity, and the need for specialized personnel to interpret results and translate them into practical recommendations. Stigma associated with DSD can further hinder engagement, potentially resulting in under identification of those most in need. Future strategies should focus on the use of validated, culturally adapted PROMs across all age ranges, regular assessment intervals, and electronic integration within health records and registries. Incorporating PROMs enable a holistic, patient-centered approach to care for individuals with DSD, supporting improved outcomes and better informed shared decision making.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102030"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gonadectomy in individuals with a difference of sex development – For whom, when, why, and why not?","authors":"Sabine E. Hannema (Consultant Paediatric Endocrinologist) ,&nbsp;Michele A. O’Connell (Consultant Paediatric Endocrinologist)","doi":"10.1016/j.beem.2025.102019","DOIUrl":"10.1016/j.beem.2025.102019","url":null,"abstract":"<div><div>Several forms of differences of sex development (DSD) are associated with an increased risk of gonadal germ cell cancer, which can be prevented by a gonadectomy. However, when considering prophylactic gonadectomy potential benefits need to be carefully weighed against potential harms, taking into account factors such as endocrine function of the gonad, potential fertility and the risk of germ cell cancer. While evidence is available for particular diagnoses, to assess gonadal function and risk at an individual level remains challenging. A comprehensive approach to assessment is described. Alternatives to gonadectomy include surveillance for cancer development but current methods have low sensitivity and specificity. Undesired sex steroid production can be suppressed with GnRH analogue treatment. Unless it poses an unacceptable medical risk, it is generally preferable to delay a decision regarding gonadectomy until the individual can be involved in a shared decision making process.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102019"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormone replacement in disorders of sex development, and long-term effects","authors":"Anna Nordenström ,&nbsp;Alessandra Mangone ,&nbsp;Giovanna Mantovani","doi":"10.1016/j.beem.2025.102022","DOIUrl":"10.1016/j.beem.2025.102022","url":null,"abstract":"<div><div>Disorders of sex development, DSD, are in the majority of cases caused by alterations in the gonadal or adrenal function that affect steroid hormone synthesis or action. Gonadal deficiencies result in a need for testosterone or estradiol replacement to achieve pubertal development as well as for continuous life-long replacement with sex hormones. In cases with adrenal enzyme deficiencies, glucocorticoid and sometimes mineralocorticoid replacement may be required to normalize the hormonal situation. Long-term outcomes related to growth, bone mineral density, cardiovascular and metabolic health, as well as psychosocial wellbeing, are increasingly being reported, both in relation to different treatment strategies and as a consequence of insufficient or absent treatment. Transition from pediatric to adult care is a vulnerable period which needs to be organized and individually tailored to ensure lifelong treatment and optimized general health. Individuals with a DSD should be seen by multidisciplinary teams at all ages, for diagnostic evaluation, for treatment and for long-term clinical follow-up.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102022"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The options for delayed surgery – Is there evidence available for delayed genitoplasty in differences/disorders of sex development?","authors":"Hedvig Engberg ,&nbsp;Lisa Örtqvist ,&nbsp;Gundela Holmdahl","doi":"10.1016/j.beem.2025.102024","DOIUrl":"10.1016/j.beem.2025.102024","url":null,"abstract":"<div><div>The question whether delaying genital surgery in individuals with differences/disorders of sex development is an option, or an even better option than early surgery, is complex and based on many considerations. The evidence must be considered poor for both alternatives. This review aims to evaluate some important outcome studies from the last two decades regarding the potential benefits of delayed genital surgery and explores the feasibility of performing male and female genitoplasty after the onset of puberty.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102024"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Broader impact and outcome of human NR5A1/SF1 variants","authors":"Chrysanthi Kouri (Endocrinology and Genetics Researcher) ,&nbsp;Rawda Naamneh-Elzenaty (Biomedical Researcher) ,&nbsp;Idoia Martinez de Lapiscina (Endocrinology and Genetics Researcher) ,&nbsp;Christa E. Flück (Pediatric Endocrinologist)","doi":"10.1016/j.beem.2025.102023","DOIUrl":"10.1016/j.beem.2025.102023","url":null,"abstract":"<div><div>Nuclear Receptor Subfamily 5 Group A Member 1, also known as Steroidogenic Factor 1 (<em>NR5A1</em>/SF-1), plays a crucial role in human sex development and steroidogenesis. Pathogenic variants in the NR5A1 gene are well-established causes of 46,XY and 46,XX differences in sex development (DSD) and primary ovarian insufficiency. While numerous studies have demonstrated that these variants impair puberty and fertility, the full spectrum of pubertal and reproductive effects in affected individuals remains difficult to define. Emerging evidence suggests broader, long-term implications beyond gonadal function, including effects on spleen function and metabolic health, not only in individuals with DSD, but also in asymptomatic carriers of <em>NR5A1</em>/SF-1 variants within the general population. However, these findings require validation through larger, longitudinal studies. This review provides a comprehensive overview of current knowledge and existing gaps, emphasizing the broader impact and long-term effects of <em>NR5A1</em>/SF-1 variants.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102023"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen insensitivity and the evolving genetic heterogeneity","authors":"Nadine Hornig ,&nbsp;Rafael Loch Batista","doi":"10.1016/j.beem.2025.102000","DOIUrl":"10.1016/j.beem.2025.102000","url":null,"abstract":"<div><div>Androgen Insensitivity Syndrome (AIS) is a 46,XY difference of sex development (DSD) classically caused by mutations in the androgen receptor (<em>AR</em>) gene, leading to variable androgen resistance and a broad phenotypic spectrum traditionally classified as complete, partial, or mild. Phenotypic variability can occur even with identical <em>AR</em> mutations, particularly those within the ligand-binding domain of the AR. Emerging evidence implicates non-coding regulatory variants, deep intronic mutations, AR co-regulator dysfunction, and oligogenic inheritance in the aetiology of AIS. The molecular diagnostic workflow should incorporate either targeted <em>AR</em> sequencing or whole-exome sequencing, depending on the clinical context. Biochemical and functional assays remain clinically useful, especially when <em>AR</em> variants are not detected or when variants of unknown significance (VUS) are identified. Advances in patient-derived hiPSC models and testicular organoids provide new insights into AR function and therapeutic strategies. Expanding genomic and epigenetic research will refine diagnostic accuracy, and personalized care, ultimately optimizing patient outcomes in AIS.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 4","pages":"Article 102000"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}