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Updated: Oct 24, 2025

Surgical Techniques to Optimize Ovarian Reserve during Laparoscopic Cystectomy for Ovarian Endometrioma
Published on: January 22, 2022
Consideration should be given to smoking, endometriosis, renal function (eGFR) and age when interpreting CA125 and
Maria Lycke1, Benjamin Ulfenborg2, Jacob Malchau Lauesgaard1
1Department of Obstetrics and Gynecology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg and Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Objectives:
To evaluate the impact of different biologic, histopathologic and lifestyle factors on serum levels of human epididymis protein 4 (HE4) and Cancer antigen 125 (CA125) in the diagnostic work up of women with an ovarian cyst or pelvic tumor.
Methods:
The statistical evaluation was performed on a population of 445 women diagnosed with a benign ovarian disease, included in a large Swedish multicenter trial (ClinicalTrials.gov NCT03193671). Multivariable logistic regression analyses were performed to distinguish between the true negatives and false positives through adjusting for biologic, histopathologic and lifestyle factors on serum samples of CA125 and HE4 separately. The likelihood ratio test was used to determine statistical significance and Benjamini-Hochberg correction to adjust for multiple testing.
Results:
A total of 31% of the women had false positive CA125 but only 9% had false positive results of HE4. Smoking (OR 6.62 95% CI 2.93-15.12) and impaired renal function, measured by eGFR (OR 0.18 95% CI 0.08-0.39), were independently predictive of falsely elevated serum levels of HE4. Endometriosis was the only variable predictive of falsely elevated serum levels of CA125 (OR 7.96 95% CI 4.53-14.39). Age correlated with increased serum levels of HE4.
Conclusions:
Smoking, renal failure, age and endometriosis are factors that independently should be considered when assessing serum levels of HE4 and CA125 in women with an ovarian cyst or pelvic mass to avoid false indications of malignant disease.

