Diagnostic use of CA 125 values measured on the 2nd and 14th days of menstrual cycle in endometriosis

OBJECTIVE: Endometriosis is an inflammatory disease, that affects 10% of women in reproductive period and may cause chronic pelvic pain and infertility. The duration between first symptoms and diagnosis may be as long as 8 years. Therefore, non-invasive methods are needed for early diagnosis. Regarding many serum markers, including CA 125 and CRP, were previously studied for the early diagnosis of endometriosis. However, no serum marker could reach an ideal diagnostic performance for endometriosis. It is a known fact that, CA 125 and CRP levels increase during menstruation. We aimed to find out if this increase is more noteworthy among patients with endometriosis, and to evaluate the diagnostic performance of this if there is a noteworthy increase. METHOD: 66 patients were included in this prospective case-control study. 36 cases formed the study group (endometriosis) and the remaining 30 cases formed the control group. The patients in the study group were women, who were pre-diagnosed with endometriosis and tested for serum CA 125 and CRP on the 2nd and 14th days of menstrual cycle preoperatively (during menstruation and non-menstrual phase) and operated. The women in the control group were patients, who visited the outpatient clinic for a regular check-up without any gynecological complaints. The patients in the control group were not diagnosed with any gynecological pathologies. RESULTS: The CA 125 levels were significantly higher on the 2nd day of menstrual cycle than the 14th day in the study group (n=36) (108.15±90.33 U/mL and 58.60±39.53 U/mL, respectively, p<0.001). In the control group (n=30), the CA 125 levels were significantly higher on the 2nd day than the 14th day (22.97±15.42 U/mL and 13.82±6.82 U/mL, respectively, p<0.001). When the comparison was made between the CRP levels on the 2nd and 14th day for the study group (4.52±4.45 mg/L and 2.82±3.79 mg/L, respectively), the levels were significantly higher on the 2nd day (p<0.001). The CRP levels on the 2nd and 14th day were compared for the control group (3.44±5.17 mg/L and 2.02±2.27 mg/L, respectively) and the difference was not statistically significant (p=0.054). The CA 125 levels on the 2nd and 14th days were both higher in the study group than they were in the control group and the differences were statistically significant (p<0.001 and p<0.001, respectively). Nevertheless, the differences between the study group and the control group were not statistically significant, when the same comparison was made for the CRP levels on the 2nd and 14th days (p=0.064 and p=0.571, respectively). The difference of CA 125 and CRP levels between the 2nd and 14th days of the menstrual cycle (for the study group: ΔCA125=49.55±56.89 U/mL, ΔCRP=1.69±3.45 mg/L and for the control group ΔCA125=9.14±11.95 U/mL, ΔCRP=1.42±4.74 mg/L) were higher for both markers in the study group and the differences with the control group were statistically significant (p<0.001 for ΔCA125 and p=0,033 for ΔCRP). The CA 125 values on the 2nd and 14th days stood out as parameters with the best diagnostic performance (AUC: 0.93 for both). Regarding diagnostic performance, ΔCA125 followed (AUC:0.85). CRP levels showed insufficient diagnostic performance. When the cut-off was set as 35 U/mL for the CA 125 level tested on the 2nd day of cycle, concerning this sample, the sensitivity and specificity of the test for endometriosis were 91.6% and 83.3%, respectively. When the same cut-off value (35 U/mL) was set for the CA 125 level tested on the 14th day, the sensitivity was 72.2% and the specificity was 100% for endometriosis. The ideal cut-off level on the area under curve (AUC) for ΔCA125 was 14.85 U/mL. This cut-off value had a sensitivity of 80.6% and a specificity of 80% for endometriosis. DISCUSSION: Our data presented that the test of CA 125 on the 2nd day was the best parameter regarding sensitivity (91.6%) and the test on the 14th day had the best specificity (100%). Provided the cut-off value is set at 14.85 U/mL for the difference of CA 125 between the 2nd and 14th days, the calculated sensitivity (80.6%) and specificity (80%) were both not better than a single measurement. It may be possible to prevent the usage of unnecessary diagnostic methods, with the evaluation of CA 125 levels during different phases of menstruation (menstrual and non-menstrual phases) separately. KEYWORDS: endometriosis, CA 125, CRP, menstrual cycle