Randomized-controlled trials are methodologically inappropriate in adolescent transgender healthcare

Abstract

Background: Despite multiple rigorous observational studies documenting the association between positive mental health outcomes and access to puberty blockers, hormone therapy, and transition-related surgeries among adolescents, some jurisdictions have banned or are attempting to ban gender-affirming medical interventions for minors due to an absence of randomized-controlled trials (RCTs) proving their mental health benefits. Methods: This article critically reviews whether RCTs are methodologically appropriate for studying the association between adolescent gender-affirming care and mental health outcomes. Results: The scientific value of RCTs is severely impeded when studying the impact of gender-affirming care on the mental health of trans adolescent. Gender-affirming interventions have physiologically evident effects and are highly desired by participants, giving rise to concerns over adherence, drop-out, response bias, and generalizability. Complementary and well-designed observational studies can instead be used to ground reliable recommendations for clinical practice and policymaking in adolescent trans healthcare, without the need for RCTs. Conclusion: The lack of RCTs on the mental health impacts of gender-affirming care for trans adolescents does not entail that gender-affirming interventions are based on insufficient evidence. Given the methodological limitations of RCTs, complementary and well-designed observational studies offer more reliable scientific evidence than RCTs and should be considered of sufficient quality to guide clinical practice and policymaking.