Tumor Markers in Endometriosis Diagnostics

As you may be aware, various diagnostic techniques exist for identifying endometriosis. Typically, ultrasound provides an initial assessment, while laparoscopy is considered the gold standard. However, the ideal scenario would involve the swift and straightforward detection of endometriosis through a blood test, as is possible for many other diseases, including cancer, where tumor markers are frequently employed. In this article, we aim to explore the potential relevance of utilizing such tumor markers in the context of endometriosis diagnosis.

What Are Tumor Markers?

Tumor markers are biological substances produced either by a tumor itself or as a response from the body to cancer. They belong to the category of biomarkers, which find significant use in cancer diagnostics. Detectable in blood and other bodily fluids, these markers serve as valuable diagnostic tools.

While some tumor markers consistently exist within a normal range in the body, others are specific to cancer or other diseases. However, it is important to note that tumor markers are not standalone tests for cancer. Instead, they complement existing suspicions and provide information about the affected organ. Elevated marker levels can also indicate non-tumor-related conditions, such as inflammation. For instance, the tumor marker PSA (prostate-specific antigen) can be present in healthy individuals, but values should ideally remain below 4. Elevated values can suggest changes like prostate tumors. Nevertheless, the reliability of this marker is a topic of debate, as high values do not definitively indicate prostate changes. In contrast, the protein AFP (alpha-fetoprotein) is typically produced only by fetuses in the womb. Its presence in adults or children often signals liver or testicular cancer.

Tumor markers serve purposes beyond diagnosis. They are instrumental in assessing therapy effectiveness, making prognoses about disease progression, determining cancer stage, and predicting the likelihood of recurrence. For instance, circulating tumor cells (CTCs) in the blood predicts a less favorable prognosis, as it facilitates the formation of metastases—cancer cells spreading to other parts of the body. Metastasis indicates that cancer has spread beyond its original location. In ovarian cancer, monitoring CA-125 levels gauges the effectiveness of therapy [1], [2], [3].

Beyond their established roles, tumor markers are gaining significance in personalized medicine. Since tumors exhibit distinct characteristics in each individual, grow at varying rates, and respond differently to treatments, creating individualized profiles becomes crucial. Tumor markers aid in tailoring effective treatment plans, significantly enhancing treatment success rates, and saving valuable time by avoiding ineffective therapies [4].

Exploring Tumor Markers in Endometriosis Diagnosis

The quest for efficient, uncomplicated, and cost-effective methods of diagnosing endometriosis has been a long-standing endeavor in medicine. Given the success of various biomarkers in diagnosing other diseases, their potential application in endometriosis diagnosis is a logical area of exploration. Numerous studies have tackled this subject, yielding diverse findings.

One study in 1999 delved into the presence and concentration of multiple tumor markers in individuals with pelvic endometriosis lesions. The markers CA-125, CA-15-3, CA-19-9, CEA (carcinoembryonic antigen), AFP (alpha-fetoprotein), and B2MG (beta-2 microglobulin) were tested in 50 participants, categorized into two groups: healthy individuals (control group) and 35 endometriosis patients. Blood samples were collected during menstruation and one week later. The study revealed that only CA-125 exhibited elevated levels in individuals with stage 3 to 4 endometriosis, while other markers remained unremarkable across all 50 participants. Interestingly, blood samples taken during menstruation provided particularly informative data. It is noteworthy that CA-125 levels undergo slight increases during ovulation and slightly more during menstruation, which are normal fluctuations and not cause for concern [5].

A similar study conducted in 1997 extended the investigation to include the biomarker CRP (C-reactive protein) and CA-125, among others. CRP is of particular interest as an inflammation marker in the blood. This study corroborated the findings of the previous one, emphasizing CA-125’s potential significance in diagnosing endometriosis [7].

Both studies thus provided essential insights into the fact that the tumor marker CA-125 could be of interest for diagnosing endometriosis. However, only patients with endometriosis in the pelvic region were involved. However, it is essential to recognize that both studies primarily involved patients with pelvic endometriosis, and the sample size was relatively small, initially limiting their significance. Subsequent studies further explored this avenue.

In 2001, a study sought to determine whether elevated CA-125 levels could also be detected in peritoneal fluid within the abdominal cavity, expanding beyond the scope of previous studies that focused solely on blood samples. This study explored the potential of peritoneal fluid analysis for diagnosing endometriosis, particularly in its early stages. The investigation involved 107 participants, both with and without endometriosis, who underwent abdominal endoscopy during the menstrual cycle’s luteal or corpus luteum phase, spanning from ovulation to the onset of menstrual bleeding. The results were intriguing. Individuals with endometriosis exhibited elevated CA-125 levels in their peritoneal fluid, a finding that was consistent with expectations. However, this discovery was particularly noteworthy because of the significantly higher CA-125 levels in peritoneal fluid compared to blood samples and the early-stage elevation observed in stages 1 and 2 of endometriosis [8].

The study’s implications are promising, potentially simplifying the diagnostic process for endometriosis, especially in cases where endometriosis foci are challenging to detect during laparoscopy due to their concealed or petite nature. In the future, this research suggests that peritoneal fluid analysis and CA-125 testing could facilitate diagnosis even when visible endometriosis foci are absent.

2015, a comprehensive meta-analysis revisited the topic, reviewing studies conducted between 2000 and 2014. These studies focused on tumor markers CA-125, CA-19-9, and CA-15-3. CA-19-9 is typically elevated in various tumor diseases, including pancreatic, gastric, and ovarian cancers [9], while CA-15-3 is associated with breast cancer [10]. The meta-analysis evaluated 12 studies involving more than 1,000 individuals in which blood samples were analyzed for tumor markers. The meta-analysis encompassed 12 studies involving over 1,000 participants undergoing blood tests for tumor markers. The results corroborated earlier findings: CA-125 was significantly elevated in individuals with endometriosis, spanning the early and late stages of the disease. CA-19-9 also displayed associations with endometriosis, predominantly in late stages 3 and 4, with no significant changes in earlier stages. However, CA-15-3 did not appear to hold diagnostic relevance for endometriosis, with occasional elevation in later stages but without sufficient significance [11].

While the utility of CA-125 as a diagnostic tool for endometriosis appears promising, challenges remain regarding the precise threshold for diagnosis. Some studies suggest a diagnostic value above 30 U/ml (units per milliliter). However, it is crucial to recognize that a value below 30 U/ml does not rule out the presence of endometriosis. Moreover, distinctions between pre- and post-menopausal individuals have been noted, with a diagnostic value exceeding 37 U/ml for menstruating individuals and 35 U/ml for post-menopausal individuals. Further research is warranted to refine diagnostic criteria and better harness the potential of tumor markers in endometriosis diagnosis [12].

Conclusion: Can Endometriosis Detection Rely on Tumor Markers?

In summary, the utilization of tumor markers in endometriosis diagnosis and follow-up exhibits considerable promise. This research avenue may also detect possible malignant transformations at an earlier stage, provided that regular follow-up examinations are conducted. However, the ongoing debate surrounding the precise diagnostic thresholds remains a prominent challenge. Menstrual cycle-related fluctuations in tumor marker levels and varying interpretations among researchers contribute to the complexity of this issue. Consequently, it is premature to rely solely on determining tumor markers in blood or other bodily fluids to diagnose endometriosis. Nevertheless, the CA-125 marker can serve as a supportive tool when there is a suspicion of endometriosis. For instance, if individuals present typical symptoms and exhibit an elevated tumor marker level in their blood, these factors are important indicators of the condition’s presence. Nonetheless, abdominal endoscopy remains an essential diagnostic procedure, mainly because average marker values do not definitively rule out the presence of endometriosis. The integration of tumor markers as a standard diagnostic tool still requires extensive research and validation. While it is uncertain when or if tumor markers will replace the time-consuming laparoscopic procedures, their potential to do so remains an intriguing prospect, deserving of further investigation.


  1. Krebsinformationsdienst: Biomarker:Beispiele https://www.krebsinformationsdienst.de/untersuchung/molekulare-diagnostik/tumormarker-biomarker-beispiele.php (abgerufen am 24.03.2023)
  2. Die Techniker Krankenkasse: Was sind Tumormarker? https://www.tk.de/techniker/gesundheit-und-medizin/behandlungen-und-medizin/krebserkrankungen-oder-tumoren/was-sind-tumormarker-2018024 (abgerufen am 24.03.2023)
  3. National Cancer Institute: Tumor Markers https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet (abgerufen am 24.03.2023)
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  9. Öffentliches Gesundheitsportal Österreichs: CA 19-9 https://www.gesundheit.gv.at/labor/laborwerte/hormone-tumormarker/ca-19-9.html (abgerufen am 24.03.2023)
  10. Öffentliches Gesundheitsportal Österreichs: CA 15-3 https://www.gesundheit.gv.at/labor/laborwerte/hormone-tumormarker/ca-15-3.html (abgerufen am 24.03.2023)
  11. Shen A, Xu S, Ma Y, Guo H, Li C, Yang C, Zou S. Diagnostic value of serum CA125, CA19-9 and CA15-3 in endometriosis: A meta-analysis. J Int Med Res. 2015 Oct;43(5):599-609. doi: 10.1177/0300060515583076. Epub 2015 Aug 5. PMID: 26246541.
  12. Yonghua Chen, Meixia Pan, Ying Zuo, Bin Yang, Shaoguang Wang, Research progress of CA125 in endometriosis: Teaching an old dog new tricks, Gynecology and Obstetrics Clinical Medicine, Volume 2, Issue 4, 2022, Pages 191-198, ISSN 2667-1646, https://doi.org/10.1016/j.gocm.2022.10.006. (https://www.sciencedirect.com/science/article/pii/S2667164622000926)

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