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Fertility Drugs' Link to Ovarian Cancer Refuted

Review included 13,000 women in four countries

THURSDAY, Jan. 24, 2002 (HealthDayNews) -- Women who use fertility drugs to get pregnant can breathe a sigh of relief.

A new study -- the largest to date on the subject -- offers the best evidence yet that the popular medications used to increase the number of eggs a woman produces in a single monthly cycle do not increase the risk of ovarian cancer.

"While no one study ever provides a definitive answer, we are hopeful this large and detailed analysis will help lay to rest the notion that fertility drugs are in any way linked to ovarian cancer," says Dr. Roberta Ness, the study author and associate professor of epidemiology at the University of Pittsburgh's Graduate School of Public Health.

For Dr. Jaime Grifo, the finding is welcome news that has long been anticipated.

"We have always believed the drugs were safe, mainly because the original studies were flawed. They looked at only one population of women, those who were infertile. And we knew long before fertility drugs were being used that infertile women in general have an increased risk of ovarian cancer," says Grifo, director of the division of reproductive endocrinology at New York University Medical Center.

"I'm not surprised at all by this finding," adds Griffo, the newly elected president of the Society for Reproductive Technology. "But I am delighted that the study has been done and that women who have used or will use fertility drugs in the future will no longer have this needless worry."

The controversy over the link between fertility drugs and ovarian cancer developed about 10 years ago, when small, isolated pockets of women who had difficulty conceiving took fertility drugs and began developing ovarian cancer. Further studies explored the relationship with mixed results: some research showed a link; other studies failing to find one.

The new study, which involved almost 13,000 women from four countries, was a comprehensive analysis of a series of the most prominent studies on the subject. The study essentially threw out the findings of all the earlier studies and instead looked at the raw data used to arrive at study conclusions.

"Essentially, we re-analyzed all of the raw data from each of the studies much the way we would have if we had collected the information on our own," says Ness.

It was this giant re-analysis of massive amounts of information that found that women who took fertility drugs appeared to be at no greater risk for ovarian cancer than other women who had significant problems getting pregnant and did not take the drugs.

But while the study cleared fertility medications as a cause of ovarian cancer, infertility itself remains linked with the disease. According to the study results, at least one cause of fertility problems -- the menstrual-related disorder known as endometriosis -- could be a key factor.

"The study showed that women who have endometriosis were more likely to develop ovarian cancer," says Ness.

Endometriosis occurs when small bits of uterine lining meant to exit the body during the menstrual cycle instead migrate to various sites throughout the reproductive system, where they attach themselves and begin to grow.

Ness believes this process causes a kind of inflammatory reaction in the body that not only plays a key role in infertility, but may be the link to ovarian cancer as well.

Grifo partly agrees, but is not convinced that inflammation is the key.

"I think it is more likely that the endometriosis is mediating some type of immune system response that, in turn, is increasing the risk of ovarian cancer," he says.

The new study involved a collection of data on infertility and fertility-drug use from eight studies conducted between 1989 and 1999 in the United States, Denmark, Canada and Australia. It included 5,207 women with ovarian cancer and 7,705 women who were cancer-free.

The study defined infertility as "prolonged unsuccessful episodes of trying to conceive" and the necessity to seek medical help in conceiving.

After pooling and analyzing the raw data from each of the eight studies, the authors concluded that women who spent more than five years trying to get pregnant had a 2.7 fold increased risk of ovarian cancer when compared to women who tried less than one year to conceive.

Most important, says Ness, women who used fertility drugs were no more likely to develop ovarian cancer than those who did not use this type of medication.

The women in the study who were most likely to develop ovarian cancer were those suffering from endometriosis, or from "unknown causes" of infertility.

Other fertility-related factors found not to increase the risk of ovarian cancer included problems with ovulation or menstruation, ovarian cysts, blocked fallopian tubes, developmental problems within the uterus, cervical mucous problems or inflammation of the cervix.

The results will be published in the February issue of The American Journal of Epidemiology.

What To Do

To learn more about causes of infertility and available treatments, visit the American Society for Reproductive Medicine, or The International Council on Infertility Information Dissemination.

You can learn more about endometriosis by visiting The Endometriosis Association, or

SOURCES: Interviews with Roberta Ness, M.D., M.P.H., study author, associate professor of epidemiology, University of Pittsburgh Graduate School of Public Health; Jaime Grifo, M.D., director, Division of Reproductive Endocrinology, New York University Medical Center, and professor of obstetrics and gynecology, New York University School of Medicine, and president of Society for Assisted Reproductive Technology; February 2002 American Journal of Epidemiology
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