FERTILITY DRUGS AND OVARIAN CANCER

Fertility Drugs Do Not Increase Risk for Ovarian Cancer

February 5, 2009 — Fertility drugs do not increase the risk for ovarian cancer, concludes the largest study of the subject to date.

There was no convincing association with ovarian cancer for any the 4 different types of drugs used to treat infertile women — gonadotrophins, clomiophene citrate, human chorionic gonadotrophin, and gonadotrophin-releasing hormone.

Instead, the data suggest that factors related to the diagnosis of infertility (for example, genetic or biological factors) — and not the use of fertility drugs — increase the overall risk for ovarian cancer, say the researchers.

However, they also point out that there is a major limitation to this study — many of the participants have not yet reached the age at which the incidence of ovarian cancer peaks (early 60s).

The study, headed by Allen Jensen, PhD, assistant professor of cancer epidemiology at the Danish Cancer Society's Institute of Cancer Epidemiology, in Copenhagen, Denmark, is reported online February 5 in BMJ.

"These data are reassuring and provide further evidence that fertility drugs do not increase a woman's risk of ovarian cancer to any great extent, although small increases in risk cannot be ruled out," said Penelope Webb, from the Queensland Institute of Medical Research, in Brisbane, Australia, in an accompanying editorial.

"Given the increasing numbers of women seeking fertility treatment, this is important information for clinicians and patients," she adds.

Main Limitation is Age of Participants

"The data are reassuring," agrees senior author Susanne Kruger Kjaer, MD, professor of cancer epidemiology at the Danish Cancer Society and the Juliane Marie Center at Copenhagen University Hospital.

A link between fertility drugs and increased risk for ovarian cancer was suggested by several studies in the early 1990s, and this has caused a lot of worry for patients undergoing infertility treatment, she commented an interview with Medscape Oncology. However, many of the studies over the past 8 to 10 years have been very small, and "none were really able to reject or confirm the hypothesis and the worries," she continued.

"Our study was big enough," she added.

Dr. Webb concurs, and writes: "This study is important because it included 156 women with ovarian cancer, more than 3 times as many as any previous cohort."

However, Dr. Kjaer noted 2 caveats. One is that the study was restricted to epithelial ovarian cancer; 6 cases of ovarian cancer of unknown histology and 11 cases of ovarian cancer that was nonepithelialere excluded because these cancers may have different behaviors, she explained.

The main limitation of the study, however, is the age of the participants. These were young women, Dr. Kjaer explained — they were first evaluated for infertility at a median age of 30 years. Despite a long follow-up, the median age of these women at the end of the follow-up period was 47 years. This is some way below the usual age at which women are diagnosed with ovarian cancer, which reaches a peak incidence in women in their early 60s. So there is a possibility that there could still be a spate of ovarian cancers diagnosed as these women age, which could alter the conclusions.

"This is my only 'but' in the results, so to speak," Dr. Kjaer told Medscape Oncology.

"This is a question that nobody can answer yet," she added. Hence, she continued, " we should say that the data so far are really reassuring . . . at this moment, with this observation period, and with this age of the cohort, we cannot see any association with an increase in the risk of ovarian cancer."

The researchers intend to revisit the data at regular points in the future to check on the progress of the study cohort with "passive surveillance," she said. The Danish system of personal identification numbers and nationwide health and cancer registries will allow them to track any new diagnosis of ovarian cancer, she added.

Cannot Exclude Small Possibility

The Danish study investigated the records of 54,362 women with infertility problems, and compared 156 women who developed invasive epithelial ovarian cancer with 1241 controls.

However, although this study was much larger than previous investigations, it still could not exclude the possibility of a small increase in the risk for ovarian cancer in users of fertility drugs, Dr. Webb writes in the editorial. The rate ratio for use of any fertility drug was 1.03, but the upper bound of the 95% confidence interval was 1.47, she points out.

"Larger numbers of women will need to be studied to answer this question, and these will come with further follow-up of the cohort as they enter the age range where ovarian cancer is most common," Dr. Webb comments. "Some women who take fertility drugs will inevitably develop ovarian cancer by chance alone, but current evidence suggests that women who use these drugs do not have an increased risk."