Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age.

OBJECTIVE The purpose of this study was to establish normal ranges for human epididymis protein 4 (HE4) serum levels in healthy women. STUDY DESIGN HE4 levels were measured in healthy women and analyzed by age, menopausal status, and pregnancy status. Upper 95th percentiles were determined for normal ranges. RESULTS Serum samples from 1101 healthy women and 67 pregnant women were analyzed. Above the age of 40 years significant elevations in HE4 concentrations emerged with advancing age. The upper 95th percentile for HE4 levels was 89 pmol/L for premenopausal women, 128 pmol/L for postmenopausal women, and 115 pmol/L for all women. There was a significant difference in the median serum HE4 levels in premenopausal women (46.6 pmol/L) compared with postmenopausal women (57.6 pmol/L; P < .001). In pregnant women, median HE4 concentrations were significantly lower than their premenopausal counterparts (P < .001). CONCLUSION HE4 serum concentrations vary significantly on the basis of age. These variations must be considered when the upper limit of normal for HE4 is determined.