Targeting adipokines in polycystic ovary syndrome and related metabolic disorders: from experimental insights to clinical studies

Polycystic ovary syndrome (PCOS) affects approximately 15% of women of reproductive age worldwide. It is the most prevalent endocrine disorder with marked risks for female infertility, type 2 diabetes mellitus (T2DM), psychiatric disorders and gynecological cancers. Although the pathophysiology of PCOS remains largely elusive, growing evidence suggests a close link with obesity and its related metabolic disorders. As a highly active endocrine cell population, hypertrophic adipocytes in obesity have disturbed production of a vast array of adipokines, biologically active peptides that exert pleiotropic effects on homeostatic regulation of glucose and lipid metabolism. In parallel with their crucial roles in the pathophysiology of obesity-induced metabolic diseases, adipokines have recently been identified as promising targets for novel therapeutic strategies for multiple diseases. Current treatments for PCOS are suboptimal with insufficient alleviation of all symptoms. Novel findings in adipokine-targeted agents may provide important insight into the development of new drugs for PCOS. This Review presents an overview of the current understanding of mechanisms that link PCOS to obesity and highlights emerging evidence of adipose-ovary crosstalk as a pivotal mediator of PCOS pathogenesis. We summarize recent findings of preclinical and clinical studies that reveal the therapeutic potential of adipokine-targeted novel approaches to PCOS and its related metabolic disorders. We also discuss the critical gaps in knowledge that need to be addressed to guide the development of adipokine-based novel therapies for PCOS.