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Fertility drugs and ovarian cancer

No increased risk


Source: British Medical Journal, March 7; 2009

The largest study on the subject of association between fertility drugs and ovarian cancer to date has concluded that  these drugs do not increase the risk for ovarian cancer.

No convincing association with ovarian cancer for any of the 4 different types of drugs used to treat infertile women — (gonadotrophins, clomiphene citrate, human chorionic gonadotrophin, and gonadotrophin-releasing hormone) was found.

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.

The only significant limitation for the study was the age of the participants.  Many of them have not yet reached the age at which the incidence of ovarian cancer peaks (early 60s).

The study was headed by Allen Jensen, PhD, assistant professor of cancer epidemiology at the Danish Cancer Society's Institute of Cancer Epidemiology, in Copenhagen, Denmark. It was funded by the Danish Cancer Society.

Given the increasing numbers of women seeking fertility treatment, many experts agree that this is important information for clinicians and patients as well as additional reassurance.

History of link between fertility drugs and ovarian cancer

A link between fertility drugs and increased risk for ovarian cancer was suggested by several studies in the early 1990s. This has inevitably caused a lot of worry for patients undergoing fertility treatment. However, many of the studies over the past 8 to 10 years have been very small and have not moved the evidence one way or the other.

Clomid and ovarian cancer

Infertility has previously been associated with an increased risk for ovarian cancer. In an epidemiological study of 3837 women treated for infertility, Rossing and colleagues demonstrated that infertility increased the risk for malignant ovarian tumours by a factor of 2.5 compared to the overall community prevalence of ovarian cancer. This study, which was published in the September 22, 1994, issue of the New England Journal of Medicine, also suggested that the use of Clomiphene (Clomid) in particular could increase the risk for ovarian cancer, particularly in women who had used the medication for more than 12 months.


This study was big enough to enable reliable conclusions to be arrived at. Significantly, the study included 156 women with ovarian cancer, more than 3 times as many as any previous cohort."

The issue of age

The main limitation of the study, however, is the age of the participants. The women were relatively young. 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. The follow-up was quite long, lasting many years and the study group was quite large involving thousands of women. The findings are therefore quite reassuring. The longer term situation, when these women reach their late 50s and 60s is the question that cannot be answered yet. The researchers intend to re-visit the data at regular points in the future to check on the progress of the study cohort with passive surveillance.


Small possibility not excluded

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 absolutely exclude the possibility of a small increase in the risk for ovarian cancer in users of fertility drugs.



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.

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.



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