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. 2025 Jul 15;23(1):420.
doi: 10.1186/s12916-025-04221-9.

The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data

Asmamaw Demis Bizuneh  1 , Sylvia Kiconco  1 , Arul Earnest  2 , Mahnaz Bahri Khomami  1 , Raja Ram Dhungana  1 , Ricardo Azziz  3 , Larisa V Suturina  4 , Xiaomiao Zhao  5 , Alessandra Gambineri  6 , Fahimeh Ramezani Tehrani  7 , Bulent O Yildiz  8 , Jin Ju Kim  9 , Liangzhi Xu  10 , Christian Chigozie Makwe  11 , Helena J Teede  1   12 , Anju E Joham #  1   12 , Chau Thien Tay #  13   14
Affiliations

The PCOS Phenotypes in Unselected Populations (P-PUP) study: participant clinical features and data harmonization on analysis of individual participant data

Asmamaw Demis Bizuneh et al. BMC Med. .

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.

Keywords: Acne; Androgens; Data harmonization; Female pattern hair loss; Hirsutism; IPD; Individual participant data; PCOS; Phenotype; Polycystic ovary; Polycystic ovary syndrome.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval for the P-PUP study was obtained from the Monash University Human Research Ethics Committee (HUMREC) (ID: 26938). Additionally, each study within the research project received ethical approval from the relevant Human Research Ethics Committee. Consent for publication: Not applicable. Competing interests: AEJ serves as a Board member for Androgen Excess and Polycystic Ovary Syndrome, received honoraria for presentations at educational events at Novo Nordisk, Boehringer and Merck, and is an employee of Monash Health. CTT serves as Chair of CRE-WHiRL ECR Group 2020-2023 and AEPCOS EC-SIG group 2020-2022, as a committee member of the Endocrine Society of Australia’s ECR Group. AG serves on the Editorial Board for the European Journal of Endocrinology and on the Advisory Board of the Italian Society of Endocrinology. RA serves as a consultant to May Health, Core Access Surgical Technologies, Spruce Biosciences, and Postera; is an investor in Martin Imaging; received honoraria for speaking from the Davidson-Mestman course, Merck and Stya Paul Oration; and serves on the Editorial Board for the Journal of Clinical Endocrinology and Metabolism, on the Board of Trustees for the Endocrine Society, as a member of the DSMB for grant NCT03625531; ChiCTR180001730 to The First Affiliated of Guangzhou Medical University and grant for the SUPER study to the University of Michigan, and previously served as CEO of the American Society for Reproductive Medicine. All the other authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
PRISMA IPD flow diagram for P-PUP study selection
Fig. 2
Fig. 2
Flow chart for study participant selection. Note: TSH, prolactin, and 17-OHP were not consistently collected across the total populations in the studies, as some studies collect the data on women suspected of having PCOS
Fig. 3
Fig. 3
Ethnicity distribution of the study participants
See this image and copyright information in PMC

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