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Endocrine circuitry in autism spectrum disorders: A systematic review of mechanistic insights and clinical implications.

M. Angelopoulou,Panayiotis Siaperas,S. Livadas,Elina Karantana,Dimitrios T. Papadimitriou,Nicholas Angelopoulos

Published 2025 in Neuroscience

ABSTRACT

The increasing global prevalence of Autism Spectrum Disorder (ASD) diagnoses-largely driven by heightened awareness, evolving diagnostic criteria, and improved detection-has intensified efforts to elucidate its complex neurobiological underpinnings, although the true change in occurrence remains uncertain. While much attention has been paid to genetic and neurodevelopmental factors, emerging evidence highlights the crucial role of the endocrine system in modulating social, cognitive, and behavioral outcomes associated with ASD. To systematically review the existing literature on endocrine dysfunction and hormonal signaling pathways implicated in ASD, with the aim of identifying common mechanistic links and evaluating their clinical relevance.A comprehensive literature search was conducted across PubMed, Scopus, and Google Scholar for studies published between 1980 and 2024. The review included 183 human studies evaluating associations between ASD and hormonal alterations, encompassing thyroid function, HPA axis dysregulation, growth hormone signaling, sex hormones, obesity, melatonin, oxytocin, vitamin D status, and exposure to endocrine-disrupting chemicals. Alterations in multiple endocrine axes were consistently associated with ASD, including prenatal thyroid imbalances, cortisol rhythm dysregulation, aberrant IGF-1 levels, elevated fetal steroidogenic activity, and impaired oxytocin signaling. Endocrine disruptors such as phthalates and pesticides were also linked to increased ASD risk in susceptible populations. Endocrine dysfunctions are frequently associated with ASD, with multiple hormonal axes potentially influencing its pathophysiology, although causality remains unconfirmed. Understanding hormonal influences across developmental stages could inform early detection strategies and novel therapeutic approaches.

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