Data-driven subtypes of polycystic ovary syndrome and their association with clinical outcomes


Gao X., Zhao S., Du Y., Yang Z., Tian Y., Zhao J., ...More

NATURE MEDICINE, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2025
  • Doi Number: 10.1038/s41591-025-03984-1
  • Journal Name: NATURE MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Nature Index
  • Hacettepe University Affiliated: Yes

Abstract

Polycystic ovary syndrome (PCOS) is a common and heterogeneous endocrine disorder that affects 11%-13% of women worldwide, with profound implications for fertility and long-term metabolic health. Here we identify four reproducible subtypes-PCOS with hyperandrogen, with obesity, with high-sex hormone-binding globulin and with high-luteinizing hormone-anti-M & uuml;llerian hormone-through unsupervised clustering of 9 clinical variables in 11,908 affected women, validated across 5 international cohorts. Prospective 6.5-year follow-up and in vitro fertilization treatment data revealed distinct reproductive and metabolic trajectories: hyperandrogenic PCOS showed the highest risk of second trimester pregnancy loss and dyslipidemia incidence; PCOS with obesity exhibited the most severe metabolic complications, lowest live birth rates and highest PCOS remission rate; PCOS with high-sex hormone-binding globulin demonstrated favorable reproductive outcomes and the lowest incidence of diabetes and hypertension; and PCOS with high-luteinizing hormone-anti-M & uuml;llerian hormone had the greatest risk of ovarian hyperstimulation and the lowest PCOS remission rate. These findings advance understanding of PCOS heterogeneity and provide a framework for subtype-based risk stratification and personalized management.