Disrupted rhythms and dysfunction: A chronobiological perspective on polycystic ovary syndrome

Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine-metabolic disorder characterized by reproductive irregularities, hyperandrogenism, and insulin resistance. Recent advances in chronobiology have introduced a compelling narrative suggesting that dysregulation in circadian system is a contributing factor in the pathogenesis and clinical manifestation of PCOS. This review explores how disrupted biological timing—reflected in misaligned central and peripheral clocks, altered melatonin dynamics, and irregular sleep-wake cycles—intersects with metabolic and hormonal dysfunctions in PCOS. We highlight emerging evidence linking aberrant expression of clock genes such as CLOCK, BMAL1, and PER1 in ovarian, hepatic, and hypothalamic tissues to ovulatory failure, insulin resistance, and androgen excess. Moreover, melatonin, a key circadian hormone, demonstrates altered systemic and follicular profiles in PCOS, influencing folliculogenesis, oxidative stress, and steroidogenesis. Further, this review delves into the neuroendocrine pathways by which circadian cues modulate the hypothalamic-pituitary-ovarian axis and how their disruption may contribute to reproductive impairment. In light of these findings, we discuss chronotherapeutic approaches—including melatonin supplementation, time-restricted feeding, light therapy, and circadian-timed pharmacotherapy—as emerging strategies for personalized and temporally aligned PCOS treatment. Despite limitations in clinical standardization and the need for biomarker-based stratification, chronomedicine offers a promising adjunct to traditional PCOS management. By framing PCOS as a disorder of temporal dysregulation, this review advocates for a paradigm shift in both understanding and treating the syndrome, paving the way toward circadian-informed clinical care.