Home Medicine Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study
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Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study

  • Jiaming Wu , Penghui Feng , Jinming Zhang , Xingtong Chen , Rong Chen EMAIL logo , Min Luo EMAIL logo and Falin He EMAIL logo
Published/Copyright: May 30, 2025

Abstract

Objectives

Significant changes in clinical biochemical markers occur during the peri-menopausal period. Traditional population-based reference intervals (popRIs) may not reflect individual physiological variability, limiting clinical interpretation. This study aimed to establish personalized reference intervals (prRIs) for menopausal women and compare them with popRIs.

Methods

We analyzed 899 healthy women aged 35–64 from the Peking Union Medical College Hospital Aging Longitudinal Cohort of Women in Midlife (PALM) cohort. 13 biochemical markers were evaluated across reproductive, menopausal transition, and postmenopausal stages. Six key biomarkers were selected through Kruskal–Wallis tests and ranked by their importance in menopausal status classification using a Random Forest model. Biological variation (BV) data were used to calculate total variation (TV) and index of individuality (II). The prRIs were constructed based on BV estimates, and the reference interval index (RII) was applied to compare popRIs and prRIs.

Results

ALT, TG, and FSH showed significant differences across menopausal stages and ranked highly in the Random Forest model. These markers also had large BV and differed across three menopausal stages. Most II values ranged from 0.6 to 1.4, and all median RII values were below 1.0, suggesting limited utility of popRIs. Crea in reproductive women had the highest proportion of RII>1.0, while FSH showed RII<0.5 in over 90 % of women in the menopausal transition.

Conclusions

For women in the menopausal transition with high BV estimates, combining popRIs with prRIs improves interpretation. Larger, more diverse cohorts are needed to validate and optimize prRIs for clinical application.


Corresponding authors: Falin He, National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, 100730, China; and Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China, E-mail: ; and Min Luo and Rong Chen, Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China, E-mail: (M. Luo), (R. Chen)
Jiaming Wu, Penghui Feng and Jinming Zhang contributed equally to this work.

Award Identifier / Grant number: 2023M740320

Funding source: Special Support Plan for Clinical Research in Central High-level Hospital of PUMCH

Award Identifier / Grant number: Grant 2022-PUMCH-A-116

Acknowledgments

We are grateful to all the staff members for taking part in this study. We thank the participants for their cooperation and sample contributions.

  1. Research ethics: This study was approved by the Ethics Committee of Peking Union Medical College Hospital.

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: Large language models (e.g. ChatGPT) were used to assist in language polishing. All scientific content was created and validated by the authors.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This work was supported by Special Support Plan for Clinical Research in Central High-level Hospital of PUMCH (Grant 2022-PUMCH-A-116), and China Postdoctoral Science Foundation (2023M740320).

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0658).


Received: 2025-05-30
Accepted: 2025-08-04
Published Online: 2025-05-30
Published in Print: 2025-11-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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