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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月29日

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

摘要

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.