In their recent article, Oosthoek et al. propose a paradigm shift in the evaluation and justification of gender-affirming medical treatment (GAMT) for minors with gender dysphoria or gender incongruence. Rather than relying on traditional clinical outcome measures such as mental health, global functioning, or quality of life, they argue for a patient-defined standard centered around "embodiment goals" and autonomy. While we acknowledge the importance of incorporating patient perspectives and values, we raise significant theoretical and clinical concerns about the implications of this approach. Central to our critique is the tension between the authors' framework and established principles of medical ethics, especially beneficence and non-maleficence. We argue that abandoning the expectation of demonstrable clinical improvement undermines the professional ethos of health care and poses risks to vulnerable adolescents. Moreover, we caution against using ethics as a rhetorical refuge to justify treatments for which evidence of benefit remains weak or inconsistent. Instead of redefining effectiveness post hoc, we advocate for a robust evidence-based framework that prioritizes well-being and supports careful, honest shared decision-making. Non-medical interventions, including psychosocial support and treatment of comorbidities, should remain the first-line approach until stronger evidence for GAMT emerges. We call for improved research that evaluates both medical and non-medical interventions using established clinical outcome measures.

Gender dysphoria (GD) can be defined as a persistent and intense experience of incongruence between biological sex and perceived gender identity, accompanied by significant distress and, frequently, an explicit desire to modify bodily characteristics. In the current scientific context, the study of GD is structured around several lines of research, including the possible existence of neurobiological differences between cisgender children/pre-adolescents (controls) and transgender individuals, alterations in the networks involved in body self-perception, and the potential contribution of biological factors - including genetic components - to the development of transsexuality, as has been demonstrated in some adult trans individuals, as well as to gender identity more broadly. In the clinical domain, interventions aimed at children and pre-adolescents with GD - primarily based on the administration of puberty blockers, followed in some cases by cross-sex hormone therapies and, exceptionally, surgical interventions - raise specific questions that go beyond those already identified in adult populations. These issues are particularly related to the role played by sex hormones in brain development during critical stages of neurodevelopment, as well as to the potential long-term effects on endocrine systems and reproductive function. The analysis of the available evidence on side effects, together with consideration of their potentially irreversible nature in certain cases, highlights the need for especially rigorous ethical evaluation. In this regard, the principle of primum non nocere assumes central importance, given that significant uncertainties remain as to whether the potential benefits of these interventions outweigh their inherent risks. Likewise, it is essential to ensure an interpretation of scientific data free from ideological bias, as well as to reinforce the requirement for a comprehensive diagnostic approach encompassing endocrinological, psychological, and social dimensions. This is further compounded by the critical issue of the validity of informed consent in minors, particularly in relation to their level of maturity. Finally, recent advances in the study of genetic bases and in the understanding of the neural networks involved in bodily self-perception open up the possibility of new therapeutic approaches, the exploration of which requires deeper and more systematic scientific development.

Transgender and gender-diverse (TGD) patients with cancer face unique and intersecting challenges related to fertility preservation. Although professional societies recommend early fertility counseling for both patients with cancer and individuals undergoing gender-affirming treatment, evidence specifically addressing oncofertility in TGD populations remains limited. Gender-affirming hormone therapy may affect gonadal function and gametogenesis, while interruption of hormone therapy for fertility preservation may exacerbate gender dysphoria. Fertility preservation options include oocyte, embryo, sperm, ovarian tissue, and testicular tissue cryopreservation, with selection dependent on reproductive anatomy, pubertal status, prior treatment, and oncologic considerations. TGD patients also face substantial barriers to fertility preservation, including cost, inadequate counseling, insufficient provider expertise, discrimination or bias, and lack of access to fertility care. This narrative review examines current evidence regarding fertility and fertility preservation in TGD patients, with particular attention to patients with cancer, and identifies critical gaps in counseling, clinical practice, research, and policy. Improving care will require early and individualized counseling, multidisciplinary collaboration, equitable access to these services, longitudinal research addressing reproductive outcomes in TGD cancer survivors, and the creation of inclusive clinical environments that support patients throughout fertility preservation and cancer care.

In youth-i.e., adolescents and young adults-mental disorders represent a major burden on well-being and quality of life. This scientometric study aimed to map research trends concerning any mental disorder in youth. We searched the Web of Science Core Collection for studies published between 01/01/1985 and 28/08/2025, using keywords on mental disorders and youth. Co-citation reference networks were extracted. R-bibliometrix/CiteSpace were used. 65,684 studies were included, forming a well-structured co-reference network. A trend in the 1980s concerned the prevalence/outcomes of specific mental disorders such as depressive and anxiety disorders. In the 1990s/2000s, research trends concerned assessment tools, pharmacotherapy (e.g., antidepressants, antipsychotics), bipolar disorders and schizophrenia. In the 2010s, early intervention for psychosis was a dominant focus, influencing prevention in mental health. The 2010s also focused on ADHD, eating disorders, gaming disorder, autism, depression and suicide, fMRI, and transgender health, beyond gender dysphoria. In the 2020s, a recent trend has increasingly focused on global evidence on the age at onset and burden across mental disorders, access to care, network analysis, and COVID-19. Over time, research has broadened the focus from adolescence to youth across mental health problems. Both disorder-specific and transdiagnostic research trends were observed. Novel trends in 2023-2025 included substance use, lifestyle psychiatry, evidence synthesis and non-suicidal self-injury. Most studies were conducted in Western countries. Underrepresented research areas included the involvement of youth with lived/living experience in identifying meaningful outcomes, open science, implementation research, economic evaluations, machine-learning approaches, and social determinants of mental health.

Transgender and gender diverse (TGD) individuals represent a growing population with specific cardiovascular health needs. Current cardiovascular prevention strategies are largely derived from cisgender populations and may not adequately account for the combined effects of gender-affirming hormone therapy (GAHT) and other determinants. This expert opinion summarizes current evidence regarding cardiovascular health in TGD individuals, focusing on the cardiovascular effects of GAHT, population-specific cardiovascular risk factors, practical approaches to cardiovascular risk assessment, and future research priorities. Available evidence indicates that GAHT is associated with changes in cardiometabolic risk factors, haemostasis, vascular function, and cardiac physiology. Feminizing GAHT is associated with an increased risk of venous thromboembolism, whereas masculinizing GAHT is associated with adverse lipid changes, erythrocytosis, and a potentially increased risk of major cardiovascular events. However, causal inference is limited by the predominance of observational studies, relatively young study populations, heterogeneous GAHT regimens, short follow-up, and the absence of randomized study evidence. Population-level cardiovascular disparities in TGD should not be attributed to GAHT alone and smoking, obesity, physical inactivity, minority stress, socioeconomic disadvantage, and unequal access to healthcare may independently or interactively influence cardiovascular risk. Current cardiovascular risk prediction tools have not been validated or calibrated in TGD populations and do not account for GAHT exposure or TGD-specific psychosocial and structural determinants. Cardiovascular risk assessment in TGD individuals should integrate conventional risk factors, transgender-related cardiovascular risk factors, and patient involvement regarding individual goals. A coordinated multidisciplinary approach may facilitate personalized cardiovascular prevention while supporting access to gender-affirming care. Future research should prioritize long-term prospective studies and development of risk prediction models tailored to TGD populations.

Individuals discharged from specialist gender identity services continue to require coordinated hormonal, medical, and psychosocial care. Despite this, there are limited standardised pathways for the transition of care from specialist clinics to ongoing primary care settings. This was developed by a multidisciplinary team including endocrinologists, specialist gender clinicians, reproductive medicine specialists and general practice. It draws on existing service specifications and shared-care protocols. The position statement emphasises the need for clear documentation at discharge from the gender identity clinic, including the hormone regimen, monitoring schedule, and risk stratification. It advocates a collaborative approach between specialist gender clinics and primary care providers. It also highlights the importance of patient education and empowerment for lifelong monitoring needs, lifestyle risk mitigation, such as smoking cessation, weight management, cardiovascular health, as well as contraception and fertility considerations. It provides guidance on when to seek specialist referral for hormonal management, and to adopt a multidisciplinary approach once complications or changes arise. This position statement supports minimal effective hormone dosing when appropriate, and the adoption of pragmatic strategies in later life or palliative contexts. A coordinated, patient-centred approach is key to optimizing long-term outcomes and ensuring safe, effective continuation of gender-affirming care.

Existing reviews of mental health outcomes among trans and gender diverse (trans)people have been limited by incomplete coverage, restricted or selected samples, afocus on youth populations, and insufficient exploration of heterogeneity. We aimed togenerate pooled prevalence estimates, and examine variation in mental disorders,suicidality, and non-suicidal selfinjury (NSSI) among trans adults globally. Weconducted a systematic review and meta-analysis of studies reporting current orlifetime prevalence of mental disorders, assessed using symptom screeninginstruments with validated general-population thresholds or clinical diagnoses,alongside self-reported suicidality and NSSI. MEDLINE, Embase, and PsycINFO weresearched from January 1, 1990-April 7, 2026. Restricted or highly selectedsubpopulations were excluded, except for gender-affirming clinic samples. Estimateswere calculated overall and by gender identity. Subgroup/meta-regression analysesexamined variation by study and sociodemographic characteristics. We identified 207studies with 134,071 trans participants across 52 countries. Pooled prevalenceestimates, combining symptoms exceeding screening thresholds and clinicallydiagnosed disorders, were 40.1% (95% CI 35.6-44.8) for depression, 29.8% (20.3-40.2) for anxiety, and 23.6% (14.9-33.5) for post-traumatic stress disorder. Past-12-month prevalence was 43.1% (38.9-47.3) for suicidal ideation, 9.3%(7.7-11.0) forsuicide attempts, and 26.1% (20.4-32.2) for NSSI. Limited data suggested higherprevalences among non-binary participants. Prevalence estimates varied significantlyby assessment method, recruitment setting, and geographic region. Trans peopleexperience a substantial burden of mental disorders, suicidality, and NSSI. Elevatedprevalence relative to general population comparator estimates indicates a need for affirming, accessible mental healthcare and improved approaches to assessing andinterpreting mental health outcomes in trans populations.

Masculinizing hormone therapy (MHT) is used in individuals with gender dysphoria to promote the development of secondary sexual characteristics. Testosterone is classified as probably not porphyrinogenic for acute porphyrias (AP) and is used to suppress the menstrual cycle and reduce ovarian estrogen production under medical supervision. Women with AP may experience symptoms related to the menstrual cycle, including acute attacks. MHT is a chronic therapy that presents a particular challenge in AP because synthetic testosterone is metabolized by CYP3A4, potentially affecting the hepatic heme pool. Our aim was to evaluate longitudinal changes in heme pathway parameters in a patient undergoing MHT to monitor clinical and biochemical evidence of acute intermittent porphyria (AIP) activation. A 27-year-old patient with latent AIP, assigned female at birth and carrying the p.Gly111Arg variant, began MHT with daily Androlone gel (1% testosterone) in 2021. The patient developed masculinizing features and became amenorrheic in August 2022. Testosterone levels were adjusted to the desired range (3-7 ng/mL). General biochemical and metabolic parameters remained within normal ranges. The patient reported a marked sense of well-being and no adverse effects. Heme precursors and porphyrin excretion remained close to reference values: 5-aminolevulic acid: 1.3-2.5 mg/24 h (RV:≤4 mg/24 h); porphobilinogen: 1.0-2.9 mg/24 h (RV: ≤2 mg/24 h); total urinary porphyrins: 31-213 μg/24 h (RV:≤250 μg/24 h). This is the first reported case of MHT in a patient with AIP in Argentina. These findings suggest that MHT may be feasible in patients with latent AIP, provided that close biochemical and clinical monitoring is maintained.

Transgender, nonbinary, and gender diverse (TGD) individuals experience stressors and risk factors related to disordered eating that are unique from cisgender counterparts. To account for these factors in symptom measurement, three studies were completed to develop and validate a new, community-specific scale for use with TGD adults. A total of 908 community-based TGD adults with a variety of intersecting identities completed surveys across three studies to test an initial pool of items, establish and validate the scale's factor structure, and assess the scale's convergent and predictive validity and test-retest reliability. Exploratory factor analyses resulted in a four-factor solution that accounted for 70.06% of variance. Confirmatory factor analyses supported a second-order hierarchical model with four latent factors that load onto a general "Gender Related Disordered Eating" factor, χ2(86)=249.81 (p < .001), RMSEA = 0.09, SRMR = 0.07, NFI = .90, CFI = .92. The final scale includes 18 items, including three clinical indicator items that differentiate body dissatisfaction associated with weight versus gender dysphoria. The scale showed strong convergent, predictive, and incremental validity and test-retest reliability. The measure appears to perform well with community-based TGD adults and offers unique insight into the factors underlying disordered eating among TGD individuals. With further validation and development, this scale may improve measurement in both clinical and research settings.

Cervical cancer is a preventable cancer through the use of screening and the human papillomavirus (HPV) vaccine. Even with the availability of screening and the HPV vaccine, disparities exist by geographic area (rural versus urban) and sexual orientation and gender identity. Due to stigma the lesbian, gay, bisexual, transgender, queer, and other sexual and gender minorities (LGBTQ+) encounter in healthcare, they are less likely to engage in routine healthcare. This is compounded in the rural LGBTQ+ population because of additional barriers such as lack of access to care, lack of competent providers, and financial constraints. A recent study in LGBTQ+ individuals in rural central and Southern Illinois revealed that only 50% of individuals were compliant with cervical cancer screening. Barriers to screening included poor prior experiences, financial burden, and gender dysphoria. There are strategies that could be utilized to address the disparities that exist among rural LGBTQ+ individuals. These include enhancing medical and clinical education, enhancing workforce diversity, enhancing the clinical environment to promote health equity, and enhancing regulatory pressure to enhance LGBTQ+-specific education opportunities. These efforts will be critical in reducing the health disparities that exist in cervical cancer screening among the LGBTQ+ population.