Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study.
Level 3 - non-randomized controlled study
Cross-sectional cohort analysis of biomarker variation across menopausal stages
PubMed 40802590 · doi:10.1515/cclm-2025-0658
What was done
Analyzed 13 biochemical markers across reproductive, menopausal transition, and postmenopausal stages in 899 healthy women aged 35–64 from the Peking Union Medical College Hospital Aging Longitudinal Cohort of Women in Midlife (PALM). Six key biomarkers selected via Kruskal-Wallis testing were ranked using a Random Forest model. Researchers calculated biological variation (BV), total variation (TV), and index of individuality (II), then constructed personalized reference intervals (prRIs) and compared them to population-based reference intervals (popRIs) using the reference interval index (RII).
What was found
ALT, TG, and FSH differed significantly across menopausal stages, ranked highest in the Random Forest model, and exhibited large BV that varied across stages. Most markers had II values between 0.6 and 1.4, and all median RII values were below 1.0. Creatinine in reproductive women had the highest proportion of RII > 1.0, while FSH showed RII < 0.5 in over 90% of women during the menopausal transition.
Why it matters
Standard population reference intervals often fail to capture individual physiological variation during menopausal transitions. Implementing personalized reference intervals for high-variation markers may improve clinical assessment and monitoring during peri-menopause.
Limits
The study is restricted to a single-center cohort in China, limiting generalizability across diverse ethnic and geographical populations. The abstract does not report specific baseline numerical estimates for biological variation or long-term clinical outcome validations.
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