Western Regional Blog – BC, YK, AB, NWT and Nunavut
Is There a Link Between Endometriosis and Ovarian Cancer?
Peter Kovacs, MD, PhD
Buis CC, van Leeuwen FE, Mooij TM, Burger CW; OMEGA Project Group / Hum Reprod. 2013;28:3358-3369
A woman has a 1:70 risk of being diagnosed with ovarian cancer in her life. Early-stage disease is usually asymptomatic, and unfortunately, there are no effective screening tools. Ovarian cancer, therefore, is often diagnosed at an advanced stage, when treatments have limited efficacy.
There are several theories regarding the etiology of ovarian cancer.[2-4] Certain reproductive factors (early menarche, late menopause, low parity, infertility) are associated with increased risk. The most widely accepted theory explains the origin of ovarian cancer by the repeated epithelial trauma accompanying ovulations. The surface trauma is followed by repair, during which mutations could occur, resulting in malignant transformation.
The gonadotropin theory attributes a role to elevated levels of gonadotropins in inducing malignant changes. Another theory posits a role of androgen hormones in the induction of ovarian cancer. Some groups consider ovarian cancer to be the result of inflammatory changes, which can be induced by endometriosis.
Ovarian cancer and fallopian tube cancer often coexist; this raises the possibility that these epithelial cancers originate from the tube. Carriers of certain mutations (BRCA1 and BRCA2) are also at a higher risk of developing ovarian cancer.
Infertile women are often nulliparous or have low parity, may have abnormally elevated gonadotropin/androgen levels, and usually require stimulation that will induce multiple ovulations as part of their treatment. In addition, many of them are affected by endometriosis. It is not surprising, then, that many researchers have shown an interest in a potential link between ovarian cancer and various aspects of infertility and its treatment.
The OMEGA Project Group aimed to investigate the late effects of hormones. This current subgroup analysis evaluated the risk for ovarian cancer among women with endometriosis. Over 19,000 women who had undergone in vitro fertilization (IVF) were enrolled in the OMEGA study between 1980 and 1995. The controls included 6604 women with a diagnosis of infertility who had not received IVF treatment. Data were collected from questionnaires, by checking medical records, and by linking to a histology database and cancer registry.
Researchers enrolled 2851 women with histologically or surgically confirmed endometriosis and 806 women self-reporting endometriosis as the cause of infertility. Controls included 5247 women without any evidence for endometriosis. During the analysis, age, contraceptive pill use, parity, and IVF exposure were controlled for. The median follow-up was 15.2 years.
The main analysis included cases in which endometriosis had been diagnosed before the diagnosis of ovarian tumor was made. Twenty-six cases (16 cancers and 10 borderline tumors) were diagnosed in the endometriosis group, and 5 (2 cancers and 3 borderline tumors) were diagnosed in the control group (hazard ratio [HR], 8.2; 95% confidence interval [CI], 3.1-21.6). The risk remained similar after adjustments were made for age, oral contraceptive use, parity, and IVF treatment. Women who were exposed to oral contraceptives for more than 5 years had only a nonsignificant elevation in ovarian cancer risk (HR, 2.7; 95% CI, 0.7-10.4). In contrast, those with less than 5 years of oral contraceptive use were at an increased risk (HR, 6.8; 95% CI, 2.3-20.5).
This study found an increased risk for ovarian cancer among infertile women with endometriosis. Endometriosis can be diagnosed in about 10%-15% of women and in 30%-40% of the infertile population. Therefore, a 3- to 8-fold increased risk, even if based on relatively few cases, is significant.
Many groups looked for an association between ovarian cancer and fertility treatment. The results so far have been mostly reassuring. Compared with the general population, a slightly increased risk was seen among those with infertility who had been exposed to treatment, but the risk was primarily limited to nulliparous women. Within the infertile cohort, the use of gonadotropins typically was not associated with an increased risk compared with those not exposed.[7-9] Most studies suffer from methodological issues, such as lack of controlling for confounding variables, short follow-up, a limited number of cancer cases, and incomplete data collection.
Endometriosis is known to be associated with inflammatory changes that could induce malignant changes. Endometriosis is often associated with infertility and nulliparity could further increase the risk. One of the strengths of the current study is that most endometriosis cases were confirmed by operative or histology reports. Women who self-reported endometriosis without surgical confirmation were also enrolled, but excluding them from the analysis would not have significantly changed the direction of the associations.
Contraceptive pills are often used to manage the various problems associated with endometriosis. In this study, women who took oral contraceptives for more than 5 years were at lower risk of developing ovarian cancer. Oral contraceptive use is known to be associated with an up to 50% risk reduction for ovarian cancer. It appears that a similar beneficial effect can be seen among those with endometriosis. This benefit should further be explored.
Many women with endometriosis require surgery to manage their symptoms; this may involve ovarian surgery, or potentially, oophorectomy. This certainly would have a significant impact on their future ability to conceive. On the basis of the findings of the current study, infertile women with endometriosis are at an increased risk for ovarian cancer. One could consider elective oocyte or embryo cryopreservation to allow them to maintain fertility, should radical surgery be needed to manage their symptoms