Endometriosis is a common condition where tissue resembling the lining of the uterus grows outside the uterine cavity, often on the ovaries and fallopian tubes. This misplaced tissue responds to hormonal changes, leading to inflammation, pain, and scar tissue formation. Ovarian cancer involves the uncontrolled growth of abnormal cells in the ovaries or fallopian tubes, resulting in a malignant tumor. An association exists between these two distinct conditions, prompting investigation into how this benign chronic disease relates to a malignant one.
The Direct Relationship Between Endometriosis and Ovarian Cancer Risk
Research has established that women diagnosed with endometriosis carry a slightly elevated risk of developing ovarian cancer compared to the general population. The overall lifetime risk for women without endometriosis is approximately 1.3% to 1.4%. For those with endometriosis, this lifetime risk increases to about 1.8% to 1.9%, showing that the absolute increase in risk remains very small.
In relative terms, studies report that women with endometriosis have a 1.4- to 2-fold higher risk of ovarian cancer overall. This association is not uniform across all patients, but is most pronounced in those with specific, more severe forms of the condition.
Patients with ovarian endometriomas—cysts filled with old blood—or deep infiltrating endometriosis show the highest risk. For these specific, severe subtypes, the relative risk for certain cancers can be significantly higher, sometimes reported as nearly 10 times the risk of the general population. Despite these higher relative numbers, the overall probability of malignant transformation remains low, and the majority of women with endometriosis will never develop ovarian cancer.
Specific Ovarian Cancer Subtypes Linked to Endometriosis
The increased risk is not linked to all types of ovarian cancer but is highly specific to particular subtypes. The strongest association is with Endometrioid Ovarian Carcinoma and Clear Cell Ovarian Carcinoma. These two types are often categorized together as Endometriosis-Associated Ovarian Cancer (EAOC).
Clear cell and endometrioid carcinomas represent a minority of all ovarian cancers, distinguishing them from the more common and aggressive high-grade serous ovarian cancers. These EAOCs are often diagnosed at an earlier stage and tend to have a better prognosis than the high-grade serous subtype.
In pathological studies of EAOC cases, a significant proportion of tumors show concurrent endometriosis within the same ovary. This physical proximity supports the theory that the cancerous cells may have originated from the surrounding endometriotic tissue.
Underlying Biological Mechanisms of Malignant Transformation
The transition from a benign endometriotic lesion to a malignant tumor is driven by a sequence of molecular events, often starting in the ovarian endometrioma. One primary driver is chronic inflammation and resulting oxidative stress. The cystic fluid within endometriomas contains iron from degraded blood, which generates reactive oxygen species that damage cellular DNA.
This consistent DNA damage creates a mutational environment that can lead to the acquisition of specific genetic mutations. The most frequently identified genetic alteration in EAOCs is an inactivating mutation in the ARID1A gene. This tumor suppressor plays a role in chromatin remodeling and DNA repair, and its loss is an early event in the development of both clear cell and endometrioid carcinomas.
Another contributing factor is the hormonal environment of the ectopic tissue, which is exposed to high levels of estrogen. The endometriotic tissue itself can produce estrogen, and this localized hyperestrogenism promotes cell proliferation. The accumulation of these factors provides a plausible pathway for the malignant transformation of the endometriotic cells.
Monitoring and Clinical Management for Patients with Endometriosis
For patients with endometriosis, clinical management focuses on symptom control and awareness of health changes. Routine ovarian cancer screening using blood tests or transvaginal ultrasound is generally not recommended. This is because the absolute risk remains low, and screening has not been shown to improve outcomes in this population.
Patients should be educated about the subtle and persistent symptoms that may suggest ovarian cancer, which differ from the cyclical pain of endometriosis. These symptoms include persistent bloating, difficulty eating or feeling full quickly, or new or worsening abdominal or pelvic pain. Any such changes lasting more than a few weeks should be reported to a healthcare provider.
For patients with ovarian endometriomas, regular follow-up with imaging is common to monitor for suspicious changes, such as solid nodules within the cyst wall. Hormonal therapies, such as oral contraceptive pills used to manage endometriosis symptoms, are associated with a reduction in overall ovarian cancer risk. In rare, high-risk cases, a specialist may consider the surgical removal of large endometriomas, but this is a complex decision made individually.