Environmental toxins and toxic metals in autoimmune diseases: Sex differences, hormonal influences, and immune dysregulation

Environmental toxins, including toxic metal(oid)s such as mercury, lead, cadmium, and arsenic, as well as endocrine-disrupting chemicals like bisphenol A and phthalates, play a critical role in the onset and progression of autoimmune diseases. These substances accumulate in biological tissues and disrupt immune homeostasis through oxidative stress, molecular mimicry, and epigenetic modifications, mechanisms that contribute to autoantibody production and chronic inflammation, hallmarks of autoimmunity. Women are disproportionately affected by autoimmune diseases due to inherent differences in immune function, hormonal regulation, and genetic susceptibility. Estrogen, a key immunomodulatory hormone, can amplify immune responses and promote autoantibody generation. Its interaction with environmental toxins further exacerbates immune dysregulation, increasing female vulnerability to conditions such as systemic lupus erythematosus, rheumatoid arthritis, and autoimmune thyroid disorders. Hormonal fluctuations during puberty, pregnancy, and menopause additionally influence toxin metabolism and detoxification efficiency, compounding the risk of immune imbalance and disease onset in women. This review synthesizes current evidence on the mechanisms through which environmental toxicants contribute to autoimmune pathogenesis, with particular focus on sex-specific vulnerabilities. It explores the role of hormonal-immune-environment interactions across the female lifespan and highlights emerging research on epigenetic inheritance, gut dysbiosis, and biomarker development. By integrating mechanistic, epidemiological, and clinical findings, this review aims to inform targeted strategies for prevention, early detection, and risk reduction of environmentally driven autoimmune diseases.