Endometriosis is a common, non-malignant condition where tissue resembling the lining of the uterus grows outside the womb, often affecting the ovaries and pelvic lining. This tissue responds to the menstrual cycle, leading to chronic inflammation, pain, and scarring in an estimated 10% of reproductive-aged women. Ovarian cancer, conversely, is a rare and serious malignancy characterized by the uncontrolled growth of abnormal cells in the ovaries or fallopian tubes. While these two conditions are fundamentally distinct, a growing body of epidemiological and molecular evidence suggests a connection between having endometriosis and a modestly increased risk for developing specific subtypes of ovarian cancer.
Statistical Connection: Which Cancers Are Implicated
Epidemiological studies consistently demonstrate that a diagnosis of endometriosis is associated with an elevated relative risk of developing ovarian cancer compared to the general population. The overall risk for any type of ovarian cancer in women with endometriosis is estimated to be approximately two to four times higher than in women without the condition. The baseline lifetime risk of ovarian cancer for the general female population is around 1.3%, rising to less than 2% for women with endometriosis.
The connection is highly specific to certain histological subtypes, particularly the epithelial ovarian cancers: Endometrioid Ovarian Carcinoma and Clear Cell Ovarian Carcinoma. These two types fall under the classification of Type I ovarian cancers, which tend to be slower-growing and diagnosed at an earlier stage than the more aggressive Type II cancers. The risk increase for Clear Cell Carcinoma, in particular, can be significantly higher, with some studies estimating it to be up to 11 times the risk of the general population.
The location and severity of the endometriosis lesions further refine this risk stratification. Patients with ovarian endometriomas, which are cysts filled with old blood located within the ovary, or deep infiltrating endometriosis show the most pronounced increase in risk. Women with these specific, more severe forms can have a risk of Type I ovarian cancer that is nearly 10 to 19 times greater than those without endometriosis. These findings suggest that the malignant transformation often begins directly within the ectopic tissue, particularly when it forms a cyst on the ovary.
Biological Bridges: Shared Risk Factors and Pathways
The link between endometriosis and ovarian cancer is thought to be a process of malignant transformation that occurs within the endometrial-like tissue itself, driven by a combination of factors. The chronic presence of ectopic endometrial tissue creates a unique microenvironment conducive to cellular change and the accumulation of genetic damage over time.
A central mechanism involves chronic inflammation and oxidative stress within the endometriotic lesions, especially in ovarian endometriomas. These cysts contain high concentrations of iron from repeated internal bleeding, which generates reactive oxygen species. This persistent chemical stress damages cellular DNA and promotes genome instability, providing the necessary environment for pre-malignant changes to occur. Inflammatory mediators, such as various cytokines, are also constantly released in the pelvic environment, acting as growth factors that encourage the proliferation and survival of abnormal cells.
Both endometriosis and the associated Type I ovarian cancers are considered estrogen-dependent conditions, indicating a shared hormonal influence on their development. Estrogen stimulates the growth and survival of the endometriotic cells, and this continuous hormonal stimulation can further drive the proliferative potential of genetically altered cells. The persistent exposure of the ectopic tissue to estrogen may contribute to the accumulation of cellular changes that eventually lead to malignancy.
At the molecular level, specific genetic alterations are frequently identified in both endometriotic tissue and the resulting Clear Cell and Endometrioid carcinomas. The most common mutation is the inactivation of the ARID1A gene, a tumor suppressor gene that plays a role in chromatin remodeling. Mutations in ARID1A are found in approximately 30% of endometrioid and over 50% of clear cell ovarian cancers, and this mutation is often present in the adjacent benign or atypical endometriotic lesions.
These ARID1A mutations frequently coexist with alterations in genes that regulate cell growth and survival, such as PTEN loss or activating mutations in PIK3CA. PTEN is a tumor suppressor that normally keeps the PI3K/AKT signaling pathway in check, and its loss or the activation of PIK3CA leads to uncontrolled cell proliferation and resistance to cell death. The sequential accumulation of these specific genetic changes is believed to represent the stepwise transition from benign endometriotic tissue to a fully malignant tumor.
Implications for Patient Monitoring and Risk Awareness
Given the established, albeit modest, increased relative risk, translating this information into clinical practice requires a balanced approach that focuses on awareness rather than universal aggressive screening. Routine population-wide screening for ovarian cancer in all patients with endometriosis is currently not recommended. This is primarily because the absolute risk remains low, and current screening tools, such as the blood test for the tumor marker CA-125, are often unreliable in this population.
The CA-125 protein is frequently elevated in women with benign endometriosis, giving the test low specificity that could lead to false-positive results and unnecessary invasive procedures. Therefore, medical guidance emphasizes a personalized approach centered on risk stratification and vigilant symptom awareness. Patients with the higher-risk subtypes of endometriosis, specifically ovarian endometriomas and deep infiltrating lesions, should be counseled about their slightly elevated risk.
For these higher-risk patients, regular monitoring, such as transvaginal ultrasound, may be considered, although the efficacy of this surveillance remains under investigation. The most important action for patients with a history of endometriosis is recognizing and reporting persistent, non-specific symptoms characteristic of ovarian cancer, such as persistent bloating, difficulty eating or feeling full quickly, and changes in urinary or bowel habits that are new, severe, and not related to the menstrual cycle. Consulting a physician about these concerning changes allows for a timely evaluation and can significantly improve the prognosis if a malignancy is detected.