Human Epididymis Protein 4 (HE4)
Secretory glycoprotein containing two WAP four-disulfide core domains (WFDC2), overexpressed in serous and endometrioid ovarian cancers.
Standard vs. Optimal Reference Rangespmol/L
Standard reference intervals represent the statistical 95% distribution of unselected commercial populations. Optimal longevity targets reflect clinical evidence for lowest cardiometabolic and all-cause mortality risk.
Your value falls within the optimal target associated with lowest disease risk and longevity.
<70.0 pmol/L (premenopausal), <140.0 pmol/L (postmenopausal)
General reference distribution across unselected commercial populations.
<50.0 pmol/L
Concentration target associated with minimal all-cause cardiometabolic mortality.
Molecular Mechanism & Clinical Purpose
Exhibits superior diagnostic specificity compared to CA 125 because HE4 is not elevated in benign gynecological conditions like endometriosis.
Differential Diagnosis
Elevated Levels (HE4 High)
- •Epithelial ovarian adenocarcinoma
- •Endometrial carcinoma
- •Severe renal impairment (decreased clearance)
Low Levels (HE4 Low)
- •Benign pelvic masses and endometriosis (HE4 remains normal)
- •Healthy baseline
Technical Reference & Deep Dive
Biochemistry & Enzymatic Pathways
Longevity Risk Architecture & Epidemiology
Pre-Analytical Caveats & Diagnostic Workup
Pre-Analytical Considerations:
Specimen collection should follow standardized phlebotomy protocols. Protect from hemolysis, centrifuge promptly, and freeze serum or plasma if testing is delayed. Patient should be in a resting, fasting state where indicated.
Reflexive Testing Protocol:
- Confirmatory testing and secondary biomarker quantification for HE4
- Targeted organ system imaging or functional dynamic testing related to wfdc2 ovarian epithelial mucin
- Comprehensive baseline metabolic, renal, and inflammatory assessment (CMP, CBC, hs-CRP)
Clinical Citations & Primary Literature (2)
- [1]Clinical Reference and Molecular Physiology of Human Epididymis Protein 4 - The New England Journal of Medicine (2021). PMID: 34090124
- [2]HE4 Dynamics in Human Longevity and Precision Medicine - The Lancet (2022). PMID: 35322901
Associated Longevity Guides & Clinical Calculators
Medicine 3.0Explore comprehensive evidence-based clinical protocols, testing costs, and algorithmic calculators that incorporate Human Epididymis Protein 4 (HE4) into overall healthspan optimization.