Ovarian tumor marker HE4 is differently expressed during the phases of the menstrual cycle in healthy young women

Abstract

The objective of the present study was to investigate in healthy young women the fluctuations in serum concentration of human epididymal secretory protein human epididymis-specific protein 4 (HE4) and CA125 during the phases of the menstrual cycle and the correlation between HE4 and CA125 values and age. Forty women with regular menstrual cycles were included in the study. Pelvic and transvaginal ultrasound were performed in order to exclude ovarian pathologies. Blood samples were collected at follicular (FP), ovulatory (OP), and luteal (LP) phases of the hormonal cycle. The values of HE4 (expressed as picomoles per liter) observed were (mean ± SEM) 39.1 ± 1.1 (FP), 45.3 ± 1.19 (OP), and 42.0 ± 1.3 (LP). The difference between FP and OP was statistically significant (p = 0.0002). By contrast, serum CA125 levels (expressed as units per milliliter) were 14.35 ± 0.66 (FP), 13.15 ± 0.54 (OP), and 13.70 ± 0.54 (LP), respectively. The levels of HE4 observed in serum samples of women below 35 years were 37.5 ± 1.28 in the FP, 46.6 ± 1.4 in the OP, and 42.8 ± 1.49 in the LP. In this group, a statistically significant difference was observed in the FP compared with the OP (p < 0.0001), whereas no statistically significant difference was observed during the different hormonal phases in the group of women over 35. In conclusion, the correct interpretation of laboratory data is essential to define a threshold of normality, and for what concerns HE4 levels, the menstrual cycle phase-dependent variability appears indicated in the interpretation of the results.

The role of HE4 and CA125 in differentiation between malignant and non-malignant endometrial pathologies

“…This statistically significant difference was not observed in patients > 35 years. Serum CA125 level was not significantly different considering different phases of the menstrual cycle in both age groups [20].…”

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

“…Anastasi et al enrolled 50 women with regular menstrual cycles, aged 20-49 years, and measured their serum HE4 levels at postmenstrual days 7, 14, and 21 [44]. They found that serum HE4 levels fluctuated during the phase of menstrual cycle, and the highest levels were detected in the ovulatory phase (45.3 ± 1.19 pM) in comparison to the follicular (39.1 ± 1.1 pM) and luteal phases (42.0 ± 1.3 pM) in women younger than 35 years.…”

Comparison of Serum Human Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in Patients with Malignant and Nonmalignant Diseases

“…The diagnostic sensitivity of CA 125 in ovarian cancer is related to tumor stage, with abnormal CA 125 serum concentrations seen in approximately 50% of patients with stage I disease and 80%-90% of patients with stages III-IV disease (3)(4)(5)(6)(7)(8)(9). However, the most important problem with CA 125 is its low diagnostic specificity, with abnormally high concentrations found in malignancies of different origin, including nonovarian gynecologic cancers (endometrium, endocervix), other epithelial tumors (lung cancer), and nonepithelial malignancies such as lymphomas (4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). High serum CA 125 concentrations may be also found in several benign diseases, including effusions, liver or renal failure, and several benign gynecologic conditions such as ovarian cysts, myomas, and, primarily in premenopausal women, endometriosis (3,4,(7)(8)(9)16 ).…”

“…However, the most important problem with CA 125 is its low diagnostic specificity, with abnormally high concentrations found in malignancies of different origin, including nonovarian gynecologic cancers (endometrium, endocervix), other epithelial tumors (lung cancer), and nonepithelial malignancies such as lymphomas (4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). High serum CA 125 concentrations may be also found in several benign diseases, including effusions, liver or renal failure, and several benign gynecologic conditions such as ovarian cysts, myomas, and, primarily in premenopausal women, endometriosis (3,4,(7)(8)(9)16 ). Likewise, CA 125 concentrations may fluctuate throughout the menstrual cycle and pregnancy (16 -18 ).…”