Polycystic ovary syndrome and the circadian clock: Understanding the link between metabolism, hormones, and sleep

Abstract

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with significant metabolic, reproductive, and psychological effects. Emerging research indicates that the disruption of circadian rhythm significantly contributes to the onset and progression of PCOS, a feature that has been insufficiently addressed. This paper presents a distinctive and comprehensive exploration of how circadian discordance, through clock gene dysregulation, sleep-wake disturbances, and external factors such as shift work, contributes to the pathophysiology of the polygenic disorder known as PCOS. This review is distinctive in that it offers opportunities to synthesize knowledge in the molecular biology of insulin processes, endocrinology, and behavioral sciences concerning circadian rhythms, insulin sensitivity, glucose metabolism, regulation of reproductive hormones, and mental health outcomes, in contrast to the prior literature. The article is organized into sections that address the molecular basis of circadian imbalance, its impact on the hypothalamic-pituitary-ovarian (HPO) axis, and its psychological implications, including persistent mood disorders and cognitive impairments. Furthermore, it introduces the novel potential of chronotherapy and circadian-based lifestyle modifications as systemic therapeutic alternatives. This review advances the understanding of circadian biology in PCOS by integrating a multidisciplinary body of knowledge, addressing research gaps, and proposing a new avenue of investigation into therapeutic strategies focused on circadian alignment to improve patient outcomes in PCOS.