HE4

Has your gynaecologist found an ovarian cyst or mass on ultrasound and wants to assess it better? HE4 is a blood tumour marker that, together with CA 125, helps assess whether a mass is more likely benign or malignant. It does not establish a diagnosis alone and is not a cancer-detection test for women without symptoms.

Who is this test for

• women with an ovarian or pelvic cyst or mass found on ultrasound or other imaging;
• when a gynaecologist wants to calculate the ROMA index alongside CA 125, also accounting for menopause;
• women with endometriosis or fibroids and elevated CA 125, because HE4 rises less often in these benign conditions;
• women treated for ovarian cancer when an oncologist wants to monitor CA 125 together with HE4.

HE4 is not intended for screening healthy women, pregnant women or girls under 18. If bloating, abdominal or pelvic pain, or feeling full early persists for several weeks, contact a gynaecologist. Read more in the article Early signs of ovarian cancer.

What the test reveals

HE4 (human epididymal protein 4) is a protein produced in larger amounts by cells of some malignant tumours, particularly the most common type of ovarian cancer. Unlike CA 125, which also rises in many benign conditions such as endometriosis, fibroids or menstruation, HE4 is more often normal in benign gynaecological conditions.

HE4 is therefore most often used together with CA 125. When both are measured from the same sample, the ROMA index formula classifies the mass as low or high risk for malignancy. The combination is more reliable than either marker alone, but only tissue analysis after surgery provides a definitive answer. Read how tumour markers are generally used in the article Tumour markers.

The test and preparation

Blood is taken from a vein in the arm, taking a few minutes. Fasting is not required. If HE4 is tested together with CA 125, it is better to take blood after menstruation ends unless the gynaecologist advises otherwise.

• At blood collection, state whether you have kidney disease and smoke, because these may affect the result. Also mention biotin use (e.g. hair and nail supplements).
• Menopause information matters for the ROMA index, so state when your last period occurred and whether your ovaries or uterus have been removed.

What your results mean

Reference values depend on age, menopause and method and are printed on the report. The result is interpreted alongside examination, ultrasound, CA 125 and your symptoms.

• Normal HE4 means a malignant mass is less likely but does not exclude it. The gynaecologist decides on follow-up or surgery according to the overall findings.
• High HE4 means a malignant mass is more likely, not that cancer is confirmed. HE4 is also higher with impaired kidney function, in smokers and with older age, and may rise in other malignancies such as cancer of the uterine lining.
• When monitoring treated cancer the trend across several results matters more than a single value. The oncologist interprets a rise alongside examination and imaging.

How to arrange testing

You can come for blood collection without an appointment or referral at one of our branches throughout Croatia (listed on the Contactpage). Prices for all tests and panels are listed in the price list. If your gynaecologist requests HE4 together with CA 125, the ROMA indexis more cost-effective, including both markers and a risk calculation from the same sample.

Frequently asked questions

Can HE4 detect ovarian cancer?

Not as a stand-alone test. HE4 helps assess an already identified mass, usually alongside CA 125 and the ROMA index. It is not used for early cancer detection in women without a mass or symptoms.

What is the difference between HE4 and CA 125?

Both markers rise in ovarian cancer, but CA 125 also rises in many benign conditions such as endometriosis or fibroids. HE4 is more often normal in these, so together they provide a more reliable assessment.

Why is my HE4 high if I do not have cancer?

The most common reasons are impaired kidney function, smoking and older age. A doctor therefore always considers it alongside creatinine, ultrasound and other tests, not as stand-alone evidence of disease.

Should HE4 be tested preventively?

No. In women without a pelvic mass, the result has no clear meaning and may cause unnecessary worry. Regular gynaecological examinations and contacting a doctor when symptoms persist are important for prevention.