Emerging Therapeutic Targets in the Management of Polycystic Ovary Syndrome: Pathophysiological Insights

Abstract: Among all gynaecologic endocrinopathies, polycystic ovary syndrome (PCOS) is the most challenging condition to manage. It affects approximately 6–20% of women of reproductive age. The syndrome has a wide range of clinical presentations, including oligomenorrhea, recurrent abortions, disturbed follicular development, polycystic ovarian morphology, infertility, obesity, acne, alopecia, and hirsutism. Additionally, women with PCOS are more likely to develop endometrial carcinoma, metabolic disease, and cardiovascular disease. Disruptions in the highly regulated balance between hormonal and genetic factors are responsible for triggering polycystic ovaries and associated dysfunctions. Several molecular components, such as Sirtuin-1 (SIRT1), Chromobox Homolog 2 (CBX2), KISS1, and microRNAs, are pivotal in mediating hyperandrogenism and/or hyperinsulinemia, both of which are central to the pathogenesis of PCOS. Furthermore, elevated proinflammatory cytokines and their associated signalling mechanisms are increasingly recognized as contributing factors to disease pathogenesis. This review attempts to examine the hormonal, metabolic, inflammatory, genetic, and neuroendocrine pathways of PCOS to provide a more integrated perspective on the syndrome. Advancements in these areas can lead to the identification of novel therapeutic targets, thereby improving the management of PCOS and reducing long-term complications. Given the common occurrence of pathogenic factors in women with PCOS, early diagnosis and treatment are critical for minimizing disease-related morbidity and improving clinical outcomes.