Endometriosis and Ovarian Cancer Risk: Clinical and Molecular Insights

A systematic review published in Gynecologic Oncology finds a modest but statistically significant link between endometriosis and an increased risk of ovarian cancer, specifically the endometrioid and clear cell subtypes. While relative risk increases—ranging from 1.3 to 4.2—the absolute lifetime risk remains low, rising from approximately 1.4% in the general population to about 1.9% for women with endometriosis.

Why does endometriosis increase the risk of ovarian cancer?

The connection is multifactorial, rooted in chronic inflammation and hormonal imbalances. According to the review in Gynecologic Oncology, a hormonal environment dominated by estrogen and lacking progesterone promotes cellular survival and genetic instability.

Chronic inflammation increases cytokine production and oxidative stress, often induced by iron deposits. This process can lead to DNA damage and abnormal cell proliferation, which may facilitate malignant transformation.

Molecular evidence shows shared mutations in genes such as ARID1A, PTEN, and PIK3CA in both endometriotic and neoplastic tissues. Atypical endometriosis, marked by cellular atypia or glandular proliferation, is recognized as a possible precursor lesion for malignancy.

Did You Know? Endometriosis is a chronic, estrogen-dependent disease that affects approximately 1 in 8 women of reproductive age worldwide.

How high is the actual risk for patients?

The study, which analyzed 35 English-language papers published between January 2000 and October 2025, highlights a critical difference between relative and absolute risk. Relative risks varied between 1.3 and 4.2, with some severe disease subgroups showing up to a 10-fold increase.

The highest risks are typically observed in women with deep infiltrating endometriosis or ovarian endometriomas. Despite these relative spikes, the absolute risk of developing ovarian cancer over a lifetime only increases by about 0.5% compared to the general population.

Expert Insight: Samantha Carter notes that the medical community must carefully communicate the gap between relative and absolute risk. Overemphasizing relative risk can trigger excessive patient anxiety and lead to “medicalization,” where patients undergo unnecessary tests or surgeries that offer little clinical benefit.

What changes in medical care and screening?

The review concludes that there is insufficient evidence to justify routine oncological surveillance or prophylactic surgery based solely on an endometriosis diagnosis. While biomarkers like HE4, CA-125, and the ROMA algorithm can be helpful, their current role is limited.

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Clinical focus may shift toward individualizing risk. Women with atypical endometriosis, deep infiltrating disease, or large ovarian endometriomas could require more tailored monitoring.

Additionally, the prolonged use of hormonal contraceptives, used both for symptom management and the prevention of endometrial cancer, appears to exert a protective effect against ovarian cancer.

What may happen next for patients?

Future clinical models may be developed to identify specific subgroups of patients with a higher predisposition to malignancy. This could lead to more precise screening protocols for those with the most severe forms of the disease.

Physicians are likely to emphasize a balanced approach to counseling, ensuring patients understand that the majority of women with endometriosis will never develop ovarian cancer.

Frequently Asked Questions

Does a diagnosis of endometriosis mean I will develop ovarian cancer?
No. The absolute risk remains low, increasing from about 1.4% in the general population to approximately 1.9% for those with endometriosis.

Which types of ovarian cancer are most associated with this condition?
The association is strongest with the clear cell and endometrioid histological subtypes.

Is routine screening recommended for all women with endometriosis?
No, the current evidence does not justify systematic oncological screening or routine prophylactic surgery for all patients.

How do you balance the need for medical vigilance with the goal of avoiding unnecessary health anxiety?