Women with endometriosis face fourfold higher risk of ovarian cancer, study suggests
Scientists have known that endometriosis may be linked with an increased ovarian cancer risk, but the study details how that risk can vary by subtypes of endometriosis.
Endometriosis is a common and often painful condition that happens when tissue similar to the lining of the uterus grows outside the uterus itself. It’s estimated to affect more than 11% of women between the ages of 15 and 44 across the United States.
Women with severe forms — either deep infiltrating endometriosis, ovarian endometriomas or both — have an overall ovarian cancer risk that’s “markedly increased,” at about 9.7 times higher, relative to women without endometriosis, according to the study, published Wednesday in the medical journal JAMA. The form of endometriosis that is deeply infiltrating is found deep within the tissue or organ and ovarian endometriomas, sometimes called “chocolate cysts,” are cysts that form in the ovary.
And women with deep infiltrating endometriosis, ovarian endometriomas or both appear to face nearly 19 times the risk of type I ovarian cancer, which tends to grow more slowly, compared with women without endometriosis, according to the study.
But people with endometriosis should not panic about the new study findings, experts say, because ovarian cancer itself is still rare.
About 1.1% of US women will be diagnosed with ovarian cancer at some point in their lifetime, according to the National Cancer Institute. This year, it is estimated that there will be nearly 20,000 new cases of ovarian cancer, and about 13,000 people will die of the disease.
“It should be noted that, because of the rarity of ovarian cancer, the association with endometriosis only increased the number of cancer cases by 10 to 20 per 10,000 women,” said Karen Schliep, senior author of the new study and an associate professor in the Division of Public Health at the University of Utah School of Medicine.
“We would not recommend, at this point, any change in clinical care or policy,” she added. “The best way of preventing ovarian cancer is still the recommendation of exercise, not smoking and limiting alcohol.” Other than age, having a family history of ovarian cancer, breast cancer or colorectal cancer is also an important risk factor for ovarian cancer.
Overall, people with endometriosis should be aware of the warning signs of ovarian cancer, including bloating, abdominal pain and changes in bowel or bladder function, Dr. BJ Rimel, a gynecologic oncologist and medical director of the Cancer Clinical Trials Office at Cedars-Sinai, who was not involved in the study, wrote in an email.
“If a person has endometriosis and oral contraceptive pills have been recommended by their doctor for either treatment or for just plain old contraception, then I would definitely consider taking them,” Rimel said. “Oral contraceptive pills are associated with a 50% risk reduction of ovarian cancer which is great news.”
Researchers find ‘shocking’ increases
For the new study, a team of researchers in the United States analyzed data on nearly 500,000 women in Utah, ages 18 to 55. The data came from the Utah Population Database at the Huntsman Cancer Institute, and the researchers took a close look at how many women were identified as having endometriosis in their electronic health records as well as how many developed ovarian cancer between 1992 and 2019, based on the Utah Cancer Registry.
The researchers found that the risk of all ovarian cancer types was 4.2-fold higher among women with endometriosis than in women without the condition. The risk of type I ovarian cancer specifically was “especially high,” according to the study, at around 7.5-fold higher among women with endometriosis, and the risk of developing type II ovarian cancer – which can be more aggressive – was about 2.7 times more likely.
“Magnitudes of these associations varied by endometriosis subtype. Individuals diagnosed with deep infiltrating endometriosis and/or ovarian endometriomas had 9.66 times the risk of ovarian cancer when compared with individuals without endometriosis,” the researchers wrote.
The researchers found that, relative to women without any type of endometriosis, women with deep infiltrating endometriosis had the highest risk of ovarian cancer overall — around 18.8 times higher — and women with deep infiltrating endometriosis along with ovarian endometriomas had the second-highest risk, about 13-fold higher.
Those dramatic increases were surprising to Schliep and her colleagues.
“To see this jump tenfold, with fairly tight confidence intervals between eightfold and 12-fold, and then a 19-fold higher risk, as an epidemiologist, you don’t always see those types of relationships,” Schliep said. “That’s the part that was shocking to me, just from an epidemiology point of view.”
The study data did not indicate which women with endometriosis were treated specifically with oral contraceptives or with gonadotropin-releasing hormone agonists, which could slightly skew the data, as birth control pills are associated with a lower risk of ovarian cancer and it remains unclear what associations gonadotropin-releasing hormone agonists may have with cancer risk. Additionally, some women indicated as not having endometriosis in the data could have been undiagnosed or misdiagnosed.
But overall, the study adds to the body of research suggesting a link between endometriosis and ovarian cancer risk, Dr. Michael McHale of the University of California, San Diego, wrote in an editorial accompanying the new study in JAMA.
“Moreover, these data support the importance of counseling women with deep infiltrating and/or ovarian endometriosis regarding the increased risk for ovarian cancer. Although the absolute number of ovarian cancers is limited, the increased risk is significant,” he wrote. “In those women who have completed childbearing or have alternative fertility options, consideration for more definitive surgery should be discussed and considered. As always, shared decision-making is essential given these evolving data.”
‘Risk is, overall, still on the lower side’
The new study shows the strongest association to date between endometriosis and ovarian cancer risk, said Dr. Tatnai Burnett, a minimally invasive gynecology surgery specialist at Mayo Clinic in Rochester, Minnesota, who was not involved in the research but whose work focuses on endometriosis.
He added that this association could be driven by a number of factors.
“We know that an abnormal proliferation of cells — so in endometriosis, we’re seeing cells where they’re not supposed to be — and that’s a genetic phenomenon. Cells gain the ability to move or be in places, and there probably is some relationship there genetically,” Burnett said.
“But then there’s a host of other potential connections, from inflammatory connections to immunological factors,” he said. “The are multiple potential associations, so I don’t think we can effectively guess at one particular thing.”
Still, people who have endometriosis should not panic about the association, Burnett said.
“The risk is, overall, still on the lower side of cancer risks,” he said. “Currently, even with the known risk levels, we haven’t recommended any universal screening for patients with endometriosis, and I don’t see that necessarily changing. We already do follow women with endometriomas or cystic endometriosis with ultrasound, to rule out the development of malignancy. So I don’t see this changing our recommendations at this point.”
Endometriosis itself is a diagnosis that’s not fully understood, which makes the association with ovarian cancer difficult to completely comprehend as well, said Dr. Deanna Gerber, a gynecologic oncologist at the Perlmutter Cancer Center at NYU Langone Hospital–Long Island in New York, who was not involved in the new study.
There could be a genetic factor driving the association, or the inflammation that is often seen with endometriosis could increase ovarian cancer risk, she said, but hormonal factors could be driving the association, as well.
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Patients should remember that “the risk of ovarian cancer is extremely low in the general population. It’s less than 2%, which is much, much less than a common cancer like breast cancer,” Gerber said. “So, in the study, a fourfold increased risk in ovarian cancer still keeps women at a very low risk.”
The new study demonstrates an association between endometriosis and ovarian cancer but not causation – and what exactly drives that association remains unclear, according to Rimel of Cedars-Sinai.
“There are several proposed mechanisms but none are completely proven. Some mutations in genes such as ARID1A are associated with endometriosis and endometrial cancer, which may link the two,” Rimel wrote in an email.
She added that another possible mechanism could involve the way in which endometriosis forms and how that formation may damage tissue, creating a more prone environment for cancer — but more research is needed.
Despite the increased ovarian cancer risk associated with certain subtypes of endometriosis, it's important to note that ovarian cancer itself is still relatively rare. According to the National Cancer Institute, only about 1.1% of US women will be diagnosed with ovarian cancer during their lifetime.
Regular exercise, not smoking, and limiting alcohol consumption are still recommended as the best ways to prevent ovarian cancer, and having a family history of ovarian, breast, or colorectal cancer is an important risk factor for the disease.
