Review Article

Rapid review of gender-affirming healthcare for children and adolescents: Evidence synthesis (2021–2025) and recommendations for South Africa

Ingrid Lynch, KL Dunkle, Chris McLachlan, Pierre Brouard, Landa Mabenge, Sakhile Msweli, Liberty Matthyse, Marion Stevens, Robin Dyers, Jenna-Lee de Beer-Procter, Kevin Adams, W.D. Francois Venter, Elma de Vries

Received: 23 Dec. 2025; Accepted: 02 Apr. 2026; Published: 28 Aug. 2026

Copyright: © 2026. The Author(s). Licensee: AOSIS.
This work is licensed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).

Abstract

Background: Since the publication of the Southern African HIV Clinicians Society Gender-Affirming Healthcare (GAHC) Guideline in 2021, global evidence on care for transgender and gender-diverse (TGD) youth has expanded. An updated, locally grounded, evidence-informed assessment of health outcomes can support South African stakeholders, particularly as both adolescents and TGD persons are populations of relevance to HIV prevention, sexual health, and integrated healthcare programmes in South Africa.

Objectives: To synthesise global empirical evidence (2021–2025) across psychosocial, endocrine, surgical, policy, and non-medical gender-affirming interventions for TGD youth under 18, with attention to South Africa’s social, legal, and health-system, and HIV-service delivery context.

Method: A rapid review was conducted across 12 databases, supplemented by targeted searches for recent systematic reviews. Eligible sources comprised peer-reviewed empirical studies (N ≥ 5) reporting psychosocial or physical health outcomes of relevant interventions for TGD youth under 18 (or their families), and systematic or grey-literature reviews with reproducible methods. Findings were synthesised narratively by intervention domain.

Results: The review included 200 primary studies, 29 academic systematic reviews, and four grey-literature reviews. Affirming psychosocial interventions were associated with reduced distress, anxiety and suicidality, and improved functioning and belonging. Puberty blockers and hormone therapy produced expected physiological outcomes under specialist care, with generally mild adverse events and stable or improved mental health. Restrictive policies were linked to poorer mental health, while protective policies improved outcomes. Most studies were small, observational, and Global North-focused.

Conclusion: Evidence supports the safety and effectiveness of GAHC for TGD youth. Strengthening affirming care, timely clinical access, and protective policies in South Africa may improve healthcare engagement and support the delivery of integrated adolescent, sexual health, and HIV-related services for TGD youth.

Keywords: gender-affirming healthcare; transgender and gender diverse; transgender health; gender affirmation; psychosocial support; gender-affirming hormone therapy; gender-affirming surgery; South Africa; sexual health; HIV prevention.

What this study adds: This rapid review of evidence indexed January 2021 to August 2025 indicates that GAHC for TGD youth improves well-being, reduces psychological distress, prevents harm, and supports healthier developmental and mental-health outcomes. Findings inform South African HIV and sexual health practice and policy. This review updates the evidence underpinning the GAHC Guideline and provides clinically relevant evidence for multidisciplinary teams delivering HIV, sexual, reproductive, and adolescent healthcare services.

Introduction

Transgender and gender-diverse (TGD) is an umbrella term referring to people whose current gender identities do not align with the sex assigned to them at birth.¹ Adolescents within this group experience some of the greatest barriers to accessing healthcare globally.² In South Africa, research has documented a high prevalence of HIV among transgender women,³ substantial healthcare access barriers for TGD people,^4,5 and evidence that access to gender-affirming hormone therapy (GAHT) is associated with improved engagement across the HIV continuum of care, including viral suppression.⁶ The National Strategic Plan for HIV, TB and STIs 2023–2028 identifies both adolescents and TGD persons as priority populations for interventions, and calls for the inclusion of gender-affirming services across all levels of care.⁷

Since publication of the 2021 Southern African HIV Clinicians Society (SAHCS) Gender-affirming Healthcare (GAHC) Guideline,⁸ the evidence base on GAHC for children and adolescents has expanded substantially. This body of literature spans a wide range of study designs, scopes, and quality, and has been generated predominantly in Global North settings. In parallel, numerous systematic reviews,^{9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36} evidence syntheses,^37,38,39,40 and updated international clinical guidelines^{1,41,42,43,44,45} have been released. Taken together, these developments underscore a pressing need among South African stakeholders – including TGD youth, their families and caregivers, educators, mentors, and clinicians – for a comprehensive, rigorous, and transparent synthesis of emerging evidence that is interpreted through local constitutional, historical, and socio-cultural commitments. These commitments shape health policy, clinical practice, and rights-based care in South Africa, including constitutional protections for gender identity as affirmed through equality jurisprudence.^46,47,48 While global debates are often shaped by political and cultural dynamics specific to the Global North,^{49,50,51,52,53} South Africa must assess emerging evidence in relation to its own constitutional and public health frameworks, including the principles of Ubuntu, Batho Pele, equity, and collective well-being.^54,55,56 Moreover, the South African context is shaped by health system inequities – including medication stock-outs, provider shortages, and the concentration of services in urban tertiary centres – that affect access to and continuity of care.^4,57,58,59 These constraints are critical to interpreting the global evidence base within South Africa.

The conceptualisation of this review arose through collaboration between the SAHCS, as custodians of the 2021 GAHC Guideline⁸; original authors of the Guideline; Gender DynamiX, a South African transgender advocacy organisation that partnered in developing the Guideline; and the Professional Association for Transgender Health South Africa (PATHSA), which was formed in 2020. PATHSA endorsed the Guideline in 2021 as a professional body supporting the development and stewardship of GAHC practice in South Africa.

This independent rapid review synthesises research indexed from 01 January 2021 to 14 August 2025 to evaluate whether new evidence supports updates to or refinements of the 2021 SAHCS GAHC Guideline.⁸ Its overall aim is to collate findings from recent empirical research to support evidence-informed South African clinical practice and the development of a future guideline intended to supersede the 2021 SAHCS GAHC Guideline. The review was conducted by a gender and sexually diverse South Africa-based team with methodological, clinical, and lived-experience expertise. This perspective informed interpretation of retrieved evidence through an equity-oriented, rights-based, and context-sensitive lens. Full partnership with knowledge users strengthens evidence synthesis⁶⁰ by ensuring that analyses engage with realities of unequal access, historical trauma, and structural barriers that characterise healthcare experiences for many TGD young people in South Africa.^4,5,6,61,62

Objectives

The review sought to:

• Synthesise global empirical evidence indexed between January 2021 and August 2025 across all types of GAHC interventions for TGD youth under 18, with attention to both benefits and potential harms.
• Assess the alignment between emerging evidence and the 2021 SAHCS GAHC Guideline, identifying where new findings support, refine, challenge, or extend existing recommendations.
• Interpret global findings within South Africa’s constitutional, health-system, and socio-cultural context, including historical inequities and intersecting structural barriers – such as poverty, violence, stigma, racism, sexism, xenophobia, homophobia, transphobia and cisnormativity – that shape health risks, access to care, and lived experience.

In doing so, this rapid review aims to support healthcare providers, policymakers, educators, civil society, and families in delivering care that is evidence-informed, developmentally appropriate, and aligned with the rights and dignity of TGD youth.

Research methods and design

A rapid review approach was adopted to balance methodological rigour with timeliness.^60,63,64 Rapid reviews apply systematic review principles while streamlining elements such as screening processes and data extraction to produce timely, policy-relevant evidence within constrained timeframes.⁶³ This approach was selected to inform planned updates to the 2021 GAHC Guideline while maintaining transparency and analytic integrity. To enhance relevance to clinical practice and lived realities, the author team comprised TGD community members, clinicians who care for TGD youth, and guideline developers and implementers, whose combined expertise informed methodological decisions and interpretation of findings.⁶⁰

The search protocol was developed to reflect the following a priori aims, with each domain assessed for all reported outcomes, including both benefits and risks, and with openness to additional categories of intervention emerging inductively from the literature:

• Psychosocial and supportive interventions: What is the emerging evidence on psychosocial interventions for TGD youth under 18, including different approaches to mental healthcare, peer or community support, family and parental/caregiver support or lack thereof, and school-based interventions?
• Endocrine interventions: What is the emerging evidence on endocrine interventions for TGD youth under 18, including puberty-pausing medication, GAHT, and other endocrine therapy?
• Surgical interventions: What is the emerging evidence on gender-affirming surgeries for TGD youth under 18, including masculinising chest surgery and other relevant procedures?
• Legal, policy, and structural environments: What is the emerging evidence on the health impacts of legal, policy, systemic and structural interventions shaping GAHC for TGD youth under 18?

Eligibility criteria

Included publications:

• Peer-reviewed primary studies (N ≥ 5) reporting psychosocial or physical health outcomes of interventions for TGD youth (< 18), including interventions involving family systems, caregivers, educators, or broader public environments.
• Systematic, scoping, and narrative reviews with transparent, reproducible search and screening protocols.
• Grey-literature systematic reviews meeting equivalent methodological standards.
• Studies reporting family-level outcomes, where data specific to TGD youth were disaggregated and presented.

Excluded publications:

• Non-empirical publications, including reviews without published and reproducible protocols, commentaries, think pieces, editorials, and opinion pieces.
• Studies without psychosocial or physical health outcome data for TGD youth (< 18). Proxy-reported data from families or healthcare providers were permitted. For studies of sexual and gender minority youth, separately analysed data for at least five TGD youth were required.
• Case reports or case series with N < 5 were excluded. Composite or hypothetical examples were not counted towards N.

Given the diversity of interventions and outcomes, precise Population-Intervention-Comparator-Outcome-Time (PICOT) criteria could not be predefined. However, inclusion criteria were aligned as closely as possible to these frameworks, as shown in Table 1.⁶⁵

All empirically assessed psychosocial and health outcomes and all empirical study designs (quantitative, qualitative, and mixed methods) were eligible. Meta-analysis was not feasible because of extreme heterogeneity in populations, interventions, and outcome measures; findings are therefore synthesised narratively. The full technical report, available at https://pathsa.org.za/resources/rapid-review-2025, adheres to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 reporting standards,⁶⁶ with transparently reported streamlining adaptations consistent with interim published guidance for rapid reviews.⁶⁴

Search strategy, screening and selection

Searches were conducted on 26 November 2024, 04 December 2024, and 14 August 2025 across 12 databases via EBSCOhost (University of Pretoria), supplemented by searches of ClinicalTrials.gov and the International Standard Randomised Controlled Trial Number (ISRCTN) registry, and targeted searches for recent systematic reviews. Search date limits were set to capture records indexed between 01 January 2021 and 31 December 2025, thereby including articles indexed online ahead of their recorded publication dates. The search strategy combined [any term for trans and gender diverse identity] AND [any term for youth under 18] AND [any term for interventions related to gender identity]. Full search strings are provided in the technical report. No language restrictions were placed on the search results. Titles and abstracts of non-English sources were screened based on publisher-provided English translations whenever available and supported by Google Translate as needed.

Data extraction and analysis

Two custom Airtable-based tools were used to extract data from primary studies and systematic reviews, capturing study characteristics, populations, interventions, outcomes, and key results. Data extraction for non-English sources was based on publisher-provided English translations in all but one case, where the full text of a Spanish-language article was translated using Google Translate. The machine-translated text was reviewed alongside the original article, with key passages verified by a Spanish-speaking research assistant. Formal de novo risk-of-bias or certainty grading across all individual studies was not undertaken; instead, where available, methodological appraisals and certainty assessments reported in included systematic reviews were used qualitatively to inform interpretation.

Data extraction from full-text sources was conducted by authors KL Dunkle and Ingrid Lynch. Two large language models (LLMs), ChatGPT and Perplexity, were used in a limited, supportive capacity. A structured data-extraction prompt was applied to individual PDFs to generate draft plain-text data extraction elements aligned with predefined Airtable fields. These drafts were line-checked against the original sources, corrected where necessary, and manually entered the extraction database. LLMs were instructed to flag missing, ambiguous, or uncertain data elements for targeted human review, and all errors and gaps were resolved by the human reviewers using the original reports.

LLMs were also used on an ad hoc basis to cross-check draft narrative descriptions of results against spreadsheets of the extracted data and source PDFs, supporting identification of potential omissions or internal inconsistencies for human correction. LLMs were not used for study screening, inclusion–exclusion decisions, formal analysis, recommendation development, conflict-of-interest statements, or contextual framing. All LLM-generated outputs were treated as provisional drafts and were reviewed, verified, and rewritten by the human author team prior to inclusion.

Narrative synthesis of findings

Narrative syntheses drew on structured Airtable data extractions, with attention to intervention type, outcome measures, study design, sample characteristics, follow-up duration, and any certainty ratings reported in prior reviews. Findings were organised across five domains of care: psychosocial, endocrine, surgical, non-medical gender-affirming practices, and policy and legal interventions. Domain leads verified that narrative summaries accurately reflected underlying data and appropriately characterised any methodological uncertainty. The synthesis prioritised practice-relevant findings and patterns in relation to benefits, harms, and equity and access considerations, while explicitly noting where evidence was sparse, methodologically weak, or inconsistent.

Three cross-cutting interpretive lenses guided synthesis:

• Global scope and local gaps, highlighting where South African/Global South evidence remains absent.
• Equity and context, examining whether and how studies addressed intersecting axes of inequality.
• Policy and practice relevance, focusing on implications for South African clinicians, families, policymakers, and guideline developers.

Finally, to strengthen practice relevance, synthesised findings were assessed against the 2021 SAHCS GAHC Guideline.⁸ For each intervention domain, evidence was considered in terms of direction of effect, consistency, methodological quality, follow-up duration, and relevance to the South African context. Implications for existing Guideline recommendations were classified as:

• Consistent – emerging evidence aligns with current guidance.
• Refine – emerging evidence suggests that current guidance could be sharpened or made more specific.
• Challenge – emerging evidence contradicts current guidance or introduces caveats.
• New content area – emerging evidence highlights an area not addressed in current guidance.

These classifications were reviewed iteratively by the full author team, with reference to the synthesised evidence, to ensure analytic coherence and contextual appropriateness.

Results

The final dataset comprised 200 primary studies, 29 academic systematic reviews, and four grey-literature systematic reviews, yielding 233 included sources.

The PRISMA diagram (Figure 1) details the identification, screening, and inclusion process, including duplicate removal, automated exclusions of ineligible publication types, and abstract and full-text screening.^66,67

FIGURE 1: PRISMA diagram showing flow of literature searches, exclusions and inclusions of retrieved sources.

The complete list of primary studies and systematic reviews, along with extracted data, is provided in the Online Supplementary Appendix (Table S-A and Table S-B).

Overall, 108 of the 200 included primary studies had been described in at least one systematic review in our dataset. We also retrieved 92 primary research articles that were not included in any of the prior systematic reviews identified here. The inclusion of these 92 studies increases the primary literature base considered in this report by 85.2% relative to that synthesised in the retrieved review literature. Table S-C in the Online Supplementary Appendix maps each primary study to the systematic review(s) in which it appeared and reports formal certainty appraisals, where available. For studies included in multiple reviews, certainty assessments varied according to the research questions and methods applied in each review; notes and critiques on how these were conducted appear in Table S-B and Table S-C (see Online Supplementary Appendix).

In the remainder of our analyses, prior systematic reviews were treated as evidence sources in their own right and used qualitatively to contextualise patterns and the certainty of evidence in the primary studies; however, care was taken to avoid over-emphasising primary studies appearing in multiple reviews. Synthesis and conclusions are grounded in the full source dataset, with insights from prior reviews informing interpretation rather than driving analysis.

Psychosocial interventions and support

We identified 53 primary studies,^{68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120} 12 academic systematic reviews,^{10,11,13,15,19,20,22,23,24,31,36,121} and three grey-literature systematic reviews^37,38,39 examining psychosocial aspects of care for TGD children and adolescents. The full list of primary studies is provided in Table S-D in the Online Supplementary Appendix. The evidence base is methodologically heterogeneous and dominated by observational and qualitative designs, with the majority comprising cross-sectional surveys or retrospective clinic-based analyses.^{72,76,77,85,91,92,93,94,96,99,100,102,103,104,106,108,109,112,113,117,118,119,120} A substantial proportion of studies used qualitative or mixed methods designs, drawing on interviews with young people, caregivers, families, or clinicians to explore experiences of support, identity development, barriers to access, and care processes.^{70,79,80,84,87,88,90,93,98,101,105,110,111,114}

Affirming psychosocial practices such as supporting a young person’s gender expression,^{19,69,83,89,91,93,94,115,117} strengthening family and peer connectedness,^{10,22,36,76,81,85,92,104,106,109} creating safer school environments,^{11,36,86,93,95,100,102,108,113,118,121} and providing tailored psychological or digital interventions^{37,68,71,73,74,75,79,120} are associated with reductions in depression, anxiety, and suicidality, as well as improvements in resilience, sense of belonging, school participation, and daily functioning. However, access to affirming support is not evenly distributed, with nonbinary youth and racially marginalised TGD youth reporting lower levels of gender affirmation and support across social and care contexts.^91,104 No included study or systematic review reported harms attributable to affirming psychosocial care.

By contrast, non-standard or pathologising practices – including identity-change efforts, enforced or non-clinical delays in social affirmation, or withholding affirmation – which fall outside recognised standards of psychosocial care, are consistently associated with adverse outcomes, including heightened distress, self-harm, suicidality, and deteriorating family relationships.^{38,77,87,94,111}

Most studies are cross-sectional, self-reported, and concentrated in high-income settings, with relatively few longitudinal or experimental designs; these factors limit certainty of evidence in individual reports. Nonetheless, the consistency of findings across survey-based, qualitative, and mixed-methods studies, alongside diverse care contexts and outcome measures, supports psychosocial affirmation as both safe and beneficial. Taken together, findings underscore that mental health outcomes are shaped by family, school, and community contexts, and highlight the importance of supporting children and adolescents who face inconsistent or unsupportive family environments. Findings also point to the need to support youth facing overlapping social and structural stressors, and to ensure equitable access to affirming psychosocial support across diverse social, educational, and community settings.

Overall, the evidence on psychosocial interventions and support for TGD youth is consistent with the 2021 SAHCS GAHC Guideline recommendations. Table 2 summarises key implications for guideline development, mapping synthesised evidence against existing guidance and highlighting areas of support and refinement.

Endocrine interventions

We identified 23 primary studies,^{122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144} three academic reviews,^26,28,33 and one grey-literature report³⁹ with focused evaluation of puberty-pausing medication; 28 primary studies,^{145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172} and two academic reviews^25,32 with focused evaluation of GAHT; and 53 primary studies,^{78,87,88,153,154,155,156,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219,220} 11 academic reviews^{9,11,12,16,17,18,21,27,29,34,35} and three grey-literature reports^37,38,40 with joint or overlapping evaluation of puberty pausers and GAHT (see Online Supplementary Appendix: Table S-E, Table S-F and Table S-G).

The literature shows a consistent pattern: endocrine interventions for TGD adolescents generally achieve their intended physiological effects^{25,32,33,37,38,40,124,126,203}; adverse events are typically anticipated, predominantly mild, and manageable under routine monitoring in specialist care, with specific adverse events described in relation to individual interventions below.^{123,124,131,146,150,173} Mental-health outcomes are broadly stable or improved.^{122,127,142,166,209} Although the evidence base is methodologically constrained and concentrated in high-income clinical settings, available data provide a short- to medium-term picture of effectiveness and safety.^{9,21,27,34,35}

Puberty-pausing medication reliably halts unwanted pubertal development,^{39,124,126,130,136,142,143} and GAHT induces expected masculinising or feminising changes.^{25,32,37,38,150} Endocrine and metabolic parameters typically remain within clinically acceptable ranges under supervised care.^{124,140,150,210} Bone-density reductions during pubertal suppression are common and well-described,^{125,132,137,195} and typically show partial or substantial recovery following subsequent GAHT or endogenous puberty, especially when progression to hormones is timely and aligned with clinical indicators.^{125,175,197,203,207,213} Serious adverse events are rare across endocrine pathways, with no consistent pattern of irreversible harm.^{149,173,204,216,220}

Mental-health outcomes are heterogeneous at the individual level, yet broadly stable-to-favourable across cohorts. Adolescents who access puberty suppression and/or GAHT generally show reductions in depressive symptoms and suicidality, alongside improved appearance congruence and functioning, compared with their own baseline and with peers who want but cannot access treatment.^{160,161,164,166,181,194,209} Worsening mental-health trajectories are more consistently associated with delayed or restricted access to care than with endocrine treatment,^166,209 with GAHT linked to lower risks of suicidality-related emergency or inpatient care and to fewer mental-health diagnoses and psychiatric hospitalisations following treatment initiation.^192,200

Longitudinal data indicate high continuation into adulthood and very low reported regret among adolescents who commence endocrine care.^{153,154,156,212,213} Where discontinuation occurs, it is very often linked to external or structural factors (such as access barriers, service disruptions, costs, insurance denials, family stressors, or bullying), completion of desired physical changes, or evolving identity-related needs, rather than to treatment-related side effects or regret.^{16,153,154,163,184}

Although menstrual suppression as gender-affirming care is not explicitly addressed in the 2021 SAHCS GAHC Guideline, review of evidence from five primary sources^{221,222,223,224,225} (Online Supplementary Appendix: Table S-H) suggests that it is a safe, effective, and highly valued component of care for TGD adolescents who menstruate. Reported outcomes include high rates of amenorrhoea, reduced pain and menstrual-related dysphoria, and high overall satisfaction, with mild and infrequent adverse events.^{221,222,223,224,225}

Fertility preservation was addressed in 16 primary sources^{226,227,228,229,230,231,232,233,234,235,236,237,238,239,240,241} (Online Supplementary Appendix: Table S-I), one academic systematic review,³⁰ and two grey-literature reviews.^37,38 Although gamete preservation appears feasible and generally safe for adolescents, interest is typically low, and accessibility for those who are interested is substantially constrained by cost, procedural dysphoria, and timing of referral.^{37,38,226,227,229,230,231,232,233,234,235,236,237,238,239,240,241} These factors highlight the importance of early, developmentally appropriate, and iterative fertility counselling.

Overall, the evidence aligns with the 2021 SAHCS GAHC Guideline recommendations. Table 3 and Table 4 summarise key implications for guideline development for puberty pausing and GAHT, respectively, mapping synthesised evidence against existing recommendations. Table 5 outlines implications for future guideline development related to menstrual suppression.

Surgical interventions

We identified 10 primary studies reporting outcomes of gender-affirming surgery in adolescents,^{242,243,244,245,246,247,248,249,250,251} and 15 primary studies in which surgery was examined within broader gender-affirming care trajectories that also included endocrine and/or psychosocial care^{163,184,196,213,228,252,253,254,255,256,257,258,259,260,261} (Online Supplementary Appendix: Table S-J1 and Table S-J2). Two grey-literature systematic reviews assessed surgical outcomes in youth.^37,38

Evidence for patients under age 18 is limited in volume but highly consistent, focusing almost entirely on masculinising chest reconstruction, which is the only gender-affirming surgery routinely accessed by adolescents.^{242,243,244,245,246,247,248,249,250,251} A very small number of other procedures (e.g. hysterectomy, vaginectomy, facial feminisation) are reported in United States national registry data, but are vanishingly rare in under-18s.²⁴⁵ Within multidisciplinary programmes, masculinising chest surgery shows very low complication and revision rates, with safety profiles favourably comparable to those observed in adults or cisgender youth undergoing analogous chest procedures.^{242,244,245,249,250}

Psychosocial outcomes of gender-affirming surgery are consistently positive in the short to medium term, including improved body image, reduced dysphoria, and increased participation in social, educational, and physical activities, alongside high levels of patient satisfaction.^{37,38,243,247,250,251} Reported regret is rare, including in the few longer-term follow-up studies that are available.^{37,247,249,250} Studies examining surgical interventions within broader gender-affirming care trajectories report similarly favourable safety and psychosocial outcomes, reinforcing findings from surgery-specific cohorts.^{163,184,196,213,228,252,253,254,255,256,257,258,259,260,261} Adolescents considering or recovering from surgery benefit from ongoing care from multidisciplinary teams, affirming family support, and peer networks.^228,256,259 These findings reinforce the importance of situating surgical interventions within broader trajectories of gender affirmation, including ongoing psychosocial support.

Findings are consistent with the 2021 GAHC Guideline recommendations. Table 6 summarises key implications for guideline development and identifies areas for potential refinement.

Non-medical gender-affirming practices

We identified one large online survey²⁶² (Online Supplementary Appendix: Table S-K) and one narrative review¹⁴ addressing non-medical gender-affirming practices, including binding, tucking, packing, and padding. Although the evidence base is limited, findings indicate that these practices are meaningful tools through which TGD adolescents manage gender dysphoria, navigate public and social spaces, and feel more at ease in their bodies.^14,262 For many adolescents, these practices are partly driven by limited or delayed access to endocrine and/or surgical GAHC. The available evidence does not indicate serious health risks associated with packing or padding. Physical discomfort related to binding and tucking appears to be common but manageable when TGD youth have access to safer materials and practical guidance.^14,262

Policy and legal interventions

Although policy and legal interventions are not addressed as a standalone domain in the SAHCS GAHC Guideline (2021), this rapid review identified eight studies examining the health impact of laws, regulations, and/or administrative systems on TGD youth^{111,261,263,264,265,266,267,268} (Online Supplementary Appendix: Table S-L). No systematic reviews were identified.

Across both qualitative and quantitative studies, restrictive laws and systemic barriers – including outright healthcare bans, regulatory constraints, and administrative obstacles – are consistently associated with poorer mental-health outcomes, including heightened depression, anxiety, suicidality, and social isolation among TGD youth.^{111,261,263,264,265,266,267,268} These associations are observed following both enacted policies and periods of policy uncertainty, suggesting that anticipatory stress and disruption to care pathways contribute to harm.

Conversely, affirming and protective policy environments, including anti-discrimination protections, inclusive institutional guidance, and accessible legal gender recognition, are associated with improved mental-health indicators and, in some analyses, lower substance use and other risk behaviours, as well as enhanced overall well-being.^261,265,267

Parental and caregiver accounts mirror these findings, describing how proposed or enacted care bans intensified depression, anxiety, suicidality, and family distress, particularly where policies disrupted ongoing treatment or created prolonged uncertainty.^263,264,266 Across studies, families reported increased emotional burden, logistical strain, and fear related to maintaining access to care within hostile or unstable policy environments.^263,264,266

Discussion

The global evidence base on GAHC for TGD children and adolescents has expanded rapidly since the publication of the SAHCS GAHC Guideline in 2021. Across psychosocial, endocrine, surgical, non-medical and policy interventions, the evidence from 2021 to 2025 demonstrates a consistent pattern across diverse study designs and contexts: when TGD children and adolescents receive GAHC within supportive familial, social, educational, clinical, and policy environments, outcomes are generally stable or improved, and harms are rare. Conversely, the evidence indicates that non-clinical delays in providing GAHC, as well as hostile familial, social, educational and policy environments, are associated with worsening distress and poorer mental-health outcomes. Across intervention domains, studies conducted within multidisciplinary care settings consistently report favourable safety and psychosocial outcomes, highlighting the importance of coordinated and integrated care across service levels.

Across intervention domains, the emerging evidence aligns with the 2021 SAHCS GAHC Guideline, reinforcing its core recommendations and ethical foundations, while also pointing to areas where future guideline refinements are warranted.

Strengths and limitations of this review

The review has several important strengths. It was conceived and led from South Africa by a gender and sexually diverse team with combined methodological, clinical, and lived-experience expertise. This positionality informed decisions about contextualisation and equity, ensuring that the synthesis remains grounded in the legal, social, and service realities of TGD youth in South Africa rather than importing assumptions from high-income settings. To our knowledge, this is the first comprehensive synthesis of GAHC evidence for people under 18 from the Global South.

The search strategy was broad and intentionally inclusive. We conducted a comprehensive multi-database search via EBSCOhost with no language restrictions, deliberately incorporating both current and pathologising terminology for TGD identities and interventions. Cross-mapping showed that 92 of 200 primary studies in our dataset had not appeared in any of the systematic reviews identified, substantially extending the evidence base available for synthesis and highlighting limitations in existing reviews. Data extraction and synthesis followed a structured and transparent process.

As is typical for rapid reviews, several methodological streamlining decisions were made. The review was not prospectively registered. After an initial dual-screening calibration phase, title and abstract screening proceeded with single review, with borderline or uncertain records flagged for second-reviewer input at abstract or full-text stage. Full-text screening and data extraction were not conducted in duplicate. We did not conduct a de novo, outcome-by-outcome risk-of-bias or GRADE/CERQual certainty assessment; instead, we drew on existing appraisals from previous systematic reviews where available and treated them as a secondary interpretive resource rather than as formal ratings for this review. No meta-analysis was attempted because of the extreme heterogeneity of designs, interventions, and outcomes. These choices are consistent with published guidance on rapid reviews, but they inevitably reduce the granularity of quality assessment and may increase susceptibility to subjective judgement compared with a fully resourced systematic review.^{60,63,64,269,270}

Nonetheless, the breadth of the search, the systematic cross-linking of primary studies and prior reviews, the large number of newly identified studies, and the structured narrative synthesis conducted by a multidisciplinary author team support the robustness and practical value of the findings. The review should therefore be understood as a transparent, contextually grounded rapid synthesis rather than a definitive systematic review, and its conclusions should be interpreted with reasoned discernment and attention to the underlying evidentiary limitations.

Strengths and limitations of the evidence base covered in this review

The evidence assembled in this rapid review – spanning 200 primary studies, 29 academic systematic reviews, and four grey-literature reports – demonstrates a consistent pattern across psychosocial, endocrine, surgical, non-medical, and policy interventions. When TGD young people access affirming psychosocial support, timely endocrine care, and, for older adolescents who require it, surgical interventions, improvements are seen in mental health, dysphoria, and day-to-day functioning. Serious adverse events are rare. Systematic reviews published since 2021, including those commissioned in politically conservative policy environments, echo these findings and report no evidence of population-level harm.^{9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,37,38,39,40,121} This consistency across diverse study designs and outcome domains strengthens confidence in the overall direction of effect, even where formal certainty ratings remain low.

Important limitations in the evidence remain. Most primary studies are observational and/or clinic-based, with small, non-representative samples, short follow-up, and limited geographic diversity. Randomised or quasi-experimental designs are scarce; they are rarely feasible or ethical in this area of care.²⁷¹ Evidence for endocrine and surgical care currently relies heavily on retrospective chart reviews, with variable data quality, inconsistent outcome recording, and limited use of patient-reported measures. Frequent access to multiple and concurrent gender-affirming intervention types by individual TGD youth constrains precision in assessing the impact of particular interventions and requires methodological advancement in the field to disentangle causality while preserving patient autonomy.

Systematic reviews reflect these constraints. Across reviews, varying assessment approaches consistently rate the certainty of evidence as low to very low, because of design limitations, small sample sizes, overlapping patient populations and interventions, short follow-up periods, and narrow geographic scope, rather than conflicting findings. These gaps underscore the need for more robust, longer-term, and inclusive research from the Global South, and South Africa in particular, to better characterise evolving health needs and support equitable, contextually responsive health-system planning.

Clinical and policy decision-making in the context of low-certainty evidence

The certainty of the evidence surrounding GAHC for youth must be understood within the broader reality that low- and very low-certainty evidence underpins a substantial proportion of medical practice overall.^272,273,274 This is particularly true in paediatrics, where ethical and logistical constraints often preclude randomised trials and contribute to persistent inconsistencies across the evidence base, even for common childhood conditions such as asthma and epilepsy.^274,275

The recently updated GRADE Evidence-to-Decision (EtD) framework directly acknowledges these realities. As clarified in the 2025 Core GRADE 7 update,²⁷⁶ low-certainty evidence typically warrants a conditional recommendation, which is an explicit signal that clinicians must engage meaningfully in shared decision-making that centres patient values and preferences. Gordon Guyatt, leading architect of the GRADE framework and co-author of systematic reviews included in this synthesis,^25,26 has explicitly cautioned against the misuse of GRADE in policy advocacy against GAHC for youth.²⁷⁷ Guyatt and colleagues²⁷⁷ emphasise that low-certainty evidence should not be treated as justification for withholding care, but rather as a prompt for careful clinical decision-making that centres patient values, noting:

It is profoundly misguided to cast health care based on low-certainty evidence as bad care or as care driven by ideology, and low-certainty evidence as bad science. Many of the interventions we offer are based on low-certainty evidence […]. Thus, forbidding delivery of gender-affirming care and limiting medical management options on the basis of low-certainty evidence is a clear violation of the principles of evidence-based shared decision-making and is unconscionable.²⁷⁷

In South Africa, this is not simply a methodological consideration but a constitutional and statutory imperative. Section 129 of the Children’s Act²⁷⁸ requires respect for adolescents’ evolving capacity to participate meaningfully in decisions about their own healthcare. Where the overall evidence base offers low scientific certainty yet demonstrates consistent patterns across multiple domains and outcomes, the GRADE EtD framework requires clinicians to centre patients’ values, preferences, and lived experience – not to impose blanket restrictions or personal disapproval framed as clinical caution. This approach aligns with the informed-consent model endorsed in South African and international clinical guidelines on GAHC for youth.^1,8

Implications and recommendations for South Africa

In addition to the domain-specific comparisons with the 2021 SAHCS GAHC Guideline, the evidence synthesised in this review has broader clinical and policy implications that cut across intervention areas and highlight key principles for delivering safe, effective, and contextually grounded care:

• Affirmation is central to safe and effective care, reflecting both clinical evidence and South Africa’s constitutional and rights-based obligations.
• Multidisciplinary, coordinated care models that integrate medical, psychosocial, and community-based components, are associated with better outcomes across intervention domains, supporting continuity and safety of care over time.
• Structured and ongoing support for families and caregivers is essential, as affirming family environments are consistently linked with improved mental-health outcomes, sustained engagement in care, and enhanced daily functioning.
• Affirming psychosocial support should be integrated across all aspects of care, including clinical encounters, family engagement, and school or community settings, rather than treated as an ancillary component.
• Restrictive policies and administrative environments, including opaque referral structures, regulatory barriers, and medical-aid exclusions that limit affordability, are associated with delayed or disrupted access to care and related harms.
• Supportive and protective policy environments – such as those that prohibit discrimination, provide clear clinical guidance, and support continuity of care – are associated with improved population-level well-being, including lower distress and suicidality, greater resilience, and reduced reliance on acute mental-health and emergency services.
• Health system constraints, including medication stock-outs, long waiting lists, and uneven geographic distribution of clinical expertise, require targeted policy and planning responses, as these barriers leave many adolescents without feasible routes into care.
• Equitable financing mechanisms are needed, as financial exclusion disproportionately limits access to care for economically marginalised families and entrenches inequities across provinces, and between public and private healthcare sectors.
• Strengthening adolescent-friendly services and integrated care pathways enables many non-specialised components of gender-affirming care – including psychosocial support for young people and their families, menstrual suppression, trauma-informed counselling, management of co-occurring mental-health conditions, and safe referral pathways – to be delivered within routine adolescent health and mental-health services. This approach aligns with national priorities in HIV/SRHR, youth mental health, and adolescent-friendly service delivery.
• Timely access to GAHC is a matter of health equity and cost-effective prevention, given the documented harms associated with delayed care and its downstream impacts on schooling, psychological distress, and emergency mental-health utilisation.

Priorities for future research include expanding the evidence base in low- and middle-income countries, strengthening rigour and long-term follow-up, improving the visibility of non-binary adolescents in research, investigating intersecting structural determinants of health, extending evidence on menstrual suppression and adolescent fertility pathways, and deepening TGD youths’ involvement in co-produced and participatory research.

Conclusion

This rapid review provides empirical support that GAHC for TGD youth is evidence-informed, associated with improved well-being, prevents harm, and promotes healthier developmental and mental-health trajectories when delivered within supportive social, familial, clinical, and policy environments. The review affirms the evidentiary foundations of the existing South African GAHC Guideline and identifies opportunities to strengthen its implementation within South Africa’s legal, historical, and health-system context. While most available studies are observational, this reflects the ethical and methodological realities of paediatric research on interventions that cannot be logistically or ethically randomised or withheld. The consistency of findings across diverse settings therefore provides compelling, real-world evidence of effectiveness and safety.

Ultimately, this work reflects South Africa’s constitutional values, including dignity, equality, and the right to access healthcare without discrimination. South Africa has a long-standing tradition of protecting marginalised communities, guided by principles of collective care, justice and equity. Ensuring timely affirming care for TGD youth is both clinically sound and constitutionally grounded, representing a continuation of this legacy and a commitment to safeguarding the well-being of every young person entrusted to collective care.

Acknowledgements

The authors acknowledge Gender Dynamix for financial support, and PATHSA members for their ongoing encouragement and for modelling the collaborative spirit that anchors this work. Ariane Spitaels and Michelle Carrihill provided thoughtful input on the findings pertaining to endocrine interventions. Vanessa Mudaly assisted with abstract screening. Alasdair Allison, Rutendo Bothma and Brent Janse van Vuuren provided steady support and contributions throughout the project.

A preprint version of the full technical report was previously published on Research Square (https://doi.org/10.21203/rs.3.rs-8253372/v1), and we acknowledge its role in shaping the final article.

Artificial Intelligence Disclosure: During the preparation of this work, the authors used ChatGPT Plus (models o3 through 5.1) and Perplexity Pro to support a literature search, data extraction, and cross-check of extracted data. The content was reviewed and edited by the authors, who take full responsibility for its accuracy.

Ingrid Lynch, KL Dunkle, and Marion Stevens declare receiving consultancy fees for this project from Gender DynamiX. None of the other authors received remuneration for this work. Ingrid Lynch reports consultancy fees from Gender Dynamix (position paper on access to gender-affirming care), Afrikagrupperna (research on organised resistance to sexual and reproductive rights), Irise International (research on the global status of menstrual justice), and the IDRC, ICARS, and FiT-ED (gender-equity technical support). KL Dunkle declares past support from the CDC Cooperative Agreement with the SAMRC for training healthcare workers on post-violence support for LGBTQI+ survivors of violence, consulting fees from GBVF Response Fund1 (South Africa) and the Sexual Violence Research Initiative, travel support from Gender DynamiX for workshop attendance, serving as a DSMB member of Improving HIV testing, linkage, and retention in care for men through U = U messaging (1 R01 MH129223-01), and PATHSA and WPATH membership. Chris McLachlan declares receiving honoraria from Gender DynamiX and Outright International; travel support for meetings and conferences from WPATH, PsySSA African Human Rights Project, Outright International, Gender DynamiX, SAMRC, UNISA and WHO. Chris McLachlan declares being the co-chair of WHO’s Guideline Development Group, advisory board member for Wits RHI – Transgender Clinics (2022–2025), secretary of the WPATH Board, board member of PATHSA (unpaid) and executive member of PsySSA Sexuality and Gender Division. Pierre Brouard declares receiving consulting fees from Centre for Sexualities, AIDS and Gender (CSA&G), Outright International, YALI Programme, and Centre for Human Rights, UP; travel support from Gender DynamiX, Outright International, CSA&G and Centre for Human Rights, UP. Pierre Brouard also declares PATHSA board membership (unpaid), and being an executive member of the Sexuality and Gender Division, PsySSA (unpaid). Landa Mabenge declares being expert witness in the case: Mokoena v Head of Johannesburg Correctional Centre: Medium B and Others (2024/070075) [2025] ZAEQC 7 (10 Nov 2025). Sakhile Msweli declares receiving an honorarium and travel support for training from Gender DynamiX, PsySSA African Human rights Project and SAMRC, and being a board member of PATHSA (unpaid). Liberty Matthyse declares that she is the executive director of Gender DynamiX, and board member of the International Trans Fund, and declares funding from the Co-Impact Gender Fund for just health systems strengthening work with Gender Dynamix. Marion Stevens declares receiving consultancy fees from Gender DynamiX, Triangle Project, SAMRC and the PEARLs study for Pre-Eclampsia at the Department of Gynaecology, University of Cape Town. Marion Stevens further declares having been a Consolidoc Fellow (Nov 2024 – Feb 2025), Department of Political Sciences, Stellenbosch University, and travel support to attend the 30th year anniversary of the Commission on Gender Equality and for meetings of the Gender Advisory Panel of the WHO (term completed 2024). Robin Dyers declares an NIHR Grant for research: PCAT in Southern Africa, receiving an honorarium and travel support for training from Gender DynamiX, travel support from Taiwan ICDF and WHO, being treasurer of the PATHSA board (unpaid), member of WHO FIC CC South Africa – MRCSA (unpaid) and board member of Project Flamingo (unpaid). Jenna-Lee de Beer-Procter declares being vice chair of the PATHSA board (unpaid), and co-chair of the WPATH International Outreach Committee (unpaid). Kevin Adams declares PATHSA board membership (unpaid). W.D. Francois Venter declares that his unit receives funding from the Bill and Melinda Gates Foundation, SAMRC, NIH, Unitaid, Foundation for Innovative New Diagnostics (FIND), Merck and the Children’s Investment Fund Foundation (CIFF), has previously received funding from USAID, and received drug donations from ViiV Healthcare, Merck, J&J and Gilead Sciences for investigator-led clinical studies. The unit does investigator-led studies with Merck, J&J, Gilead, and ViiV providing financial support and is doing commercial drug studies for Merck and Novo. The unit performs evaluations of diagnostic devices for multiple biotech companies. W.D. Francois Venter receives honoraria for educational talks and advisory board membership for Gilead, ViiV, Mylan/Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, J&J, Sanofi, Boehringer Ingelheim, Thermo-Fischer, and Virology Education. W.D. Francois Venter serves on the NIH International DSMB, and the board of Dira Sengwe (unpaid). Elma de Vries declares receiving an honorarium and travel support for training from Gender DynamiX, travel support from WHO for a Guideline Development Group Meeting in August 2024, serving as a member of the Wits RHI Technical Advisory Group–Transgender clinics (2022–2025), being board chairperson of PATHSA (unpaid), and a member of WPATH.

Ingrid Lynch: Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft, Writing – review & editing. KL Dunkle: Conceptualisation, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Writing – original draft, Writing – review & editing. Chris McLachlan: Conceptualisation, Writing – original draft, Writing – review & editing. Pierre Brouard: Conceptualisation, Writing – original draft, Writing – review & editing. Landa Mabenge: Writing – original draft, Writing – review & editing. Sakhile Msweli: Conceptualisation, Writing – original draft, Writing – review & editing. Liberty Matthyse: Conceptualisation, Funding acquisition, Writing – review & editing. Marion Stevens: Writing – original draft, Writing – review & editing. Robin Dyers: Conceptualisation, Data curation, Writing – review & editing. Jenna-Lee de Beer-Procter: Conceptualisation, Writing – original draft, Writing – review & editing. Kevin Adams: Writing – review & editing. W.D. Francois Venter: Conceptualisation, Writing – original draft, Writing – review & editing. Elma de Vries: Conceptualisation, Data curation, Writing – original draft, Writing – review & editing. All authors reviewed the article, contributed to the discussion of results, approved the final version for submission and publication, and take responsibility for the integrity of its findings.

This article followed all ethical standards for research without direct contact with human or animal subjects.

Ingrid Lynch, KL Dunkle, and Marion Stevens declare receiving consultancy fees for this project from Gender DynamiX. None of the other authors received remuneration for this work.

The authors confirm that the data supporting the findings of this study are available within the article and its references, and in the Online Supplementary Appendix file published with this article.

The views and opinions expressed in this article are those of the authors and are the product of professional research. They do not necessarily reflect the official policy or position of any affiliated institution, funder, agency, or that of the publisher. The authors are responsible for this article’s results, findings, and content.

References