biostudies-literatureGao XNCATS NIH HHSNICHD NIH HHSNCCIH NIH HHSNHLBI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)National Natural Science Foundation of China (National Science Foundation of China)4214-4224https://www.ebi.ac.uk/biostudies/studies/S-EPMC12705455biostudies-literatureUnknown31(12)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 complicNature medicineData-driven subtypes of polycystic ovary syndrome and their association with clinical outcomes.PMC12705455R01AT009484-A1UL1 TR00201432370916R01 HD09135032588201R01 HD091350-04R01 HD100630R01 AT009484821017071R01HD1006301R43HD11427-01UG3/UH3 HL162971UG3 HL162971Liang XZhang HDu YShi YWang QXia MWang SBian YYuan XZhang CYildiz BOHe FLi JHa LSun YChina Women’s Reproductive Metabolic NetworkLi XYang ZLi YLi SHu JGao XLegro RSGao SLiu JOu XHMa XQin YYong ELDing LZhao YLiu XJiang YLiu YZhao STang RChen ZJSong XZhao JZhao HZhou LYan JCui LWei DSantos BRGu ZQian YZhang YTian YSpritzer PMStener-Victorin EZhang XMa JfalseData-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 complic2025-01-01T00:00:00Z2025 Dec2026-06-06T04:02:00.918Z2026-05-25T03:12:06.77ZS-EPMC127054554116265210.1038/s41591-025-03984-1