Does including multiple hormones and family context together clarify hormone-behavior associations? A systematic review.

The objective of this study was to review the literature to determine whether simultaneously considering the hormonal milieu and the parenting domain of family context clarifies hormone-behavior associations in children and adolescents. We conducted a systematic review of PubMed, Scopus, and Web of Science in May 2024 and PsycINFO in May 2025. Inclusion criteria: Studies included variable(s) assessing family context in the parenting domain, measures of multiple hormones in children/adolescents where at least one was from the hypothalamic-pituitary-adrenal (HPA) or hypothalamic-pituitary-gonadal (HPG) axis, and a child/adolescent behavioral outcome, and children/adolescents studied were under 18 years. Reviews and animal studies, studies that were not peer reviewed (e.g., dissertation/theses, chapters) or not written in English were excluded. Our search and screen yielded 27 articles. The Robins-E tool was used to assess risk of bias; we provide a narrative synthesis of results. Most studies examined multiple hormones, but independently. Fewer studies included measures of hormonal milieu, using ratios most often, but also data aggregation (e.g., factors, profiles), and/or by calculating interactions among hormones. Childhood maltreatment was the family context construct most often assessed, followed by parent psychopathology, and less often, measures of parent-child relationship quality. Results provided some evidence that 1) hormonal milieu-behavior associations differ in the context of family conflict than social evaluative threat. 2) Less positive family environments were associated with high cortisol-to-(low) DHEA ratios cross-sectionally, but to lower cortisol-to-DHEA ratio longitudinally, and cortisol-to-DHEA ratios can be associated with behavior problems, though inconsistently across studies. And, 3) maltreatment can strengthen single hormone-behavior associations but may not moderate the association of hormonal milieu with behavioral outcomes. There was a surprising lack of longitudinal studies, and very few replication opportunities across specific findings given the heterogeneity in which phenotypes were measured and the construction of models. We provide recommendations for future research including a framework for future work to build a more systematic literature base regarding the role of family context in multihormone-behavior associations.