Adolescent Hormonal Contraceptive Use in the Context of Brain Development and Depression Risk: A Review and Considerations for Future Research.

Hormonal contraceptives (HCs) contain synthetic gonadal hormones that act on receptors widely distributed throughout the brain, thereby altering the body's endogenous hormonal milieu in ways that may influence brain and behavior. Although HCs are among the most commonly prescribed medications for female adolescents, their effects on the developing brain and mental health remain poorly understood. This gap is concerning given that adolescence is marked by substantial hormonal change, neurodevelopment, and a sharp rise in depression risk among female youth. In this review, we synthesize current evidence on associations between adolescent HC use, depression risk, and brain structure and function. Epidemiological studies have consistently reported associations between HC use during adolescence and increased depression risk, but causal interpretation is limited by residual confounding. Neuroimaging research remains scarce, particularly in adolescents, and rarely accounts for heterogeneity in HC formulations and characteristics of use or for endogenous hormonal variation related to puberty or the menstrual cycle. We outline 3 considerations to guide future research: accounting for HC heterogeneity, incorporating developmental features of adolescent menstrual cycles, and situating HC use within its broader developmental and sociocultural context. We conclude by emphasizing the need for rigorous developmentally sensitive research to counter misinformation and better support adolescents' reproductive and mental health care needs.