Using an intrauterine device (IUD) for contraception was associated with a lower risk of developing ovarian cancer, according to a systematic review and meta-analysis of existing retrospective data. There was a 32% reduction in ovarian cancer risk among women who had ever used an IUD compared with never users. The finding confirms results of other, smaller studies, senior author Saketh Guntupalli, MD, director of gynecologic oncology at the University of Colorado School of Medicine and UC Health Hospital, Denver, told Medscape Medical News. "This is the first meta-analysis or large grouping of data that show that, potentially, women who use an IUD for birth control instead of oral contraception have a reduced risk of developing ovarian cancer later in life," Guntapalli said. "Women who have a higher risk of ovarian cancer, or who are worried about ovarian cancer, might choose the IUD for contraception, and we think that these data will provoke a discussion of its merits," he said. However, another expert noted that oral contraceptive pills are already known to reduce the risk of ovarian cancer, by about 50%. Guntapali added that he hopes that this new study "will prompt talks between women and their health care providers about what method of birth control is best for them." The review was published online September 10 in Obstetrics & Gynecology. For their study, Guntupalli and colleagues searched MEDLINE, EMBASE, Cochrane Library, and Web of Science Core Collection databases from inception to June 2018. They identified 564 reports of an association between IUD use and ovarian cancer, but eliminated the vast majority of them because they were case reports or had other limitations. Ultimately, they decided to use 11 studies for the meta-analysis. Of these, 9 were case control studies with a total of 4484 incident cases of ovarian cancer and 9107 women who did not have a diagnosis of ovarian cancer. When considering the case-control studies separately from the cohort studies, the summary odds ratio (OR) association between "ever use" of an IUD and incident ovarian cancer was 0.68 (95% confidence interval [CI], 0.55 - 0.85). The two cohort studies included data from 649 patients with ovarian cancer, compared with 173,928 women not diagnosed with ovarian cancer. The summary OR for ovarian cancer among women who used an IUD was 0.66 (95% CI, 0.52 - 0.84). How Is an IUD Protective? There are two different kinds of IUDs: one is hormonal and the other is metal, Guntupalli explained. The levonorgestrel IUD uses a progesterone to prevent pregnancy. Progestins have an anti-estrogenic effect and this effect is thought to reduce the risk of ovarian cancer. The copper IUD causes a low-grade inflammatory response within the female reproductive tract. "New data shows that immune cells are very much involved in cancer surveillance and cancer screening within the host. As a result, we think that those immune cells may be killing off the precancerous cells," he said. An important limitation of the review is the lack of data on duration of IUD use. "How long does a woman need to use an IUD for her risk to be reduced? Unfortunately, we could not answer that question in our review. There was no temporal relationship that we were able to abstract," Guntupalli said. Approached for comment, Gary S. Leiserowitz, MD, chair of the Department of Obstetrics and Gynecology at University of California Davis School of Medicine in Sacramento, told Medscape Medical News that how an IUD protects against ovarian cancer is really not known. "The possible mechanisms they suggest in the paper are all speculative," Leiserowitz said, "because, to my knowledge, nobody knows. "One of the possibilities here is that some women who have IUDs may not ovulate consistently, which is probably the mechanism by which oral contraceptives decrease the risk of ovarian cancer. It has been known for a long time that the use of oral contraceptives has been associated with a 50% decreased risk of developing ovarian cancer, and it has also been known that tubal ligation also decreases the risk of ovarian cancer." Leiserowitz, who was not involved with the review/meta-analysis, agreed that the lack of data about duration of IUD use is an important issue. "One of the things that happens when you do these association studies is trying to understand the dosage relationship," he explained. "These studies don’t give you that information." Leiserowitz agreed with Guntupalli that he would like to see IUDs mentioned as an option for birth control. "We currently have discussions with patients about use of oral contraceptives in an attempt to decrease their risk of developing ovarian cancer. So, especially in women who have a known genetic mutation, like BRCA1 and BRCA2, if they are not yet ready to have risk-reduction surgery, use of an IUD could be mentioned, either before or in between pregnancies," he said. Guntupalli and Leiserowitz have disclosed no relevant financial relationships. Obstet Gynecol. Published online September 10, 2019. Abstract Source
