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Melatonin as a protector against endocrine disruption across tissues: A systematic review
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A systematic review of 61 studies, from 2000 to 2025, of melatonin and the toxicity of endocrine-disrupting chemicals, including bisphenols, phthalates, heavy metals, pesticides and microplastics. The studies were in humans, mammals or cell models, and melatonin was associated with less toxicity across several tissues.
Endocrine-disrupting chemicals (EDCs) are widespread environmental pollutants that interfere with hormonal homeostasis and contribute to multisystem toxicity. This systematic review aimed to synthesize available evidence on the protective effect of melatonin against EDC-induced toxicity across tissues. English language articles published between January 2000 and December 2025 were searched on PubMed, Web of Science, and Wiley Online. Eligible studies evaluated the protective or antagonistic effects of melatonin against EDC-induced toxicity in humans, mammals, or in vitro models. Data on study characteristics, EDC exposure, melatonin intervention, affected tissues, outcomes, and mechanisms were extracted, synthesized, and reported in accordance with the PRISMA 2020 guidelines. Sixty-one studies met the inclusion criteria. Melatonin exhibited protective effects against diverse EDCs, including bisphenols, phthalates, heavy metals, pesticides, and microplastics. The principal mechanisms identified were antioxidant and free-radical scavenging activity, modulation of hormone receptors, regulation of gene and protein expression, stabilization of endocrine axes, mitochondrial protection, and epigenetic modulation. These effects were observed across multiple organ systems, particularly the reproductive, neuroendocrine, cardiovascular, adrenal, and immune systems. Melatonin protects against EDC-induced multisystem toxicities by preserving endocrine signaling and coordinating cellular defense mechanisms across tissues, thereby holding therapeutic potential.
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This review covers how micro- and nanoplastics and additives such as phthalates cause oxidative stress and inflammation in cells. It then discusses melatonin, a hormone and antioxidant, as one candidate for countering that damage. The authors note that methods tried so far have not been entirely successful.
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Male rats were given polyethylene microplastics at two doses, with or without melatonin. The study is the first to look at the adrenal gland, and it found toxic effects there. Rats that also received melatonin showed less adrenal damage.
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Researchers found that polyethylene microplastics damaged the intestinal barrier in rats by causing inflammation, reducing protective mucus, and disrupting the tight junctions between gut cells. The damage was more severe at higher doses and included changes in gut bacteria composition. The study also found that melatonin treatment helped protect against these intestinal effects, suggesting potential avenues for reducing microplastic-related gut damage.
Protective effects of melatonin against polystyrene nanoplastic–induced placental dysfunction and adverse pregnancy outcomes in rats
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In pregnant rats, exposure to nanoplastics (tiny plastic particles found in everyday pollution) damaged the placenta and harmed pregnancy outcomes by increasing cell-damaging stress. Melatonin, a hormone your body makes naturally (and that's sold as a sleep supplement), helped protect against this damage when given to the rats. While this is early animal research and hasn't been tested in humans yet, it raises hopeful questions about whether melatonin could someday help protect pregnancies from the growing problem of plastic pollution in our environment.
Melatonin Modulates Bisphenol S Induced Alterations in Metabolic Status and Ovarian Functions in Adult Golden Hamster, Mesocricetus auratus
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In adult female golden hamsters, bisphenol S, a common substitute for BPA, altered blood lipids, enlarged fat cells and disrupted ovarian function. Hamsters that also received melatonin had lipid profiles closer to normal.
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