"For more than a decade, controversy has surrounded the relationships among infertility, fertility drug use and the risk of ovarian cancer," said Roberta Ness, M.D., M.P.H., associate professor of epidemiology at GSPH and principal investigator on the study. "This analysis helps put to rest the questions that have been troubling physicians and the women who endure arduous fertility treatments."
While no association was found between ovarian cancer and fertility drugs, the study does point out a link between ovarian cancer and certain specific causes of infertility -- namely, endometriosis and "unknown" reasons for infertility. The study suggests that some women who receive fertility treatments develop ovarian cancer because of underlying conditions that cause infertility, not because of the treatments themselves.
Investigators collected interview data on infertility and fertility drug use from eight case-control studies conducted between 1989 and 1999 in the United States, Denmark, Canada and Australia, including 5,207 women with ovarian cancer, and 7,705 women without ovarian cancer. In the study, infertility was signaled by prolonged unsuccessful episodes of trying to conceive, and by seeking medical help in conceiving.
Results showed that women who spent more than five years trying to conceive were at a 2.7-fold higher risk for ovarian cancer than those who tried for less than one year. Women who had used fertility drugs were not more likely to develop ovarian cancer than those who had never used fertility drugs. The risk of ovarian cancer dropped with each pregnancy.
Also, the infertile women who were most likely to develop ovarian cancer were those whose infertility resulted from endometriosis or from "unknown" causes.
Endometriosis is a condition in which cells from the uterine lining, or endometrium, migrate to various sites throughout the pelvis and attach to other organs, causing inflammation and pain, as well as infertility. In the newly published paper, Dr. Ness suggests that the local inflammation that is characteristic of endometriosis may play a role in ovarian cancer. Conversely, researchers are as yet unsure how to characterize "unknown" causes of infertility.
"We are actively working to better understand what are now unknown causes of infertility," said Dr. Ness. "Understanding this better will give us a window into the biology behind ovarian cancer and it will help to define the women in this high-risk group."
Researchers found that ovarian cancer was not associated with the following causes of infertility: ovulation or menstrual problems, ovarian cysts, blocked tubes, uterine development problems or cervical mucous and/or inflamed cervix.
Women who took fertility drugs but never became pregnant were more likely to have non-invasive tumors, according to the study, but the researchers suggest that more tumors were found among these women because they were under intense medical scrutiny while undergoing fertility treatment.
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