Redefining "Normal" for hCG in postmenopausal women: 97.5th percentile reference intervals and 99th percentile thresholds across four chemiluminescence immunoassay systems.

BACKGROUND AND OBJECTIVE: Physiological human chorionic gonadotropin (hCG) elevations in postmenopausal women are prone to misclassification as pathological. Substantial inter-system variation exists among immunoassays, and system-specific reference intervals (RIs) for this population have not been established. This study aimed to establish 97.5th percentile RIs and 99th percentile thresholds for serum hCG in healthy postmenopausal women across four chemiluminescence immunoassay (CLIA) systems. METHODS: A total of 460 postmenopausal women were enrolled. Serum hCG was measured using four immunoassay systems: Beckman UniCel DxI 800 (A), Siemens Atellica IM 1600 (B), Roche Cobas e 801 (C), and Abbott ARCHITECT i2000SR (D). Analytical precision was evaluated according to Clinical and Laboratory Standards Institute (CLSI) EP15-A2. Samples with hCG > 5.0 IU/L (> 6.0 IU/L for System B) underwent polyethylene glycol (PEG) precipitation to exclude macro-complex interference. Spearman rank correlation was used to assess correlations between hCG and age, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). One-sided upper reference limits (97.5th and 99th percentiles) were estimated using the non-parametric method. RESULTS: 355 subjects were included in the final analysis. The imprecision of all four systems met the analytical performance criterion. Serum hCG showed poor positive correlations with age (Spearman r = 0.146-0.198, all P < 0.01). Fair correlations were observed between hCG and FSH (r = 0.341, 95% CI: 0.246-0.430) and between hCG and LH (r = 0.428, 95% CI: 0.339-0.509). The 97.5th percentile RIs were < 7.1, < 8.2, < 5.7, and < 5.9 IU/L for Systems A-D, respectively; the 99th percentile thresholds were < 8.8, < 9.3, < 7.1, and < 7.8 IU/L. System B consistently yielded the highest thresholds, while System C produced the lowest. CONCLUSION: The established 97.5th percentile RIs and 99th percentile thresholds provide reliable, system-specific quantitative criteria for differentiating pituitary-derived from pathological hCG elevations.