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.