The Role of Estrogenic Mechanisms in Pathological Aggression: A Systematic Review of Preclinical and Clinical Trials

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Abstract
The high prevalence and economic burden of injuries and deaths related to violence and aggression invite the need to further assess the biological mechanisms underlying their expression. Evidence implicates estrogen signaling as a mediator of aggressive behavior. In accordance with PRISMA guidelines, a systematic search was performed using the following electronic databases: PubMed, Medline, Cochrane Library, PsycInfo, Embase, Scopus, and Web of Science. The databases were searched from inception to October 3, 2025. Study screening and selection were performed by three reviewers (A.K., L.C., and A.A.). The included studies reported on the role of estrogen in aggressive and antisocial behavior. A total of 103 studies were included in this review. Preclinical and clinical studies have consistently demonstrated the role of estrogen in social dominance and antagonistic behaviors. Early-life stress and anxiety can counteract these effects. Similarly, extant data suggest that aromatase, an enzyme that synthesizes estrogen from testosterone, is involved in reported aggression. This convergence between human and animal data supports the role of estrogen in instinctive behavior and invites future studies to assess the role of estrogen antagonism in aggressive behavior.

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