Latest Research on Gender Identity (2022-2026)

Scientific research on gender identity has undergone a significant acceleration over the past five years. New neuroimaging technologies, large-scale genomic studies, meta-analyses on hormone therapy, and longitudinal investigations on the persistence of gender identity in children and adolescents are reshaping the landscape of available knowledge. This article provides an overview of the main evidence published between 2022 and 2026, presenting the data in their complexity and allowing readers to assess the implications.

New Neuroimaging Studies

The ENIGMA Mega-Analysis and the Transgender “Brain Phenotype”

One of the largest structural studies ever conducted on transgender individuals is the mega-analysis by the ENIGMA Transgender Persons Working Group, published in the Journal of Sexual Medicine (Mueller et al., 2021) [1]. The study collected structural MRI data from 803 individuals not treated with hormones: 214 transgender men, 172 transgender women, 221 cisgender men, and 196 cisgender women. The results revealed significant differences in (sub)cortical volumes and cortical surface area between transgender and cisgender individuals, but not in cortical thickness [1]. The most relevant aspect is that the observed patterns did not simply position themselves along a male-female continuum: transgender individuals appeared to present a unique brain phenotype, not reducible to a shift toward either pole of sexual dimorphism [1].

The Amsterdam Cohort: Neuroimaging in Children and Adolescents

In 2024, a series of studies conducted on the Amsterdam cohort examined the neurobiological characteristics of children and adolescents with gender incongruence through functional MRI (fMRI) and diffusion tensor imaging (DTI) [2]. The results provided some evidence in favor of the sexual differentiation hypothesis at the functional level, meaning the idea that the brains of transgender individuals develop in a way more consistent with their perceived gender than with the sex assigned at birth [2]. However, at the structural level, the evidence was less clear. The authors also observed specific neural signatures in transgender individuals, suggesting that these may represent a distinct brain phenotype rather than a simple variation along the male-female spectrum [2].

Functional Connectivity and Trans Men

A pilot study published in 2024 in the Journal of Clinical Medicine used resting-state fMRI to compare the functional connectivity of 19 trans men diagnosed with gender dysphoria, 11 cisgender men, and 12 cisgender women [3]. The study identified specific connectivity differences among the three groups, confirming the hypothesis that trans men exhibit brain activity patterns that do not fully overlap with those of either cisgender men or cisgender women [3]. However, this was a pilot study with a limited sample, and the results require confirmation on a larger scale.

Effects of Hormone Therapy on the Brain

Research published in 2025 in Frontiers in Neuroscience examined differences in hippocampal subfield volumes between trans men undergoing testosterone treatment and cisgender women. Testosterone treatment was associated with an increase in total brain volume, gray matter volume, and cortical thickness. These data suggest a significant neuroplastic response to gender-affirming hormone therapy, but also raise the question of how much of the differences observed in neuroimaging are pre-existing to treatment and how much are induced by the therapy itself.

Genetics: GWAS and Genomic Studies

The Frontiers in Genetics Systematic Review (2023)

The first systematic review of the molecular and genomic bases of human sexuality, published by Bragazzi and colleagues in Frontiers in Genetics in 2023, examined genome-wide linkage (GWL) studies, genome-wide association studies (GWAS), genome-wide meta-analyses (GWAMA), and transcriptome-wide association studies (TWAS) [4]. The review confirmed that sexual behavior and gender identity have a complex polygenic architecture, influenced by many common genetic variants, each with very small but cumulative effects [4]. The largest GWAS, conducted by Ganna and colleagues in 2019 on 492,664 genomes, had identified five autosomal loci associated with same-sex sexual behavior, with genetic influence explaining between 8% and 25% of the variance, insufficient to predict the behavior of a single individual.

Twin Studies: Heritability of Gender Identity

A systematic review of the twin literature, published in Behavior Genetics in 2025, analyzed 16 studies that provided evidence for both genetic and environmental contributions to gender identity and gender-related behaviors [5]. Heritability estimates varied considerably, from 0.00 to 0.84 for gender identity, with non-shared environmental contributions ranging from 0.15 to 0.96 and shared environmental contributions from 0.00 to 0.70 [5]. Across an aggregated sample of 463 twin pairs, transgender concordance rates were 21.2% for monozygotic twins and 8.7% for dizygotic twins, with estimated relative risk ratios of 21.2 and 8.7 respectively (assuming a prevalence of 1%) [5]. These data suggest a substantial genetic contribution to gender diversity, while also confirming the importance of environmental factors.

Exome Sequencing and Rare Variants

Whole exome sequencing studies conducted on cohorts of transgender individuals have identified rare variants in genes associated with pathways involved in sexual differentiation of the brain and in the estrogen and estrogen receptor pathway. These findings, while preliminary and obtained from small samples, open a promising line of research into the specific genetic bases of gender identity, distinct from those of sexual orientation.

Limitations of Genetic Research

Genomic research on gender identity has significant limitations. Samples are often small, phenotypic definitions vary between studies, and most available GWAS data concern sexual orientation rather than gender identity per se [4]. The complexity of the genetic architecture makes it unlikely that a single “gender identity gene” will be identified, and current results instead indicate a multifactorial interaction between genetics, epigenetics, and environment [4][5].

Mental Health: Effects of Hormone Therapy

The Nature Human Behaviour Systematic Review (2023)

A systematic review published in Nature Human Behaviour by Baker and colleagues (2023) analyzed 46 scientific articles (6 qualitative, 21 cross-sectional, 19 prospective cohort) on the effects of gender-affirming hormone therapy (GAHT) on the psychosocial functioning of transgender individuals [6]. The results showed that GAHT was consistently associated with a reduction in depressive symptoms and psychological distress [6]. Evidence on quality of life was less uniform, with positive trends but not always statistically significant. Differences also emerged between masculinizing and feminizing therapy: some evidence suggested greater expression of anger (but not its intensity) in individuals on testosterone therapy [6].

The LEGACY Study — JAMA Network Open (2025)

The LEGACY cohort study, published in JAMA Network Open in March 2025, followed 3,592 transgender and gender-diverse adults at community health centers in Boston and New York for 48 months (2016-2019) [7]. 15.3% of participants had moderate to severe depressive symptoms, assessed with the Patient Health Questionnaire. GAHT was associated with a lower risk of moderate to severe depressive symptoms over the 48-month follow-up period [7]. This is one of the largest longitudinal studies conducted in a primary care setting for transgender individuals.

2024 Review of Mental Health Outcomes

A 2024 systematic review, published in the International Journal of Transgender Health, identified 29 studies (2,789 total participants) that quantitatively assessed mental health outcomes, including depression and anxiety, following affirmative interventions for gender dysphoria in adults [14]. The review confirmed a general trend toward improvement, while noting the heterogeneity of methodologies and the need for studies with more robust control groups [14].

Limitations of Current Evidence

Despite positive trends, the literature has acknowledged limitations: often small samples, lack of adjustment for confounding variables, absence of randomization (generally considered unethical in this context), and variability in measurement instruments. These factors limit the ability to establish definitive causal relationships.

Desistance and Persistence: What the Data Show

The Trans Youth Project (Olson et al., 2022)

The longitudinal study of the Trans Youth Project, published in Pediatrics in 2022, followed 317 young transgender individuals (208 trans girls, 109 trans boys; mean age 8.1 years at the start) for an average of 5 years after social transition [8]. 7.3% had undergone at least one retransition. At the end of the observation period, 94% identified as binary transgender, 2.5% as cisgender, and 3.5% as non-binary [8]. Subsequent cisgender identities were more common among youth whose initial social transition had occurred before age 6, with retransitions often occurring before age 10 [8].

The German Insurance Data Study (Bachmann et al., 2024)

A 2024 study, published in Deutsches Arzteblatt International, analyzed German health insurance data on 7,885 young people aged 5 to 24 with a coded F64 diagnosis (gender identity disorders) in the period 2013-2022 [9]. The results showed that only 36.4% maintained a confirmed F64 diagnosis after five years, with diagnostic stability below 50% in all age groups [9]. Prevalence had increased 8-fold over the decade, with adolescent females showing the highest prevalence (452.2 per 100,000) and the most marked increase (12-fold) [9].

This study generated debate: critics observed that the loss of a coded diagnosis in insurance data does not necessarily equate to clinical desistance, as it may reflect changes in physician, treatment interruptions for non-clinical reasons, or simple variations in diagnostic coding.

Desistance and Detransition in Adults

A 2023 study, published in Archives of Sexual Behavior, recruited 78 U.S. individuals between 18 and 33 years old who had stopped identifying as transgender at least six months before participation [13]. On average, participants had identified as transgender starting at age 17.1 and had done so for 5.4 years. Participants reported a significant improvement in psychological health after detransition, with reductions in self-harm and gender dysphoria [13]. The study, however, used a self-selected and non-representative sample, which limits its generalizability.

Methodological Reflections

Desistance rates vary enormously between studies (from 7% to 64%), depending on the population studied, the definition of desistance used, the age of participants, and the recruitment method. Older studies, often cited for high desistance rates, have been criticized for including in the sample children who did not meet the diagnostic criteria for gender dysphoria. More recent research tends to draw a sharper distinction between clinically significant gender incongruence and gender non-conforming behaviors in childhood.

Transgender Adolescents: Evidence on Puberty Suppression

The Miroshnychenko et al. Systematic Review (2025)

The most recent systematic review and meta-analysis on puberty suppression in youth with gender dysphoria, published in Archives of Disease in Childhood in 2025, included 10 studies: 3 comparative observational studies and 7 before-after studies [10]. The comparative studies provided evidence of very low certainty on global functioning and depression, while the before-after studies provided evidence of very low certainty on gender dysphoria, global functioning, depression, and bone mineral density [10]. The authors concluded that considerable uncertainty remains about the effects of puberty blockers in youth with gender dysphoria, and that methodologically rigorous prospective studies are needed [10].

The Cass Review (2024) and the International Debate

The Cass Review, the final report of the independent inquiry commissioned by the National Health Service (NHS) in England and published in April 2024 under the guidance of Dr. Hilary Cass, represented the most comprehensive review of evidence on gender care for minors in the British context [11]. The report incorporated multiple systematic reviews conducted by the University of York and covered clinical pathways, social transition, puberty blockers, hormonal treatments, and psychosocial treatments.

Key recommendations included limiting puberty suppression with GnRH analogs to clinical trial settings only and a more cautious, individualized approach to the care of adolescents with gender incongruence [11]. The British government subsequently banned the prescription of GnRH analogs as gender-affirming treatment for minors.

The Cass Review generated heated debate. Criticism came from multiple directions. On one side, organizations such as the International Lesbian, Gay, Bisexual, Trans and Intersex Association (ILGA), Transgender Europe, and IGLYO published a joint statement criticizing “poor and inconsistent use of evidence, pathologizing approaches, and the exclusion of service users and trans health experts.” In July 2024, the World Professional Association for Transgender Health (WPATH) and USPATH published a formal response contesting several methodological aspects of the report. An analysis published in the International Journal of Transgender Health argued that the Review’s recommendations did not always derive from the data presented in the supporting systematic reviews [12].

On the other side, some researchers and clinicians welcomed the report, emphasizing the need for higher evidentiary standards and greater caution in prescribing irreversible medical interventions to adolescents.

The International Landscape

The Cass Review influenced the debate well beyond the borders of the United Kingdom [11]. Sweden, Finland, and Denmark had already adopted more restrictive approaches in the preceding years. Meanwhile, guidelines in other countries, such as the German guidelines for the diagnosis and treatment of gender incongruence in children and adolescents updated in 2025, sought a balance between protecting minors and ensuring access to necessary care.

Recent Meta-Analyses: The State of the Art

Quality of Evidence

The most recent systematic reviews converge on one point: the overall quality of evidence in gender medicine for minors is low or very low by the standards of evidence-based medicine [10]. This does not mean that treatments are necessarily ineffective, but that the available studies have significant methodological limitations, including small samples, the absence of randomized control groups, a high risk of bias, and insufficient follow-up.

For adults, the evidence is more robust, especially regarding the effects of hormone therapy on depressive symptoms and psychological distress [6][7][14], although gaps remain in understanding long-term outcomes.

Convergences and Divergences in the Literature

Some areas show growing convergence in recent scientific literature:

• Transgender individuals exhibit brain patterns that do not simply lie along a male-female continuum but constitute a distinct phenotype [1][2].
• Gender identity has a significant genetic component, but one that is multifactorial and not reducible to single genes [4][5].
• Gender-affirming hormone therapy is associated, in most studies, with improvements in depressive symptoms and psychosocial functioning in adults [6][7][14].

Other areas remain the subject of active scientific debate:

• The long-term efficacy and safety of puberty suppression in minors [10][11].
• The actual desistance rates and their clinical significance [8][9][13].
• The risk-benefit balance of medical interventions in adolescents, in a context of rapidly increasing diagnoses [9][11].

Toward More Rigorous Research

The international scientific community recognizes the need for large-scale prospective studies, with extended follow-ups, appropriate control groups, and standardized outcome measures. Several research programs are currently underway in Europe and North America to fill these gaps. In the meantime, clinical decisions continue to be based on the best available evidence, integrated with clinical judgment and the informed preferences of patients and, in the case of minors, their families.

The challenge for the coming years will be to produce sufficiently robust data to guide balanced health policies, avoiding both over-medicalization and excessive restriction of access to care, in a field where science and public debate are closely intertwined.