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PubMed2026

The role of the external genitalia score (EGS) in evaluation of disorders of sex development.

OBJECTIVE: To investigate the utility of the External Genitalia Score (EGS) in the diagnosis of disorders of sex development (DSD) and decision-making regarding gender assignment in affected patients. METHODS: A retrospective cohort study was conducted, enrolling 114 DSD patients aged <2 years (88 reared as males, 26 reared as females) treated at our hospital between April 2005 and June 2023, alongside 40 hypospadias patients aged <2 years who underwent surgery at our institution from January to July 2023. Demographic data (age) and EGS assessments of external genitalia were collected for all participants. Statistical analyses included independent samples t-tests, Mann-Whitney U tests and Receiver Operating Characteristic (ROC) curve analysis. Specifically, EGS scores were compared between the hypospadias group and the male-reared subgroup of the DSD cohort; additionally, EGS scores were contrasted between male-reared and female-reared DSD subgroups. RESULTS: The mean age was 20.3 months in the hypospadias group, 17.9 months in the male-reared DSD group, and 18.8 months in the female-reared DSD group. EGS ranged from 5.5 to 11.5 (median 10.5) in the hypospadias group and from 1 to 12 (median 4.75) in the DSD group. ROC curve analysis was performed to compare EGS scores between the hypospadias group and the male-reared DSD subgroup. The optimal diagnostic threshold was determined by maximizing the Youden index (sensitivity + specificity - 1), which balances sensitivity and specificity. A cut-off value of ≤8.50 was identified as indicative of DSD; clinically, patients with an EGS score <9 should be prioritized for DSD screening. Further comparison between male-reared and female-reared DSD subgroups yielded a threshold of 4.00. Clinically, an EGS score ≤4 may suggest a preference for female gender assignment. DISCUSSION: The EGS scale is a reliable, valid, and clinically feasible tool for characterizing external genitalia in DSD patients. An EGS score of 9 can serve as an indicator for initiating detailed sex development evaluation in hypospadias patients. While gender assignment in DSD is a complex, multifactorial process, EGS scores showed a significant association with the sex of rearing in our cohort. In settings where major determinants are balanced, EGS may serve as an adjunctive descriptive parameter rather than a standalone decision-making tool.

Humans↗

PubMed1975

Long-term steroid therapy in patients with adrenogenital syndrome.

Fifteen years' experience with the adrenogenital syndrome at Duke University Medical Center is reviewed. Twenty-six patients were diagnosed before age 2. Of these, 20 had the salt-losing syndrome. The complications encountered and the results obtained in terms of growth, developemnt, and fertility are discussed. Delay in diagnosis and inappropriate gender assignment continue to be a problem.

17-Ketosteroids↗

PubMed2026

Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

Humans↗

PubMed2026

Reproductive Intentions and Fertility Preservation Among Transgender and Nonbinary Individuals: A Cross-Sectional Study in Brazil.

PURPOSE: This study evaluated reproductive intentions, fertility-related knowledge, prior fertility counseling, and factors associated with reproductive intentions among transgender and nonbinary individuals receiving care at a Brazilian public reference center. METHODS: This cross-sectional study with a qualitative component was conducted between July and November 2025 in a specialized gender-affirming care clinic in Brazil. Quantitative data included sociodemographic characteristics, reproductive history, gender-affirming hormone therapy (GAHT), and fertility-related variables. Logistic regression was used to assess factors associated with desire for future parenthood. Responses to a single open-ended question regarding perceived effects of GAHT on fertility were analyzed using thematic content analysis. RESULTS: Eighty-two participants were included (mean age 27.5 ± 7.4 years). Most identified as transgender men (65.9%), followed by transgender women (26.8%) and nonbinary individuals (7.3%); 79.3% were receiving GAHT. Although 63.4% expressed a desire for future parenthood, only 7.3% had children. Current interest in fertility preservation was reported by 20.8% (15/72). Having children (adjusted odds ratio [aOR] = 0.03; 95% confidence interval [CI]: 0.001-0.62; p = 0.023) and each additional year of GAHT duration (aOR = 0.83; 95% CI: 0.70-0.99; p = 0.038) were associated with lower odds of desiring future parenthood. Sex assigned at birth was not independently associated with reproductive intentions. Qualitative analysis revealed misconceptions, uncertainty, and conditional beliefs regarding fertility. CONCLUSIONS: Desire for future parenthood was common among transgender and nonbinary individuals, whereas engagement with fertility preservation remained limited. These findings highlight the need for longitudinal, patient-centered reproductive counseling integrated into gender-affirming care.

fertility preservation↗

PubMed2026

Open Dialogue versus treatment as usual for adults presenting in crisis to mental health services in England (the ODDESSI Trial): a multisite cluster-randomised trial.

BACKGROUND: Open Dialogue is a person-centred, transdiagnostic model of mental health care that emphasises continuity, therapeutic relationships, and collaboration with the service user's social network. Open Dialogue is a service-wide approach to care involving network meetings with the service user, members of their social network, and usually two practitioners who support the network throughout the duration of care. In this cluster-randomised trial, we aimed to evaluate the clinical effectiveness of Open Dialogue versus treatment as usual for adults presenting in crisis to community mental health services in England. METHODS: This multicentre, parallel two-arm, cluster-randomised, controlled superiority trial was conducted in mental health services in five National Health Service trusts in London and the South of England. Clusters were defined at the level of primary care practices within service catchment areas. Participants were adults aged 18 years or older presenting in crisis to mental health services and registered with a practice within trial clusters. Randomisation was done at the cluster level (1:1), stratified by catchment area, and balanced on average general practice (GP) list size and Index of Multiple Deprivation (2015). The chief investigator, senior statistician, and assessors of the primary outcome were masked in the study. Participants either received Open Dialogue or treatment as usual, which refers to the functional team model currently implemented throughout English mental health services. The primary outcome was time (days) to first relapse following initial recovery from the index crisis censored at the end of the 2-year follow-up period. Participant-reported secondary outcomes were EuroQol Visual Analogue Scale, Social Provisions Scale, Lubben Social Network Scale, Questionnaire about the Process of Recovery, and the Client Satisfaction Questionnaire, measured at five timepoints over 2 years, and clinical measures were extracted from electronic health records. People with relevant lived experience were involved in the design and execution of the study. Fidelity to the model of care in Open Dialogue and treatment as usual, and adherence to the delivery of Open Dialogue, were measured prior to each site starting participant recruitment, then every 6 months thereafter until the final participant follow-up in that site. The trial was retrospectively registered (ISRCTN52653325) and is complete. FINDINGS: 185 general practices associated with six mental health Trusts across England were identified for screening. 105 practices were excluded, and 80 were included in cluster formation, forming 32 clusters that were randomly assigned (16 to treatment as usual and 16 to the Open Dialogue intervention). One mental health trust (two clusters) withdrew, resulting in five mental health trusts (30 clusters) participating in the trial. Between June 25, 2019, and Dec 9, 2021, 494 participants (266 [54%] female gender, 221 [45%] male gender, 341 [69%] White British) with a mean age of 38·1 years (SD 13·4) provided consent for study inclusion (223 in the treatment as usual group and 271 in the Open Dialogue group). Of these, 174 (78%) in the treatment as usual group and 225 (83%) in the Open Dialogue group recovered and had data enabling relapse determination; there was no significant difference between groups on the primary outcome of time to relapse following initial recovery (marginal hazard ratio 0·95 [95% CI 0·67-1·32]). For secondary outcomes, Open Dialogue was associated with significantly lower probabilities of psychiatric inpatient admission and re-referral to crisis care or secondary mental health services, and with improvements in self-rated recovery, health-related quality of life, and satisfaction with services. There were no significant differences in social network quality or size. There were 386 serious adverse events (281 in the treatment as usual group and 105 in the Open Dialogue group); 376 (97%) were deemed to be unrelated to the intervention. INTERPRETATION: Open Dialogue did not reduce time to first relapse compared with treatment as usual, the primary outcome, but it reduced acute inpatient bed use, improved service user reported outcomes and experience, and there were no significant safety concerns. Further investigation is required to determine whether Open Dialogue can enhance the effectiveness and acceptability of crisis care and continuing care in community mental health services. FUNDING: National Institute for Health Research.

Humans↗

PubMed2026

Brief Report: Beyond Testing: Exploring the Psychosocial Impact of HIV Self-Testing Among Ugandan Gender-Diverse Sex Workers.

BACKGROUND: The psychosocial effect of HIV self-testing (HIVST) on sex workers' self-esteem, depression, alcohol misuse, perceived sex work stigma, and empowerment remains poorly characterized. We hypothesized that HIVST would reduce sex work stigma and improve these psychosocial outcomes by enabling private, autonomous testing and reducing exposure to stigmatizing healthcare encounters. SETTING: Kampala, Uganda. METHODS: We conducted a secondary analysis of the Empower study (NCT03426670), an open-label randomized trial in which 117 cisgender female, transgender female, and cisgender male sex workers were assigned 1:1 to monthly HIVST plus quarterly clinic-based testing, or to quarterly clinic-based testing alone, and followed for 12 months. Self-esteem (Rosenberg Self-Esteem Scale), depressive symptoms (PHQ-2), alcohol misuse (RAPS4), perceived sex work stigma (adapted Female Sex Worker Stigma Scale), and empowerment were assessed quarterly. Mixed-effects regression models, adjusted for baseline values, evaluated intervention effects. RESULTS: Data from 117 participants were analyzed, including 7 early disenrollments. Over 12 months, HIVST participants reported significantly lower perceived sex work stigma than standard of care participants (β = -0.38, P = 0.04; monthly reduction P = 0.003), although the rate of decline did not differ significantly between arms (interaction P = 0.08). Self-esteem and depressive symptoms improved in both arms, with no between-arm differences (interaction P = 0.41 and 0.32). Alcohol misuse and empowerment showed no significant arm differences. CONCLUSION: HIVST may reduce sex work stigma without adverse psychosocial effects, supporting its integration into combination HIV prevention for gender-diverse sex workers in sub-Saharan Africa.

Humans↗

PubMed2026

Healing from within: A randomized controlled trial of a novel expressive writing intervention among trans and gender expansive adults.

Transgender and gender expansive (TGE) populations in the United States experience high rates of mental health disparities. High rates of depressive and anxiety symptoms have been linked to a host of stigma-related stressors and exacerbated by decreased access to competent and affirming formalized health care supports, particularly in the face of legislation aiming to curb access. As a result, intervention strategies that can be made widely available, accessed at no cost, and address these stressors to improve mental health and well-being are needed. This study presents findings from a self-administered online mental health intervention, titled Reflections to (re)Claim an Affirmed Identity to Improve Mental Health (RECLAIM), which used an expressive writing approach to address internalized anti-TGE stigma to reduce depressive and anxiety symptoms and improve perceived community connectedness. In this randomized controlled trial, 115 TGE community adults were assigned to one of three study conditions: two RECLAIM interventions and one expressive writing active control group. Analysis of between-group effects found that all three groups experienced similar levels of improvement in mental health over time, while within-group effects of time by condition demonstrated some notable differences in the overall trajectory of treatment or control effects. Overall, results of this randomized controlled trial provide preliminary empirical support for the efficacy of RECLAIM in reducing depressive and anxiety symptoms and internalized anti-TGE stigma and improving community connectedness. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Humans↗

PubMed2026

Implementation of Mobile Health Intervention Targeting Belongingness and Burdensomeness: An Ecological Momentary Assessment Study of Self-Injurious Thoughts and Behaviors in LGBTQ+ Individuals.

OBJECTIVE: The goal of this paper was to test a mobile health intervention designed to reduce self-injurious thoughts and behaviors in LGBTQ+ individuals. The intervention consisted of brief messages aimed at increasing feelings of belongingness and meaning. METHOD: We recruited LGBTQ+ individuals (N = 55) with past-month self-injurious thoughts and/or behaviors. Participants completed 14 days of ecological momentary assessment (EMA) of minority stress, thwarted belongingness, perceived burdensomeness, and self-injurious thoughts and behaviors. Then, participants were randomly assigned to receive brief messages designed to instill belongingness and meaning/purpose, or no intervention for 14 days. Then, participants completed an additional 14 days of EMA. RESULTS: Our results showed that participants in the control condition had significant increases in self-injurious thoughts and planning over time, whereas those in the intervention condition showed no significant change. For self-injurious behavior, thwarted belongingness, and perceived burdensomeness, there were significant decreases in the intervention condition, but no changes in the control condition. CONCLUSIONS: These results provide support for the interpersonal theory of suicide and indicate a potentially scalable mobile health intervention. PUBLIC HEALTH SIGNIFICANCE: This paper found evidence that a brief mobile health intervention reduced suicidal and non-suicidal self-injurious thoughts and behaviors among LGBTQ+ individuals.

Humans↗

PubMed2025

Distinct Behavioral Profiles and Neuronal Correlates of Heroin Vulnerability Versus Resiliency in a Multi-Symptomatic Model of Heroin Use Disorder in Rats.

OBJECTIVE: The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting the translational relevance of the mechanistic research that is conducted in experimental animals. The authors hypothesized that a nonlinear clustering of OUD-like behavioral traits would capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles. METHODS: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors. A nonlinear stochastic block model clustering analysis was used to assign rats to OUD vulnerable, intermediate, and resilient clusters. Additional behavioral tests and circuit analyses using c-fos protein activation were conducted on the vulnerable and resilient subpopulations. RESULTS: OUD vulnerable rats exhibited greater heroin taking and seeking behaviors relative to those in the intermediate and resilient clusters. Akin to human OUD diagnosis, further vulnerable rat subclustering revealed subpopulations with different combinations of behavioral traits, including sex differences. Lastly, heroin cue-induced neuronal patterns of circuit activation differed between resilient and vulnerable phenotypes. Behavioral sex differences were recapitulated in patterns of circuitry activation, including preferential engagement of extended amygdala stress circuitry in males and cortico-striatal drug cue-seeking circuitry in females. CONCLUSION: Using a nonlinear clustering approach in rats, the analysis captured behavioral diagnostic heterogeneity reflective of human OUD diagnosis. OUD vulnerability and resiliency were associated with distinct neuronal activation patterns, posing this approach as a translational tool in assessing neurobiological mechanisms underpinning OUD.

Animals↗