Redefining "Normal" for hCG in postmenopausal women: 97.5th percentile reference intervals and 99th percentile thresholds across four chemiluminescence immunoassay systems.
The study establishes important reference intervals for hCG in postmenopausal women, which can aid in differentiating normal from pathological elevations.
Where it sits
this study against the rest of the hcg (human chorionic gonadotropin) corpusSummary and findings
This study measured serum hCG levels in 460 postmenopausal women across four immunoassay systems to establish reference intervals and thresholds. The 97.5th percentile reference intervals were found to be <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.
Abstract
<h4>Background and objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>The established 97.5th percentile RIs and 99th percentile thresholds provide reliable, system-specific quantitative criteria for differentiating pituitary-derived from pathological hCG elevations.
Background
This paper addresses the need for accurate reference intervals for serum hCG in postmenopausal women, as physiological elevations are often misclassified as pathological. Prior studies have indicated substantial inter-system variation among immunoassays, but specific reference intervals for this demographic have not been established. This study is significant as it aims to provide reliable, system-specific criteria to differentiate between normal and pathological hCG levels.
Methods
The study enrolled 460 postmenopausal women, measuring serum hCG using four different immunoassay systems: Beckman UniCel DxI 800, Siemens Atellica IM 1600, Roche Cobas e 801, and Abbott ARCHITECT i2000SR. Analytical precision was assessed according to CLSI EP15-A2 guidelines. Samples with hCG levels above specified thresholds underwent further analysis to exclude interference. The study used Spearman rank correlation to evaluate relationships between hCG and age, FSH, and LH.
Results
The primary endpoint revealed that the 97.5th percentile reference intervals for serum hCG 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. Correlations between hCG and FSH and LH were fair, with r values of 0.341 and 0.428, respectively, both with 95% confidence intervals reported. Poor correlations with age were also noted, with Spearman r values ranging from 0.146 to 0.198.
Interpretation
The established reference intervals and thresholds provide a clearer framework for interpreting hCG levels in postmenopausal women, which is crucial given the potential for misclassification. While the correlations with FSH and LH are statistically significant, the clinical significance of these findings may be limited by the relatively low effect sizes. Additionally, the study's reliance on specific immunoassay systems may restrict the applicability of these results to other settings or populations.
Key findings
- 355 subjects included in final analysis.
- 97.5th percentile RIs were < 7.1, < 8.2, < 5.7, and < 5.9 IU/L for Systems A-D, respectively.
- 99th percentile thresholds were < 8.8, < 9.3, < 7.1, and < 7.8 IU/L.
- Spearman correlation between hCG and FSH was r = 0.341, 95% CI: 0.246-0.430.
- Spearman correlation between hCG and LH was r = 0.428, 95% CI: 0.339-0.509.
- Poor positive correlations with age (Spearman r = 0.146-0.198, all P < 0.01).
Limitations
- small n=460 for specific assay systems
- study may not be generalizable beyond tested population
- reliance on specific immunoassay systems limits broader applicability
- no long-term follow-up reported