Interventions for Transgender and Gender-Expansive Youth

Gender-affirming interventions aim to treat gender dysphoria, the clinically significant distress and impairment that can result from inconsistency between one's gender identity and sex-related characteristics. Transgender and gender-expansive (TGE) individuals may experience gender dysphoria, but not all TGE people need or seek treatment.^[1]

Practitioners have set clinical practice standards of care for TGE people that guide how to address gender dysphoria across the lifespan. The relevant professional societies regularly update these standards based on the best available research evidence, professional expertise, and patient perspectives (Coleman et al., 2022; Hembree et al., 2017).

Yet there are varying opinions regarding which, if any, gender-affirming interventions should be available to TGE minors and young adults, whose gender identities may still be developing. Policymakers in dozens of states have proposed or enacted laws that restrict or ban gender-affirming care; laws in other states promote access to this care. Legal challenges to Tennessee's ban resulted in an active U.S. Supreme Court case, United States v. Skrmetti.

Reviewing the Evidence

To inform decisionmaking, a team of researchers from RAND and Indiana University conducted a systematic review in which they identified and summarized peer-reviewed studies on a variety of health outcomes from interventions for gender dysphoria delivered to TGE youth (age 25 and younger). The researchers used a suite of critical appraisal checklists to assess how well each study addressed statistical bias in its design and analysis. The researchers also assessed the evidence for each intervention outcome using certainty-of-evidence criteria from GRADE (Grading of Recommendations Assessment, Development and Evaluation),^[2] the most widely used framework for summarizing research evidence to inform health practice and policy (Guyatt et al., 2008, 2011).

What the Evidence Says

The review offers an up-to-date summary of evidence (through 2023) from 105 studies. Figure 1 uses bars to summarize the evidence, categorized by interventions (rows) and outcomes (columns). The bar colors indicate evidence of benefits (purple), evidence of harms (yellow), and lack of clinically significant effects (gray). The team found evidence for five intervention categories that are from the standards of care (psychosocial interventions, puberty-suppressing hormones, hormone replacement therapy, gender-affirming surgeries, and reproductive health interventions). No relevant evidence for outcomes in youth was found for voice therapy or support for detransition. The team also found evidence for two categories of alternative interventions (treatment of co-occurring disorders and gender identity and expression change efforts [GIECE], the latter sometimes called conversion therapy or reparative therapy). GRADE certainty-of-evidence ratings were categorized as very low (a diamond or dot pattern on the bar) for 89 percent of outcomes and low (a solid bar) for 11 percent.

Overall, the identified benefits and potential harms across intervention categories, as well as the assessment of the high risk of statistical bias in this body of evidence, were consistent with the results of previous reviews that summarized the research evidence for specific interventions related to gender dysphoria in TGE youth. The full report provides a list of these reviews.

Intervention categories that have beneficial effects on outcomes

Psychosocial interventions: Social transition

• Mental Health
  • Suicidality: 5 studies, very low level of certainty
  • Depression or mood: 6 studies, very low level of certainty
  • Other symptoms: 7 studies, very low level of certainty

Psychosocial interventions: Other

• Mental Health
  • (Peer groups): 4 studies, very low level of certainty
  • Family support (Family or caregiver therapy): 2 studies, very low level of certainty
  • Suicidality (Coping-oriented videos): 1 study, very low level of certainty

Puberty-suppressing hormones

• Gender dysphoria: 11 studies, very low level of certainty
• Pubertal changes targeted for suppression: 20 studies, low level of certainty
• Mental health: 21 studies, very low level of certainty

Hormone replacement therapy

• Gender dysphoria: 8 studies, very low level of certainty
• Pubertal changes targeted for initiation: 14 studies, low level of certainty
• Mental health: 21 studies, very low level of certainty
• Bone health: 7 studies, very low level of certainty

Gender-affirming surgeries

• Gender dysphoria
  • Mastectomy: 10 studies, low level of certainty
  • (Other surgeries [a]): 4 studies, very low level of certainty
  • (Other surgeries [b]): 5 studies, very low level of certainty
• Mental health:10 studies, very low level of certainty

Reproductive health interventions

• Fertility
  • Oocyte or embryo cryopreservation: 7 studies, very low level of certainty
  • Semen cryopreservation: 2 studies, very low level of certainty

Intervention categories that have no clinically significant effects on outcomes

Psychosocial interventions: Social transition

• Regret or dissatisfaction: 3 studies, very low level of certainty

Psychosocial interventions: Other

• Mental Health (treatment as a precondition): 2 studies, very low level of certainty

Puberty-suppressing hormones

• Regret or dissatisfaction: 14 studies, very low level of certainty
• Side effects or complications: 18 studies, very low level of certainty
• Fertility: 2 studies, very low level of certainty, case studies only

Hormone replacement therapy

• Regret or dissatisfaction: 13 studies, very low level of certainty
• Side effects or complications: 19 studies, very low level of certainty
• Fertility: 7 studies, very low level of certainty

Gender-affirming surgeries

• Regret or dissatisfaction: 9 studies, very low level of certainty
• Side effects or complications: 10 studies, very low level of certainty

Treatment of co-occurring disorders

• Gender dysphoria co-occurring with autism spectrum disorder: 2 studies, very low level of certainty, case studies only
• Mental health
  • Eating disorder symptoms: 3 studies, very low level of certainty, case studies only
  • Depression of anxiety: 3 studies, very low level of certainty, case studies only

Intervention categories that have harmful effects on outcomes

Puberty-suppressing hormones

• Bone health: 10 studies, very low level of certainty

Gender identity and expression change efforts

• Mental health
  • Suicidality: 3 studies, low level of certainty
  • Other symptoms: 2 studies, very low level of certainty

NOTE: Full details of all outcomes are available in the corresponding report. Bars represent the number of studies with evidence for each intervention and outcome. When needed for clarity, labels next to bars specify outcome categories outside parentheses, and intervention categories are in parentheses.
^a Hysterectomy/ovariectomy and/or metoidioplasty or phalloplasty.
^b Vaginoplasty and/or mammaplasty.

Implications for Policy, Practice, and Research

The findings from this review pose a challenge for practitioners and policymakers seeking to make decisions that incorporate the best available evidence. Notably, the RAND report differed from the widely reported Cass Review (2024), which was guided by its mandate to make UK National Health Service policy recommendations regarding services provided to TGE youth. In contrast, the RAND–Indiana University team sought to provide evidence summaries for broad use across multiple contexts.

Practice

The GRADE Evidence to Decision framework can be used to balance the limited certainty of the evidence found in this review with other key considerations when developing or updating standards of care for youth with gender dysphoria to incorporate the best available science. Interventions with low or very low certainty of evidence can be considered for use in clinical practice with appropriate considerations, although guideline panels might not want to make recommendations for some interventions, populations, or outcomes because of insufficient evidence. GRADE guidance especially encourages panels to consider making recommendations when providing no recommendation would be unhelpful to providers or could harm patients.

Policy

Evidence-informed approaches that account for uncertainty are available to policymakers as they consider legislative and policy decisions that affect health outcomes. Such approaches (Dumont, 2019; U.S. Government Accountability Office, 2023; World Health Organization, 2021) can help policymakers incorporate the evidence summarized in this review into policies that address major risks of harm to TGE youth, whether from the provision or restriction of interventions.

Research

Researchers can use these findings to guide future studies that produce higher-certainty evidence about interventions for TGE youth. However, more supports are needed for conducting rigorous research on this topic. Implications for researchers are discussed at length in the report.

Notes

• [1] Gender expansive includes nonbinary and other identities outside male or female.
• [2] Certainty of evidence is the level of confidence—from very low to high—that an intervention’s estimated effect on an outcome (from systematically reviewed research) represents the actual effects.

References

• Cass Review, Independent Review of Gender Identity Services for Children and Young People: Final Report, April 2024.
• Coleman, Eli, Asa E. Radix, Walter P. Bouman, George R. Brown, Annelou L. C. de Vries, Madeline B. Deutsch, R. Ettner, L. Fraser, M. Goodman, J. Green, et al., "Standards of Care for the Health of Transgender and Gender Diverse People, Version 8," International Journal of Transgender Health, Vol. 23, Supp. 1, 2022.
• Dumont, Kimberly, Reframing Evidence-Based Policy to Align with the Evidence, William T. Grant Foundation, 2019.
• Guyatt, Gordon, Andrew D. Oxman, Elie A. Akl, Regina Kunz, Gunn Vist, Jan Brozek, Susan Norris, Yngve Falck-Ytter, Paul Glasziou, Hans DeBeer, et al., "GRADE Guidelines: 1. Introduction—GRADE Evidence Profiles and Summary of Findings Tables," Journal of Clinical Epidemiology, Vol. 64, No. 4, April 2011.
• Guyatt, Gordon H., Andrew D. Oxman, Gunn E. Vist, Regina Kunz, Yngve Falck-Ytter, Pablo Alonso-Coello, and Holger J. Schünemann, "GRADE: An Emerging Consensus on Rating Quality of Evidence and Strength of Recommendations," BMJ, Vol. 336, No. 7650, April 2008.
• Hembree, Wylie C., Peggy T. Cohen-Kettenis, Louis Gooren, Sabine E. Hannema, Walter J. Meyer, M. Hassan Murad, Stephen M. Rosenthal, Joshua D. Safer, Vin Tangpricha, and Guy G. T’Sjoen, "Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline," Journal of Clinical Endocrinology & Metabolism, Vol. 102, No. 11, November 2017.
• U.S. Government Accountability Office, Evidence-Based Policymaking: Practices to Help Manage and Assess the Results of Federal Efforts, July 2023.
• World Health Organization, Evidence, Policy, Impact: WHO Guide for Evidence-Informed Decision-Making, 2021.

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Topics

• Adolescent Health
• Evidence Based Health Practice
• Health Interventions
• LGBTQ+ Populations
• Mental Health Treatment
• Pediatric Medicine