The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data
Abstract Background Polycystic ovary syndrome (PCOS) is a multifaceted condition with diagnostic challenges and clinical heterogeneity across populations. Research priorities include enhanced accuracy in defining cut-offs for diagnostic features. Here, we aim to describe participant clinical feature...
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2025-07-01
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| author | Asmamaw Demis Bizuneh Sylvia Kiconco Arul Earnest Mahnaz Bahri Khomami Raja Ram Dhungana Ricardo Azziz Larisa V. Suturina Xiaomiao Zhao Alessandra Gambineri Fahimeh Ramezani Tehrani Bulent O. Yildiz Jin Ju Kim Liangzhi Xu Christian Chigozie Makwe Helena J. Teede Anju E. Joham Chau Thien Tay |
| author_facet | Asmamaw Demis Bizuneh Sylvia Kiconco Arul Earnest Mahnaz Bahri Khomami Raja Ram Dhungana Ricardo Azziz Larisa V. Suturina Xiaomiao Zhao Alessandra Gambineri Fahimeh Ramezani Tehrani Bulent O. Yildiz Jin Ju Kim Liangzhi Xu Christian Chigozie Makwe Helena J. Teede Anju E. Joham Chau Thien Tay |
| author_sort | Asmamaw Demis Bizuneh |
| collection | DOAJ |
| description | Abstract Background Polycystic ovary syndrome (PCOS) is a multifaceted condition with diagnostic challenges and clinical heterogeneity across populations. Research priorities include enhanced accuracy in defining cut-offs for diagnostic features. Here, we aim to describe participant clinical features and data harmonization in the international PCOS Phenotype in Unselected Populations (P-PUP) study. Methods We searched EMBASE and Medline (Ovid) from 1990 to October 2, 2020, in population-based, medically unbiased study cohorts. Included studies had ≥ 300 participants, directly assessed PCOS-related features, and provided Individual Participant Data (IPD). Risk of bias was assessed using the AXIS tool. Data integrity was ensured via cross-referencing, identifying outliers/implausible data, and variable harmonization. Reporting follows PRISMA-IPD guidelines, summarizing findings with frequencies and proportions. Results The study included 9979 reproductive-age women from 12 studies across eight countries (China, Iran, Italy, Nigeria, Russia, South Korea, Turkey, and the USA), representing 11 ethnicities. Ovulatory dysfunction was variably recorded, from mean menstrual cycle length, minimum or maximum cycle length, number of cycles per year, or urinary progesterone measurements. Clinical hyperandrogenism was assessed via modified Ferriman–Gallwey (mFG) scores, with a few also including acne and alopecia. Biochemical hyperandrogenism thresholds varied (95th, 97.5th, or 98th percentile of healthy controls). Polycystic ovary morphology was assessed via transvaginal, transabdominal, or transrectal approaches. Harmonization adhered to International PCOS Guidelines for ovulatory dysfunction, ethnicity-specific cut-offs for hirsutism (via k-means clustering), and 95th percentile thresholds for biochemical hyperandrogenism. PCOS prevalence ranged from 3.3 to 19.8% in the original studies and was 11.0% overall after harmonization. Conclusions The P-PUP study offers an unprecedented, ethnically diverse, medically unbiased population-based cohort, an extraordinarily valuable tool to enhance knowledge and research in PCOS. However, variability in data collection methods and definitions of PCOS diagnostic features across studies limited the ability to fully integrate data for analysis. Despite these limitations, we optimized harmonization in this IPD, and the findings provided valuable insights into the challenges of data harmonization and established a foundation for future collaborative research. Future research should focus on standardizing data collection, establishing normative cut-offs based on true natural groupings, and linking diagnostic clusters to outcomes in diverse populations. Protocol registration CRD42021267847. |
| format | Article |
| id | doaj-art-3fdd5ec73ef9494a82e9014cc4d6c6f6 |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj-art-3fdd5ec73ef9494a82e9014cc4d6c6f62025-08-20T03:43:22ZengBMCBMC Medicine1741-70152025-07-0123111910.1186/s12916-025-04221-9The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant dataAsmamaw Demis Bizuneh0Sylvia Kiconco1Arul Earnest2Mahnaz Bahri Khomami3Raja Ram Dhungana4Ricardo Azziz5Larisa V. Suturina6Xiaomiao Zhao7Alessandra Gambineri8Fahimeh Ramezani Tehrani9Bulent O. Yildiz10Jin Ju Kim11Liangzhi Xu12Christian Chigozie Makwe13Helena J. Teede14Anju E. Joham15Chau Thien Tay16Monash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMonash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversitySchool of Public Health and Preventive Medicine, Monash UniversityMonash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMonash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversityDepartments of Obstetrics and Gynecology, and Medicine, University of Alabama at BirminghamDepartment of Reproductive Health Protection, Scientific Center for Family Health and Human Reproduction ProblemsDepartment of Reproductive Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical UniversityDepartment of Medical and Surgical Science-DIMEC, Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria Di BolognaReproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical SciencesDivision of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University School of MedicineDivision of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Healthcare System Gangnam Center, Seoul National University HospitalDepartment of Obstetrics and Gynecology, West China Second University Hospital, Sichuan UniversityDepartment of Obstetrics and Gynaecology, College of Medicine, University of Lagos, Idi-Araba, Lagos, NigeriaMonash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMonash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMonash Centre for Health Research and Implementation, Faculty of Medicine, Nursing and Health Sciences, Monash UniversityAbstract Background Polycystic ovary syndrome (PCOS) is a multifaceted condition with diagnostic challenges and clinical heterogeneity across populations. Research priorities include enhanced accuracy in defining cut-offs for diagnostic features. Here, we aim to describe participant clinical features and data harmonization in the international PCOS Phenotype in Unselected Populations (P-PUP) study. Methods We searched EMBASE and Medline (Ovid) from 1990 to October 2, 2020, in population-based, medically unbiased study cohorts. Included studies had ≥ 300 participants, directly assessed PCOS-related features, and provided Individual Participant Data (IPD). Risk of bias was assessed using the AXIS tool. Data integrity was ensured via cross-referencing, identifying outliers/implausible data, and variable harmonization. Reporting follows PRISMA-IPD guidelines, summarizing findings with frequencies and proportions. Results The study included 9979 reproductive-age women from 12 studies across eight countries (China, Iran, Italy, Nigeria, Russia, South Korea, Turkey, and the USA), representing 11 ethnicities. Ovulatory dysfunction was variably recorded, from mean menstrual cycle length, minimum or maximum cycle length, number of cycles per year, or urinary progesterone measurements. Clinical hyperandrogenism was assessed via modified Ferriman–Gallwey (mFG) scores, with a few also including acne and alopecia. Biochemical hyperandrogenism thresholds varied (95th, 97.5th, or 98th percentile of healthy controls). Polycystic ovary morphology was assessed via transvaginal, transabdominal, or transrectal approaches. Harmonization adhered to International PCOS Guidelines for ovulatory dysfunction, ethnicity-specific cut-offs for hirsutism (via k-means clustering), and 95th percentile thresholds for biochemical hyperandrogenism. PCOS prevalence ranged from 3.3 to 19.8% in the original studies and was 11.0% overall after harmonization. Conclusions The P-PUP study offers an unprecedented, ethnically diverse, medically unbiased population-based cohort, an extraordinarily valuable tool to enhance knowledge and research in PCOS. However, variability in data collection methods and definitions of PCOS diagnostic features across studies limited the ability to fully integrate data for analysis. Despite these limitations, we optimized harmonization in this IPD, and the findings provided valuable insights into the challenges of data harmonization and established a foundation for future collaborative research. Future research should focus on standardizing data collection, establishing normative cut-offs based on true natural groupings, and linking diagnostic clusters to outcomes in diverse populations. Protocol registration CRD42021267847.https://doi.org/10.1186/s12916-025-04221-9Data harmonizationAndrogensPolycystic ovary syndromePCOSHirsutismAcne |
| spellingShingle | Asmamaw Demis Bizuneh Sylvia Kiconco Arul Earnest Mahnaz Bahri Khomami Raja Ram Dhungana Ricardo Azziz Larisa V. Suturina Xiaomiao Zhao Alessandra Gambineri Fahimeh Ramezani Tehrani Bulent O. Yildiz Jin Ju Kim Liangzhi Xu Christian Chigozie Makwe Helena J. Teede Anju E. Joham Chau Thien Tay The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data BMC Medicine Data harmonization Androgens Polycystic ovary syndrome PCOS Hirsutism Acne |
| title | The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data |
| title_full | The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data |
| title_fullStr | The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data |
| title_full_unstemmed | The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data |
| title_short | The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data |
| title_sort | pcos phenotypes in unselected populations p pup study participant clinical features and data harmonization on analysis of individual participant data |
| topic | Data harmonization Androgens Polycystic ovary syndrome PCOS Hirsutism Acne |
| url | https://doi.org/10.1186/s12916-025-04221-9 |
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