Journal Article

Precision Targeted Therapy for PCOS: Emerging Drugs, Translational Challenges, and Future Opportunities

Yi, Wei, Wu, Xinhong, Liu, Xiawen

2026

Overview

Polycystic Ovary Syndrome (PCOS) is characterized by a self-perpetuating vicious cycle between insulin resistance (IR) and hyperandrogenism (HA). While lifestyle management remains the internationally recommended first-line treatment, current clinical management, primarily relying on combined oral contraceptives and metformin, offers symptomatic relief or “masking” of the phenotype but fails to adequately disrupt this core pathophysiological loop, while also carrying potential intergenerational safety concerns. This review systematically evaluates the paradigm shift toward mechanism-based precision medicine. First, we analyze emerging precision-targeted therapies that intervene in specific pathological nodes: (1) metabolic regulators (e.g., GLP-1RAs, SGLT2i, and brown adipose tissue (BAT) activators) that target systemic glucotoxicity and the novel “BAT-Ovarian axis”; (2) neuroendocrine modulators (e.g., NK3R antagonists) that act as negative modulators of the hyperactive GnRH pulse generator; and (3) innovative androgen synthesis inhibitors (e.g., Artemisinins) that utilize a degradation-at-source mechanism. Complementing these, we explore the strategic value of Natural Products through the lens of “Network Pharmacology”, highlighting their ability to restore systemic homeostasis via multi-target modulation. Finally, we address critical translational challenges, specifically the need to establish long-term reproductive and offspring safety, providing a roadmap for developing true disease-modifying treatments for PCOS. Distinct from reviews limited to isolated therapeutic modalities, this article uniquely bridges current clinical management with emerging organ-specific precision targets and natural product networks.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Adipose tissue (brown) / Drug development / Drug therapy / Forecasts and trends / Gonadotropin-releasing hormone / Health aspects / Homeostasis / hyperandrogenism (HA) / Infertility / Insulin resistance / insulin resistance (IR) / Metformin / Molecular targeted therapy / Natural products / network pharmacology / Neuromodulation / Obesity / Oral contraceptives / Phenotypes / Polycystic ovary syndrome / polycystic ovary syndrome (PCOS) / Precision medicine / Review / Stein-Leventhal syndrome / Testing / Thromboembolism / Translation