PCOS and peptides — what the literature actually supports for polycystic ovary syndrome across the GLP-1, amylin, and HPG-axis classes

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women — the World Health Organization estimates a prevalence of 8–13% globally, with Global Burden of Disease 2021 reporting a ~28–30% rise between 1990 and 2021. The clinical condition is heterogeneous by design. Since the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Fertil Steril 2004, 81:19–25 revised the diagnostic criteria, PCOS has been defined as any two of three features — oligo-anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound — and the resulting Phenotype A through Phenotype D split is what the modern PCOS literature is organized around. Phenotype A carries all three features and is most tightly coupled to the obesity–insulin-resistance axis. Phenotype D (polycystic morphology plus anovulation, no hyperandrogenism) is the most contested category and the one whose pharmacological case is weakest.

The editorial center of this dossier is the GLP-1 receptor agonist class. Insulin resistance is a near-universal feature of obesity-associated PCOS and a frequent feature even in lean PCOS, so any incretin or insulin-sensitizing pharmacology hits the substrate that drives the reproductive and metabolic phenotypes. The 2023 international evidence-based guideline (Teede et al., J Clin Endocrinol Metab 2023, 108:2447–2469) addresses anti-obesity pharmacotherapy as a consideration in PCOS — GLP-1 RAs may be considered "based on general population guidelines, balancing potential benefits and side effects" — while noting that no anti-obesity medication is approved specifically for PCOS. The supporting systematic review (Goldberg et al., Obes Rev 2024, 25:e13704; 11 RCTs, 996 participants) reported liraglutide and semaglutide as superior to placebo for anthropometric outcomes in PCOS while concluding that "published data examining the effects of anti-obesity agents in women with PCOS are very limited." That gap between mechanistic case and trial scaffolding is the load-bearing fact this dossier exists to make legible.

This is a survey of peptide pharmacology across PCOS, not a treatment guide. The framing throughout is informational. Hyperandrogenism management (anti-androgen pharmacology, oral contraceptives, mechanical hair removal) is non-peptide and outside scope; the female sexual dysfunction dossier and andropause dossier cover adjacent sex-axis pharmacology.