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

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-Müllerian 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-Müllerian 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.

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Publication Details

Journal
Nature Medicine
Published
2025-10-29
DOI
https://doi.org/10.1038/s41591-025-03984-1
Citations
4
Primary Topic
Ovarian function and disorders
Type
article
Field-Weighted Citation Impact
6.79

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article

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

Honghui Zhang, Betânia Rodrigues dos Santos, Shigang Zhao, Yuhua Shi et al.
4 citations
Nature Medicine
Ovarian function and disorders
6.79
article

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

Honghui Zhang, Betânia Rodrigues dos Santos, Shigang Zhao, Yuhua Shi, Qiang Wang, Junhao Yan, Jingpeng Liu, Yonghui Jiang, Ziyi Yang, Linlin Cui, Mingfeng Xia, Eu‐Leong Yong, Yu Tian, Yuqing Zhang, Xueying Gao, Junli Zhao, Elisabet Stener‐Victorin, Poli Mara Spritzer, Richard S. Legro, Bülent Okan Yıldız, Yuli Qian, Han Zhao, Xiang‐Hong Ou, Ye Tian, Daimin Wei, Yanzhi Du, Yuehong Bian, Lingxia Ha, Yue Liu, Xin Zhang, Lin Zhou, Xin Liu, Shumin Li, Yingying Qin, Yue Zhao, Jingjie Li, Jun Ma, Shixuan Wang, Rong Tang, Heping Zhang, Xiang Ma, Yun Sun, Yanping Li, Chuanxin Zhang, Shuai Zhao, Zhuowei Gu, Jingyu Li, Feng He, Xiaoyan Liang, Shanshan Gao, Hui Zhao, Jingmei Hu, Zi‐Jiang Chen, Lingling Ding, Xi Yuan, Xueru Song, Na Li
article en
4 citations

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-Müllerian 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-Müllerian 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.

Nature MedicineVol. 31(12)
Zhejiang International Studies University (CN), Universidade Federal do Rio Grande do Sul (BR), Central South University (CN), Shandong University (CN), Sun Yat-sen University (CN), Jinan University (CN), National University of Singapore (SG), Shanghai Jiao Tong University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Fudan University (CN), Renji Hospital (CN), Tianjin Medical University General Hospital (CN), Karolinska Institutet (SE), Yale University (US), Chengdu Women's and Children's Central Hospital (CN), Sixth Affiliated Hospital of Sun Yat-sen University (CN), Hospital de Clínicas de Porto Alegre (BR), Second Hospital of Shandong University (CN), Shandong Provincial Hospital (CN), Zhongshan Hospital (CN), Ningxia Medical University (CN), The First Affiliated Hospital, Sun Yat-sen University (CN), Women's Hospital, School of Medicine, Zhejiang University (CN), Institut de Médecine de la Reproduction (FR), Peking University Third Hospital (CN), National University Hospital (SG), Shandong Maternal and Child Health Hospital (CN), Xiangya Hospital Central South University (CN), Tongji Hospital (CN), Qilu Hospital of Shandong University (CN), Shandong First Medical University (CN), Shandong Academy of Chinese Medicine (CN), State Key Laboratory of Reproductive Medicine, Huazhong University of Science and Technology (CN), Hacettepe University (TR), Penn State Milton S. Hershey Medical Center (US), Nanjing Medical University (CN)
Shandong University, National Natural Science Foundation of China, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Novo Nordisk, Shanghai Jiao Tong University, Natural Science Foundation of Shandong Province, University of Science and Technology of China, Novo Nordisk Fonden, National Institutes of Health, School of Medicine, University of Alabama at Birmingham, Medical Research Council, School of Medicine, Shanghai Jiao Tong University, National Key Research and Development Program of China, School of Life Sciences and Biotechnology Division of Life Sciences, Korea University
Openalex Percentile: Top 3%
Ovarian function and disorders
6.79
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