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The risk of developing ovarian cancer appears to be fourfold increased in women with endometriosis, compared to women who have not been diagnosed with the disease, according to a new study.
Scientists know that endometriosis may be linked to an increased risk of ovarian cancer, but the study details how that risk may vary across endometriosis subtypes.
Endometriosis is a common and often painful condition that occurs when tissue similar to the lining of the uterus grows outside the uterus itself. It is estimated to affect more than 11% of women aged 15 to 44 in the United States.
Women with severe forms of endometriosis (deep endometriosis, ovarian endometriomas, or both) have a “significantly increased” overall risk of ovarian cancer, about 9.7 times higher, compared with women without endometriosis, according to the study published Wednesday in the medical journal JAMA. Deep-seated endometriosis is found deep within the tissue or organ, and ovarian endometriomas, sometimes called “chocolate cysts,” are cysts that form in the ovary.
Women with deep infiltrating endometriosis, ovarian endometrioma, or both appear to face a nearly 19-fold increased risk of type I ovarian cancer, which tends to grow more slowly, compared with women without endometriosis, the study found.
But people with endometriosis shouldn’t panic over the new study’s findings, experts say, because ovarian cancer itself is still rare.
According to the National Cancer Institute, about 1.1% of American women will be diagnosed with ovarian cancer at some point in their lives. This year, it is estimated that there will be nearly 20,000 new cases of ovarian cancer and about 13,000 people will die from the disease.
“It is worth noting that because of the rarity of ovarian cancer, the association with endometriosis only increases the number of cancer cases by 10 to 20 per 10,000 women,” said Karen Schliep, lead author of the new study and associate professor in the Division of Public Health at the University of Utah School of Medicine.
“We are not recommending, at this time, any changes in clinical care or policy,” she added. “The best way to prevent ovarian cancer remains to recommend physical exercise, not smoking, and limiting alcohol consumption.” In addition to age, a family history of ovarian cancer, breast cancer, or colorectal cancer is also a significant 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, wrote in an email BJ Rimel, MD, a gynecologic oncologist and medical director of the Cancer Clinical Trials Office at Cedars-Sinai, who was not involved in the study.
“If someone has endometriosis and their doctor has recommended that they take oral contraceptive pills, whether it’s to treat their condition or just for contraception, I think it’s definitely possible to take them,” Rimel said. “Oral contraceptive pills are associated with a 50 percent reduction in the risk of ovarian cancer, which is great news.”
For the new study, a team of researchers in the United States analyzed data from nearly 500,000 Utah women aged 18 to 55. The data came from the Huntsman Cancer Institute’s Utah Population Database, and the researchers looked closely at the number of women identified as having endometriosis in their electronic medical records as well as the number of women who developed ovarian cancer between 1992 and 2019, based on the Utah Cancer Registry.
The researchers found that the risk of all types of ovarian cancer was 4.2 times higher in women with endometriosis than in women without the disease. The risk of type I ovarian cancer was “particularly high,” the study found, at about 7.5 times higher in women with endometriosis, and the risk of developing type II ovarian cancer — which can be more aggressive — was about 2.7 times higher.
“The magnitude of these associations varied by endometriosis subtype. Individuals diagnosed with deep infiltrating endometriosis and/or ovarian endometriomas had a 9.66-fold increased risk of ovarian cancer compared with individuals without endometriosis,” the researchers wrote.
The researchers found that, compared with women without any type of endometriosis, women with deep infiltrating endometriosis had the highest risk of ovarian cancer overall — about 18.8 times higher — and women with deep infiltrating endometriosis associated with ovarian endometriomas had the second highest risk, about 13 times higher.
These dramatic increases surprised Schliep and his colleagues.
“As an epidemiologist, you don’t always see that kind of relationship, where you see a tenfold increase in risk, with pretty tight confidence intervals of eight to 12 times, and then a 19-fold increase in risk,” Schliep said. “That’s what shocked me, just from an epidemiology perspective.”
The study data did not report which women with endometriosis were treated specifically with oral contraceptives or gonadotropin-releasing hormone agonists, which could slightly skew the data because birth control pills are associated with a lower risk of ovarian cancer and it is still unclear what associations gonadotropin-releasing hormone agonists may have with cancer risk. Additionally, some women listed as not having endometriosis in the data may have been undiagnosed or misdiagnosed.
But overall, the study adds to the body of research suggesting a link between endometriosis and ovarian cancer risk, wrote Dr. Michael McHale of the University of California, San Diego, in an editorial accompanying the new study in JAMA.
“Furthermore, these data support the importance of counseling women with deep endometriosis and/or ovarian endometriosis regarding the increased risk of ovarian cancer. Although the absolute number of ovarian cancers is small, the increased risk is significant,” he wrote. “In women who are finished with children or have other fertility options, more definitive surgery should be discussed and considered. As always, shared decision-making is essential given the evolving data.”
The new study shows the strongest association yet between endometriosis and ovarian cancer risk, said Dr. Tatnai Burnett, a minimally invasive gynecologic surgeon at the 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 abnormal proliferation of cells – in endometriosis, for example, you see cells where they’re not supposed to be – is a genetic phenomenon. Cells acquire the ability to move or be in one place, and there’s probably a genetic relationship between these phenomena,” Burnett said.
“But there are a multitude of other potential links, ranging from inflammatory links to immunological factors,” he said. “There are multiple potential associations, so I don’t think we can effectively guess at any one thing.”
However, people with endometriosis shouldn’t panic about this association, Burnett said.
“The risk remains lower overall than that of cancer,” he said. “Currently, even with the known risk levels, we have not recommended universal screening for patients with endometriosis, and I don’t think that will necessarily change. We already follow women with endometrioma or cystic endometriosis with ultrasound, to rule out the development of malignancy. So I don’t think this will change our recommendations at this point.”
Endometriosis itself is a diagnosis that is not fully understood, which also makes it difficult to fully understand the association with ovarian cancer, said Dr. Deanna Gerber, a gynecologic oncologist at the Perlmutter Cancer Center at NYU Langone-Long Island Hospital in New York City, who was not involved in the new study.
There could be a genetic factor behind this association, or the inflammation often seen with endometriosis could increase the risk of ovarian cancer, she said, but hormonal factors could also be behind the association.
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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 percent, which is much lower than the risk of a common cancer like breast cancer,” Gerber said. “So in the study, a four-fold increased risk of ovarian cancer still keeps women at very low risk.”
The new study shows an association between endometriosis and ovarian cancer, but not causation – and exactly what drives that association remains unclear, Cedars-Sinai’s Rimel says.
“Several mechanisms have been proposed, but none are completely proven. Some mutations in genes such as ARID1A are associated with endometriosis and endometrial cancer, which could link the two,” Rimel wrote in an email.
She added that another possible mechanism could involve how endometriosis forms and how that formation can damage tissue, creating a more cancer-friendly environment – but more research is needed.