HE4 (Human Epididymis Protein 4) Unit Converter
HE4 (Human Epididymis Protein 4) Unit Converter
HE4 is reported in pmol/L by every assay, so the only conversion on this page is to nmol/L and it is prefix arithmetic. The useful part is what the number is for: HE4 earns its place inside the ROMA index with CA 125 and menopausal status, and its advantage over CA 125 is what it does not rise in.
HE4 converter
Molar prefixes onlyHE4 70 pmol/L
The whole ladder, and the unit that is missing from it
so pmol/L ÷ 1,000 = nmol/L, and nmol/L × 1,000 = pmol/L
ng/mL: no conversion is offered
- pmol/L
- the unit every HE4 assay reports and the unit every published cut-off, reference interval and ROMA equation expects. If your report is in pmol/L, no conversion is needed at all
- nmol/L
- a thousand picomoles make a nanomole, so this is the pmol/L figure divided by a thousand. It turns a typical result of 70 into 0.070, which is why nobody reports HE4 this way — but it appears occasionally and is the only other unit this measurand has
- no ng/mL
- deliberately absent. HE4 is the WFDC2 gene product, a small glycosylated protein, and the picomolar figure is a reporting convention against an assay calibrator rather than a measured amount of substance. There is no agreed grams-per-mole to convert it with, so a mass unit here would be an invented molecular weight presented as a unit conversion
- what pmol/L is doing on a protein
- carrying the convention. Because the molar unit came first for this analyte and every calibrator, cut-off and algorithm was built in it, the molar family is the right one to offer and the mass family is the one that has no defensible entry
- the ROMA index
- takes HE4 in pmol/L, CA 125 in U/mL and menopausal status, and returns a percentage. Feed it a nanomolar HE4 and the logarithm will accept the number and give a wrong answer, silently
Worked example
HE4 70 pmol/L
70 ÷ 1,000 = 0.070 nmol/L — the same quantity, and the reason nobody uses that unit
Below the 140 pmol/L cut-off two reference laboratories publish, and just above the upper limit of 68.79 pmol/L reported for healthy premenopausal women
With a CA 125 of 45 U/mL in a postmenopausal woman, this gives a ROMA of about 30% — computed on the ROMA index calculator
There is no ng/mL equivalent to quote, and any site that offers one has assumed a molecular weight
HE4 reference figures, and whose they are
| Source | Method | Figure (pmol/L) | What it is |
|---|---|---|---|
| Mayo Clinic Laboratories (HE4) | Roche Elecsys HE4, electrochemiluminescence immunoassay | ≤ 140 | The reported reference value for females, unstratified by menopausal status |
| ARUP Laboratories | Roche HE4 electrochemiluminescent immunoassay | 0–140 | The reported reference interval, with "not a stand-alone test for ovarian cancer screening or diagnosis" |
| Reference-interval study, healthy premenopausal women | Roche ECLIA on cobas e601 | 29.30–68.79 | 2.5th to 97.5th centile in a healthy population |
| Reference-interval study, healthy postmenopausal women | Roche ECLIA on cobas e601 | 35.96–114.43 | As above; note the upper limit is 66% higher than the premenopausal one |
| A second ECLIA study, 95th-centile upper limits | Roche cobas e601 | 65.87 premenopausal, 90.76 postmenopausal | The same study found HE4 and ROMA rise with age while CA 125 falls |
| Assay measuring range | Roche ECLIA | 15.0–1,500 | Results below or above it are not numbers |
Why HE4 exists: elevation in benign disease, HE4 against CA 125
| Condition | HE4 elevated in | CA 125 elevated in |
|---|---|---|
| Benign gynaecological disease overall | 8% | 29% |
| Endometriosis | 3% | 67% |
| Uterine fibroids | 8% | 26% |
| Dermoid cysts | 1% | 21% |
| Inflammatory disease | 10% | 37% |
| Serous ovarian tumours (benign) | 8% | 20% |
What raises HE4 without ovarian cancer
| Cause | What is stated about it |
|---|---|
| Renal impairment | Mayo Clinic Laboratories lists "kidney or liver disease" among the conditions in which mild elevations occur. HE4 is a small protein and reduced glomerular filtration raises its concentration, so a raised HE4 in someone with chronic kidney disease should be read against their renal function — check the CKD-EPI 2021 eGFR calculator. No reliable per-stage figure is published here: the quantified series that came to hand was retracted in 2021 and is not quoted. |
| Increasing age | An electrochemiluminescence reference-interval study found HE4 and ROMA increase with age while CA 125 decreases. This is the main reason the postmenopausal interval is higher, and it is a property of the marker rather than of any disease. |
| Hypertension and congestive heart failure | Both are named by Mayo among the benign causes of mild elevation. |
| Liver disease | Named alongside kidney disease in the same caution. |
| Endometrial cancer, and some non-gynaecological malignancy | HE4 is raised in endometrial as well as ovarian cancer, so an elevation is not specific to an ovarian primary. |
| Pregnancy | Reference intervals derived in pregnant women differ from the non-pregnant ones, so a non-pregnant cut-off does not transfer. |
One unit, one prefix step, and a marker that only works in company
This is the shortest unit ladder on the site. HE4 is reported in picomoles per litre by every assay in clinical use, every published cut-off is in picomoles per litre, and the only other unit the measurand has is nanomoles per litre, which is the same figure divided by a thousand. A typical result of 70 pmol/L becomes 0.070 nmol/L, which is why the nanomolar form is essentially never used. If your report says pmol/L, there is nothing to convert.
What is not on the ladder is a mass unit, and that absence is deliberate rather than an omission. HE4 is the product of the WFDC2 gene, a small glycosylated secreted protein, and the picomolar figure an analyser prints is a reporting convention anchored to the manufacturer’s calibrator — not an amount of substance computed from a molecular weight. There is no agreed grams-per-mole for the circulating protein to divide a nanogram-per-millilitre figure by, so a mass-to-molar conversion for HE4 would be an assumed molecular weight wearing the clothes of a unit conversion. The molar prefixes are honest arithmetic; the mass bridge is not, so it is not offered. The same logic in reverse is why this page keeps the molar unit at all: for this analyte the molar figure is the primary one, the calibrators and the algorithms were all built in it, and the mass family is the one with no defensible entry.
The clinically important thing about an HE4 result is that it is almost never read on its own. Its established uses are two. The first is inside the Risk of Ovarian Malignancy Algorithm, which takes HE4 in pmol/L, CA 125 in U/mL and menopausal status and returns a percentage risk that a woman with an adnexal mass has an epithelial ovarian cancer, with different cut-offs before and after menopause — that is the ROMA index calculator, and it is where a single HE4 value should usually go. The second is serial monitoring of treated epithelial ovarian cancer for recurrence or progression, which is the indication both Mayo and ARUP name on their test pages, and in which the patient is her own control. Neither laboratory will support it as a screening test, and both say so in as many words.
The reason a second marker was worth adding to CA 125 at all is specificity in benign disease, and it is quantifiable. In 1,042 women sampled before surgery for a pelvic mass, CA 125 was raised in twenty-nine per cent of those with benign disease and HE4 in eight per cent. The endometriosis subgroup is the headline: CA 125 was elevated in sixty-seven per cent of them and HE4 in three. Endometriosis is common, it presents with pelvic pain and an adnexal mass, and it is the commonest single reason a CA 125 pushes a premenopausal woman towards an oncology referral she does not need. Uterine fibroids, dermoid cysts and inflammatory disease follow the same pattern with smaller margins. HE4’s contribution is not that it detects more cancer; it is that it says "no" more often when the answer is no. Read the CA 125 converter alongside this page, because the two markers’ failure modes are almost complementary.
Two cautions on the number itself. HE4 rises with declining renal function — Mayo names kidney disease among the benign causes of elevation, and the mechanism is unsurprising for a small protein cleared by the kidney — so a raised HE4 in a patient with chronic kidney disease should be interpreted against their eGFR before it is interpreted against a cut-off. No per-stage figure is published on this page, because the quantified series that presents itself first in the literature was retracted in 2021 and no substitute could be verified; the direction is well supported, the magnitude is not. And HE4 rises with age independently of disease, while CA 125 falls, which is why the postmenopausal reference interval runs about two thirds higher at its upper limit and why menopausal status is an input to the algorithm rather than a footnote to it.
Frequently asked questions
How do I convert HE4 from pmol/L to nmol/L?
Divide by 1,000. An HE4 of 70 pmol/L is 0.070 nmol/L, and 140 pmol/L is 0.140 nmol/L. It is pure prefix arithmetic with no measured constant in it, and the nanomolar form is almost never used because it turns every clinically relevant result into a string of leading zeros.
Why is HE4 not reported in ng/mL?
Because there is no agreed molecular weight for the circulating protein to convert with. HE4 is a small glycosylated protein and the picomolar result is a convention against the manufacturer’s calibrator rather than an amount of substance derived from a molar mass, so a ng/mL figure would require assuming a molecular weight and presenting that assumption as a conversion. Every published cut-off, reference interval and ROMA equation is in pmol/L, so nothing is lost.
What is a normal HE4?
Mayo Clinic Laboratories and ARUP both report 140 pmol/L or below on the Roche Elecsys assay, unstratified. In healthy populations on the same platform the 2.5th to 97.5th centiles are about 29 to 69 pmol/L before menopause and 36 to 114 after it, so the clinical cut-off deliberately sits above the healthy range for specificity. Results from different HE4 methods are not interchangeable, so use the interval on your own report.
Is HE4 useful on its own or only inside ROMA?
Almost always in company. The two indications the large reference laboratories support are the ROMA index for triaging an adnexal mass — HE4 with CA 125 and menopausal status — and serial monitoring of treated epithelial ovarian cancer, where the trend matters more than the absolute value. Neither laboratory supports HE4 as a stand-alone screening or diagnostic test, and a single value read against a cut-off answers a narrower question than most people asking it intend.
Does kidney disease raise HE4?
Yes. Mayo Clinic Laboratories names kidney disease, along with liver disease, hypertension and congestive heart failure, among the benign conditions in which mild HE4 elevations occur, and the mechanism expected for a small renally handled protein is reduced clearance. Interpret a raised HE4 against the patient’s eGFR. This page does not publish a figure for how much HE4 rises per stage of chronic kidney disease, because the quantified series most often cited for it was retracted in 2021.
Is HE4 better than CA 125?
It is more specific in benign disease, which is a different claim. In 1,042 women with a pelvic mass, HE4 was raised in 8% of benign disease against CA 125’s 29%, and in endometriosis in 3% against 67%. That is where the value lies: fewer false alarms in premenopausal women, who are exactly the group in whom CA 125 performs worst. The two are used together rather than in competition, because their weaknesses are largely complementary.
Related calculators
References
- Mayo Clinic Laboratories. Human Epididymis Protein 4, Serum (HE4, test 62137). Reference value "<or =140 pmol/L"; Roche Elecsys HE4 electrochemiluminescence immunoassay; "This test should not be used as a screening test for ovarian cancer"; mild elevations in benign gynecologic conditions, hypertension, congestive heart failure, and kidney or liver disease.
- ARUP Laboratories. Human Epididymis Protein 4 (HE4), test 2003020. Reference interval 0–140 pmol/L; Roche HE4 electrochemiluminescent immunoassay; "Results obtained with different test methods or kits cannot be used interchangeably"; "Not a stand-alone test for ovarian cancer screening or diagnosis".
- Moore RG, Miller MC, Steinhoff MM, et al. Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders. Am J Obstet Gynecol. 2012;206(4). 1,042 women sampled before surgery for a pelvic mass; HE4 elevated in 8% of benign disease against 29% for CA 125, and in endometriosis 3% against 67%.
- Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women. J Ovarian Res. 2015. doi:10.1186/s13048-015-0201-z. Roche ECLIA on cobas e601, measuring range 15.0–1500 pmol/L; healthy premenopausal 29.30–68.79 pmol/L, postmenopausal 35.96–114.43 pmol/L.
- The reference intervals for HE4, CA125 and ROMA in healthy female with electrochemiluminescence immunoassay. Clin Chim Acta. 2013. Upper limits of 65.87 pmol/L premenopausal and 90.76 pmol/L postmenopausal; HE4 and ROMA increase with age while CA 125 decreases.
- UniProt Q14508 (WFDC2_HUMAN) — WAP four-disulfide core domain protein 2, the HE4 gene product.
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.