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HE4 (epididymis protein 4)
A protein used with CA-125 in the ROMA algorithm to estimate the risk of ovarian cancer in women with a pelvic mass.
Other names: HE4, WFDC2Section: Tumor markers
Updated: August 31, 2026·MedProtect editorial team Reference information — not a diagnosis or a prescription
In shortHE4 is a protein that rises in many ovarian cancers. Commonly used cutoffs are up to 70 pmol/L (up to 1750 pg/mL) before menopause and up to 140 pmol/L (3500 pg/mL) after. Combined with CA-125 in the ROMA score, it helps triage pelvic masses. It is not a standalone screening test.
Reference ranges
Group
Reference range
Premenopausal women — typical range (international reference, not a national standard)
< 70 pmol/L (< 1750 pg/mL)
Postmenopausal women — typical range (international reference, not a national standard)
< 140 pmol/L (< 3500 pg/mL)
Cutoffs most often used in the literature, summarized in an open-access review (international reference, not a national standard). Exact limits depend on the assay — the report's interval applies. Reference ranges vary between laboratories and assays — use the range printed on your own lab report.
Check your value
Enter the number from your lab report — see how it compares with the typical range. Mind the units shown in the chosen row.
A rough comparison with a typical range, not a diagnosis. Reference ranges vary between laboratories — check the range on your own report and let a clinician interpret the result.
What this marker is
HE4 is overexpressed in epithelial ovarian cancer and is less often elevated by benign conditions than CA-125. That makes the pair HE4 + CA-125 more informative than either alone when a pelvic mass is found.
Levels rise with age and with reduced kidney function, and are somewhat higher in smokers — these factors are considered when a result is borderline.
When it is high
Ovarian cancerHE4 rises in most epithelial ovarian cancers, often before symptoms; the ROMA score estimates risk.
Kidney diseaseReduced renal clearance raises the level without cancer.
Benign gynecologic conditionsEndometriosis and other conditions can cause moderate elevations.
When it is low
Expected findingMost healthy women have low values; a low HE4 does not exclude early cancer.
What can skew the result
These factors can shift the value without any disease — worth considering before a retest:
Age and menopausal statusSmokingKidney functionEndometriosis
How to prepare
Blood from a vein; no special preparation.
When a retest makes sense
An elevated result is followed up by a gynecologist, usually with CA-125 and ultrasound; trends are compared within one laboratory.
Who usually reviews this result
A result outside the reference range is usually reviewed by: a gynecologist; a gynecologic oncologist for suspicious findings. Bring your lab report and any previous results to the appointment.
Names used on lab reports
Your report may use any of these names: HE4Human epididymis protein 4WFDC2
A validated algorithm combining HE4, CA-125, and menopausal status to estimate the risk that a pelvic mass is malignant.
Is HE4 better than CA-125?
They answer slightly different questions: HE4 is raised less by benign conditions, CA-125 catches some cancers HE4 misses. Together they outperform either alone.
Can HE4 screen for ovarian cancer?
No — no blood test is currently validated for population screening of ovarian cancer.
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