ArticleNature medicine2025
Data-driven subtypes of polycystic ovary syndrome and their association with clinical outcomes.
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Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 4 of them syntheses that pooled it.
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22citing papers in PubMed, 4 pooled it
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Who cites it
22 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Metabolic profiling of human follicular fluid to unravel the pathways involved in polycystic ovary syndrome - a systematic review.Reviews in endocrine & metabolic disorders · 2026Pooled it
- Association between serum complement C3 and polycystic ovary syndrome: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Effects of acupuncture-related therapies on endocrine and metabolic outcomes in obese women with polycystic ovary syndrome: a systematic review and network meta-analysis.Frontiers in medicine · 2026Pooled it
- Traditional herbal medicine for obesity-related polycystic ovary syndrome: a meta-analysis and data mining study.Frontiers in pharmacology · 2025Pooled it
- MASLD, diabetes and PMOS across the female life stages.Diabetologia · 2026Review
- From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.Stem cell reviews and reports · 2026Review
- A Biological Disease-Staging Model of Polyendocrine Metabolic Ovarian Syndrome: From Plasticity-Dominant States to Pathological Remodeling.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Defining metabolic heterogeneity in polyendocrine metabolic ovarian syndrome based on the MTHFR C677T polymorphism: the potential pathway role of homocysteine.Journal of ovarian research · 2026Article
- Empagliflozin Targets NF-κB Signaling Through PTGS2 and TLR4 in Polycystic Ovary Syndrome: A Drug Repurposing Study and Molecular Simulation.Journal of xenobiotics · 2026Article
- Challenging prior assumptions: coexistence of polycystic ovarian morphology and endometriosis on transvaginal ultrasound.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2026Article
- Polyendocrine metabolic ovarian syndrome in pregnancy: pathophysiology and outcomes.Nature reviews. Endocrinology · 2026Review
- Distinct metabolomic profiles in lean and non-lean polyendocrine metabolic ovarian syndrome.Journal of assisted reproduction and genetics · 2026Article
- Gut microbiota in PCOS: key microbial changes, potential mechanisms and clinical applications.Journal of translational medicine · 2026Review
- Distinct pregnancy challenges in PCOS women undergoing IVF/ICSI with singleton and twin births: a propensity-matched analysis.Journal of ovarian research · 2026Article
- Opportunities and Challenges for Precision Nutrition in Gestational Obesity Management.Current obesity reports · 2026Review
- Natural Products in the Metabolic and Endocrine Modulation of Polycystic Ovary Syndrome: Current Perspectives.Nutrients · 2026Review
- ApoB and LDL partially explain the association between family history of diabetes and lower clinical pregnancy in women who conceived with PCOS.Frontiers in nutrition · 2026Article
- Genistein in polycystic ovary syndrome: mechanisms, preclinical evidence, and translational potential.Frontiers in global women's health · 2026Review
- Balancing metabolic optimization and reproductive safety in Polycystic Ovary Syndrome: a Bayesian-informed framework for GLP-1 receptor agonists.Frontiers in nutrition · 2026Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
30 authors.
Xueying Gao *State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.ORCID http://orcid.org/0000-0002-5868-5378
Shigang Zhao *State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.ORCID http://orcid.org/0000-0002-7407-9220
Yanzhi Du *Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Ziyi Yang *State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.ORCID http://orcid.org/0000-0002-4138-5598
Ye Tian *Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.
Junli Zhao *Department of Reproductive Medicine, General Hospital of Ningxia Medical University, Ningxia, China.
Xi YuanDepartment of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Singapore, Singapore.
Betania R SantosGynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Daimin WeiState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Linlin CuiState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.ORCID http://orcid.org/0000-0001-7659-9169
Junhao YanState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Yingying QinState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.ORCID http://orcid.org/0000-0002-0319-7799
Yuhua ShiState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Rong TangState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Yun SunShanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Jingmei HuState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Lingling DingState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Xueru SongDepartment of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.
Lingxia HaDepartment of Reproductive Medicine, General Hospital of Ningxia Medical University, Ningxia, China.
Jingyu LiState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
China Women’s Reproductive Metabolic Network
Heping ZhangDepartment of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-0688-4076
Poli Mara SpritzerGynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. spritzer@ufrgs.br.ORCID http://orcid.org/0000-0002-6734-7688
Bulent O YildizDivision of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey. elisabet.stener-victorin@ki.se.ORCID http://orcid.org/0000-0003-1797-7662
Elisabet Stener-VictorinDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. yildizbo@yahoo.com.ORCID http://orcid.org/0000-0002-3424-1502
Eu-Leong YongDepartment of Obstetrics and Gynaecology, National University Hospital, National University of Singapore, Singapore, Singapore. obgyel@nus.edu.sg.ORCID http://orcid.org/0000-0001-6511-770X
Xiang-Hong OuGuangdong-Hong Kong Metabolism and Reproduction Joint Laboratory, Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China. ouxianghong@163.com.
Richard S LegroDepartment of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA, USA. rsl1@psu.edu.
Han ZhaoState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China. hanzh80@sdu.edu.cn.ORCID http://orcid.org/0000-0001-9515-7534
Zi-Jiang ChenState Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China. chenzijiang@hotmail.com.ORCID http://orcid.org/0000-0001-6637-6631
Funding
Penn State Clinical and Translational Science InstituteUL1TR002014 · NCATS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI KRASCHNEWSKI, JENNIFER L. · 2016 to 2025
$33.7MAMH signaling pathway variation in PCOSR01HD100630 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI URBANEK, MARGRIT · 2020 to 2024
$3.0MThe COMET-PCOS trial - Comparing the effects of Oral Contraceptive Pills versus Metformin in the medical management of overweight/obese women with Polycystic Ovary SyndromeR01HD091350 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI DOKRAS, ANUJA · 2017 to 2021
$2.8MInositol Supplementation to Treat Reproductive and Metabolic Dysfunction in Polycystic Ovary Syndrome: A Double Blind RCT (INSUPP-PCOS)R01AT009484 · NCCIH · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LEGRO, RICHARD S. · 2018 to 2024
$2.5MEarly Intervention to Promote Cardiovascular Health of Mothers and Children in Northern AppalachiaUG3HL162971 · NHLBI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LEGRO, RICHARD S., PAUL, IAN M · 2022 to 2023
$1.4MNational Natural Science Foundation of China (National Science Foundation of China) 32370916National Natural Science Foundation of China (National Science Foundation of China) 32588201National Natural Science Foundation of China (National Science Foundation of China) 82101707NCATS NIH HHS UL1 TR002014NCCIH NIH HHS R01 AT009484NHLBI NIH HHS UG3 HL162971NICHD NIH HHS R01 HD091350NICHD NIH HHS R01 HD100630U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R01HD100630U.S. Department of Health & Human Services | National Institutes of Health (NIH) 1R43HD11427-01U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AT009484-A1U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01 HD091350-04U.S. Department of Health & Human Services | National Institutes of Health (NIH) UG3/UH3 HL162971
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.
Indexed as
Polycystic Ovary SyndromeAdultAnti-Mullerian HormoneFemaleFertilization in VitroHumansHyperandrogenismLuteinizing HormoneObesityPregnancyProspective StudiesSex Hormone-Binding GlobulinAnti-Mullerian HormoneLuteinizing HormoneSex Hormone-Binding Globulin
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