Deciphering polycystic ovary syndrome: A brief overview from metabolic drivers to genetic and fetal origins

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine and metabolic disorder in women of reproductive age characterized by hormonal imbalances, menstrual irregularities, and changes in ovarian morphology. Excess body fat plays a significant role in the clinical development of PCOS. The complex relationship between adiposity and PCOS involves disruptions in hormonal balance and inflammatory processes, which both contribute to the clinical and phenotypic manifestations of the syndrome. Insulin resistance is a significant factor linking adiposity and PCOS. Moreover, reduced fertility is associated with adiposity in PCOS, with obesity exacerbating anovulation. Recent studies have raised questions about the role of androgen exposure during fetal life, including genetic factors related to PCOS identified in genome-wide association studies and Mendelian randomization studies. Managing PCOS should concentrate on addressing adiposity as a crucial target, positively impacting the syndrome, particularly regarding reproductive and fertility outcomes. This review aims to understand how metabolic conditions such as obesity and insulin resistance are linked to PCOS and how early prenatal androgen exposure is involved in its etiology. Particular attention is given to its role in developmental programming, fat distribution, and fat type, as well as how these factors contribute to the onset of metabolic disturbances in adulthood.