The collateral damage of endometriosis: Increased risk of cancer, chronic pain and infertility

Research suggests that this chronic disease increases the likelihood of developing an ovarian tumor by up to three times

woman doctor gynecologist
A gynecologist examines a patient.Svetlana Repnitskaya (Getty Images)
Jessica Mouzo

Some diseases open the door to other ailments. On their own, they may not be lethal, but they increase the risk of developing other health problems and lower the patient’s quality of life. Endometriosis is a chronic disease that causes collateral damage that can threaten the patient’s life. This condition affects 10% of women of childbearing age; it occurs when endometrial tissue grows where it should not, causing severe pelvic pain during menstruation, when urinating or even when having sexual intercourse. It also causes fatigue, bloating, and nausea. In addition to all this, the ailment increases the risk of infertility, problems derived from chronic pain and even cancer. Recent research by scientists at the Hospital 12 de Octubre in Madrid, Spain, estimates that endometriosis increases the possibility of developing ovarian cancer by up to three times.

Endometriosis is a chronic and non-fatal disease, explains Mercedes Adeyro, the president of the Endoscopy Section of the Spanish Society of Gynecology and Obstetrics: “The disease occurs when the endometrium, which lines the uterine cavity, places cells outside the uterus. These cells can migrate through the Fallopian tubes, blood and lymph nodes. And they are placed in other places where they are not supposed to be, such as the peritoneum and the ovaries.” Symptoms depend on where these endometrial tissue cells end up being deposited. “There are mild forms of endometriosis, with almost no pain, and others that are severe, where patients really suffer,” she explains.

After many years of silence on this front, the scientific community is still scrutinizing the dimensions and particularities of this ailment. Francisco Carmona, the head of Gynecology at the Barcelona Hospital Clínic and an expert on endometriosis, points out that doctors still do not have “a reliable idea of the real prevalence” of the disease. “It still takes a long time to make a diagnosis. The disease is still in a very precarious situation because the symptomatology continues to be normalized and women who complain that they are in pain are stigmatized. Endometriosis does not just affect women during the childbearing years but lasts throughout their entire lives. In some cases, it does not end with menopause but can persist or start after that,” the gynecologist points out.

To demonstrate the severity of endometriosis and its impact on health, Carmona emphasizes that it is “a chronic inflammatory disease. Out-of-place endometria cause systemic, not local, chronic inflammation. It affects the whole body, which is conducive to comorbidities,” he notes.

In fact, the most characteristic symptom of endometriosis — intense pain — opens the door to other ailments. “Pain is a sensation created by the brain in response to potentially harmful stimuli. When pain persists without taking action to calm it down, it causes an inflammatory response at the peripheral level, which inflames the nerves and nerve receptors in that area; that ends up altering the functioning of the neurons in the central nervous system, in the cerebral cortex, and it starts to cause pain signals even though there is no harmful stimulus: pain ceases to be a symptom and becomes a disease,” Carmona explains. For that reason, some patients continue to feel pain even after operations are done to remove nodules in the abdominal cavity or pelvic regions, or even when the uterus is removed.

Myofascial syndrom e— very intense pain of muscular and fascial origin (the membrane covering the muscles) in the pelvis, abdomen and legs — is one type of collateral damage associated with endometriosis. Central sensitization syndromes, such as fibromyalgia, are another comorbidity, Carmona says: “The neurons respond poorly to stimuli that arrive there and produce hyperalgesia,” an increased sensitivity to pain and extreme reaction to it.

Endometriosis also raises the risk of autoimmune disorders, such as lupus or thyroid problems, and cardiovascular diseases. “Chronic inflammation is nothing more than the secretion of cells and substances to the rest of the body, and the immune system is also affected by this inflammation: it causes it to begin to weaken and fail,” explains the gynecologist at the Clínic. He adds that this inflammation “is also transmitted to the arteries and there are more cardiovascular events, such as heart attacks or strokes.” Infertility is also associated with endometriosis. “Thirty percent of women with endometriosis have trouble getting pregnant,” says Carmona.

An increased risk of ovarian cancer

Recent research by scientists at the Hospital 12 de Octubre in Madrid has also shown that endometriosis increases the risk of ovarian cancer. The study — which was presented last September at the Congress of the Spanish Society of Medical Oncology, but has not yet been published in a scientific journal — contributes additional evidence of something that the scientific community had already observed, explains Ainhoa Madariaga, an oncologist at the Gynecologic Tumors and Breast Unit of the 12 de Octubre Hospital and author of the study: “There’s already data that speaks to this association and, in fact, there is a meta-analysis that showed that the risk of ovarian cancer in women with endometriosis was twice as high as in the general population. [But] this meta-analysis had many biases and, in order to try to make the data we already knew about more robust, we did this study at a global level, using artificial intelligence and data from millions of patients.” Using real-life data from 128 million women, the researchers found “that the risk of ovarian cancer in those with a previous diagnosis of endometriosis was three times higher” than in the general population (those without endometriosis), Madariaga summarizes.

But the oncologist qualifies that the overall risk of developing this type of cancer among women with endometriosis “is low.” She notes that the study’s findings are “not at all alarming, because the risk is still low. The message should be to promote healthy lifestyle habits and continue to do periodic endometriosis check-ups, as recommended by your gynecologist.” Madariaga points out that the study also found that ovarian cancer associated with endometriosis is not the same as ovarian cancer in women who don’t have endometriosis: “[The cancer] seems to have a different biology. We saw that there were some rarer subtypes of ovarian cancer that were associated with endometriosis and also that it was diagnosed at earlier stages.” The researchers believe that this early detection is partly due to the fact that these are patients who are used to being more closely monitored and perhaps diagnosed earlier. But they also highlight that the biology of these patients’ cancer may be different. “We analyzed five-year survival rates and saw that the women who had ovarian cancer associated with endometriosis lived longer, which may be due to the biology of the disease or because it is diagnosed earlier.”

Carmona prefers not to evaluate the study until it is published in a scientific journal, but he says that “ovarian cancer is the cancer most associated with endometriosis, and it seems to have more pathogenic and genetic mechanisms.” However, he adds that the causes for that are not clear. “We have a lot of pieces of the puzzle, but we [still] don’t have the full picture. Inflammation in endometriosis seems to promote ovarian cancer, but we’re still looking for the mechanism through which benign cells become malignant.” Experts are studying whether there are altered genes or hormonal mechanisms that predispose patients to cancer.

However, Adeyro insists that “endometriosis usually does not result in ovarian cancer. Most patients with endometriosis will never develop ovarian cancer. There is a slightly increased risk, but the association between endometriosis and this cancer is small. Having a mother with ovarian cancer is a more powerful factor.” In any case, the member of the Spanish Society of Gynecology and Obstetrics recommends paying attention to the patients’ evolution, taking into account their age — postmenopausal women with endometriosis are at greater risk than young women — and monitoring imaging tests and tumor markers in the blood. Madariaga also reminds us that “having been on contraceptives reduces the risk of having ovarian cancer, which is important in the context of endometriosis, because contraceptives are used as a treatment” for this disease.

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