Can Endometriomas Produce Elevated CA-125 Markers?
Yes, endometriomas commonly produce elevated CA-125 levels, particularly in advanced endometriosis with cystic ovarian involvement, and this elevation should not automatically raise concern for malignancy in premenopausal women with clinical features consistent with endometriosis. 1
Mechanism and Patterns of CA-125 Elevation in Endometriosis
Source of CA-125 Production
- CA-125 is expressed by both normal (eutopic) and abnormal (ectopic) endometrial tissue, making endometriomas a direct source of this marker 2
- In women with cystic ovarian endometriosis (endometriomas), plasma CA-125 concentrations are markedly elevated 2, 3
- The elevation reflects the presence of endometrial-type tissue within the ovarian cyst wall that actively produces CA-125 2
Cyclic Variation in Endometriosis
- Women with advanced endometriosis show increased CA-125 concentrations toward the end of the luteal phase and during menstruation, but not during follicular and early luteal phases 2
- This cyclic pattern is not observed in women without endometriosis, making it a distinguishing feature 2
- Women with minimal or mild endometriosis typically show no elevation or only slight elevation in the luteal phase 3
Clinical Significance by Disease Severity
Marked Elevation in Specific Endometriosis Types
- Cystic ovarian endometriosis (endometriomas): Markedly elevated CA-125 levels are characteristic 2, 3
- Deeply infiltrating endometriosis: CA-125 can diagnose this condition with 36% sensitivity and 87% specificity, with particular utility for the most severe types (II and III) 2
- Minimal or mild endometriosis: CA-125 is typically not elevated or only slightly elevated, consistent with the concept that minimal disease may represent a normal intermittent condition rather than true disease 3
Extremely High Levels Can Occur
- Case reports document extremely elevated CA-125 levels (sometimes mimicking ovarian cancer levels) in patients with stage IV endometriosis and bilateral endometriomas 4, 5
- Leaking endometriomas can produce profoundly elevated CA-125 levels that might otherwise suggest malignancy 5
Diagnostic Utility of CA-125 in Endometriosis
Differentiating Endometriomas from Other Cysts
- Measurement of CA-125 in ovarian cyst fluid is the method of choice to differentiate a cystic corpus luteum from an ovarian endometriotic cyst 2
- This distinction addresses a frequent and difficult clinical problem in gynecology 2
Role in Unexplained Pelvic Pain
- CA-125 assay may be advocated in all women with unexplained pelvic pain as an aid in diagnosing deeply infiltrating endometriosis, given the strong association between deep endometriosis and pelvic pain 2
- The marker is particularly helpful as an additional parameter to diagnose "endometriotic disease" (deep endometriosis and cystic ovarian endometriosis) in patients with chronic pelvic pain 3
Monitoring Treatment Response
- Following surgical excision of endometriosis, CA-125 can monitor the completeness of surgery 2
- Elevated plasma CA-125 after treatment suggests incomplete treatment or disease recurrence 3
Critical Clinical Context: Avoiding Misinterpretation
Premenopausal Women with Suspected Endometriosis
- An elevated CA-125 in a premenopausal patient with an intermediate-risk lesion and clinical scenario highly suspicious for endometriosis should not unnecessarily elevate concern for malignancy 6, 1
- The American College of Radiology O-RADS committee emphasizes that tumor marker evaluation should be individualized, specifically acknowledging that endometriosis can cause CA-125 elevation that might otherwise suggest malignancy 6, 1
Multiple Tumor Markers May Be Elevated
- In addition to CA-125, endometriomas and leiomyomas can elevate CA 19-9 and chromogranin A (CgA) 7
- Some patients with endometriosis only have elevated CA 19-9 or CgA without CA-125 elevation 7
- Combined elevation of CA-125 and CA 15-3 has been reported in advanced endometriosis, though this is less common 4
Common Pitfalls to Avoid
False Reassurance in Postmenopausal Women
- A normal CA-125 level may provide false reassurance in a postmenopausal woman with an intermediate- or high-risk ovarian lesion (O-RADS 4 or 5) 6
- In postmenopausal women, the absence of functional ovarian activity means persistent masses warrant closer evaluation regardless of CA-125 levels 6
Other Benign Causes of Elevation
- CA-125 has limited specificity and can be elevated in pelvic inflammatory disease, adenomyosis, menstruation, other benign cysts, cirrhosis, and following radiotherapy 6, 8, 1
- Cirrhosis with ascites universally elevates CA-125 because mesothelial cells under pressure from fluid produce the antigen 8