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Fertility Drugs and Ovarian Cancer Not Linked, Study Says
One of the largest studies to explore whether fertility drugs increase a woman’s risk of ovarian cancer found “no convincing association” with the cancer, though researchers said they would continue to follow tens of thousands of Danish women to see if their risk increased with age.
The generally reassuring results were consistent with several other recent studies, which have tempered an initial panic set off in the 1990s when reports suggested that the widely used fertility drugs might lead to a surge in a cancer that is relatively uncommon but often fatal.
The new study, published online Thursday in the British Medical Journal, did not rule out a cancer link altogether. It suggested that the risk of one form of ovarian cancer may be elevated after use of the popular drug clomiphene (brand name Clomid), though researchers said the finding could have been a statistical aberration.
“The message to give clinicians and patients is that over all these data provide further evidence that fertility drugs do not increase the risk of ovarian cancer to any great extent,” said Allan Jensen, an assistant professor of cancer epidemiology at the Danish Cancer Society and the first author of the paper. The senior author was Susanne Krüger Kjaer.
Dr. Jensen added, “You should always balance a possible small increase in ovarian cancer risk with the physical and psychological benefits of pregnancy made possible only by use of these drugs.”
As part of the study, the researchers followed 54,362 women who had been referred to Denmark’s fertility clinics between 1963 and 1998. They gathered information about the women from Denmark’s birth, cancer and hospital discharge registries, seeking more detailed information on medications from individual medical records of a subgroup of 1,241 of the women.
Among the 54,362 infertile patients followed for an average of 15 years, there were 156 cases of ovarian cancer. The average age of the women by the end of the study was 47.
Medical records were used to analyze the relative risk of ovarian cancer in women who had taken either gonadotropins, clomiphene citrate, human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone, compared with ovarian cancer rates of women who had not taken each of the individual drugs (but may have been treated with one of the other medications).
After adjusting for risk factors, the researchers concluded there was no increase in ovarian cancer risk associated with the drugs, nor was there an increased risk for women who underwent 10 or more cycles of treatment or for women who never became pregnant despite treatment.
The only statistically significant increase was seen in an analysis looking at different types of ovarian cancer tumors; in that analysis, women who had taken clomiphene citrate had a 67 percent increase in serous ovarian cancer tumors.
A separate analysis comparing women who had used a fertility drug with women who had not used any of the drugs also found no significant differences, Dr. Jensen said, but those figures were not included in the paper. There was also no difference in risk for women who had used a combination of fertility drugs.
The research in this area is complicated by the fact that infertile women appear to be at higher risk for ovarian cancer to begin with, which is why this study compared infertile women with one another rather than with other women in the population. In addition, because ovarian cancer is quite rare, large populations must be studied to obtain meaningful results.
The scientists cautioned that the women in the study would have to be followed for many more years to see if their risk increased over time. The mean age for diagnosis of ovarian cancer in women is 63.
“This is the largest study to look at ovarian cancer and they’re right, it’s a major strength of the study,” said Louise Brinton, the chief of the National Cancer Institute’s hormonal and reproductive epidemiology branch, adding that she was surprised the authors played down the finding of an association between Clomid and serous ovarian cancer, which may be more influenced by hormonal factors than some other tumors. Clomid is one of the older drugs in use.
Dr. Roberta Ness, dean of the University of Texas School of Public Health and the author of an earlier analysis that found no association between the drugs and cancer, said that finding might have been an aberration. “When you’re doing multiple analyses and splitting this way, that way and the other, the likelihood this is just a spurious finding is greater than the likelihood it’s real.”