Non-chemical, chemical, and biochemical, endocrine disruptors: biphasic health effects and pathophysiological insights

Endocrine-disrupting chemicals (EDCs) interfere with hormone synthesis, signaling, and metabolism, leading to reproductive, metabolic, and neuroendocrine dysfunction. Non-chemical environmental endocrine stressors, including electromagnetic fields, noise, artificial light at night, and thermal stress, can disrupt endocrine homeostasis, alter neuroendocrine and hormonal function, affect signaling pathways, oxidative stress responses, and circadian rhythms. Unlike classical EDCs, which primarily exert their effects by direct binding to hormone receptors and metabolic enzymes, non-chemical endocrine disruptors predominantly act through central regulation of hypothalamic-pituitary-organ axes. EDCs, especially their biochemically active secondary metabolites, disrupt endocrine homeostasis by directly binding target hormone receptors or enzymes and then interacting with the hypothalamus-pituitary-organ axes. These physical stressors modulate molecular pathways, including MAPK and NF-κB signaling, oxidative stress responses, and circadian rhythm regulation, thereby affecting reproductive and neuroendocrine functions. Their physiological and biochemical effects depend on exposure intensity, duration, and timing; these effects vary according to sex and species. Non-chemical or biochemical endocrine disruptors may exhibit adverse or beneficial effects, depending on exposure conditions, and can modulate major endocrine hormones and inflammatory mediators, supporting their therapeutic applications. Music therapy, cryotherapy, thermotherapy, phototherapy, and pulsed electromagnetic field therapies are used to reduce inflammation, enhance circulation, facilitate musculoskeletal recovery, treat neonatal jaundice, and manage diverse clinical conditions. This review aims to explain non-chemical environmental disruptors, their partially overlapping mechanisms that target the same hormonal, circadian, and cellular signaling pathways, and to discuss their potential therapeutic applications.