Women with a history of fertility complications may face a higher risk of developing certain cancers, suggests a new government study, though the likelihood of cancer was lower in some patients in the study.¹

This isn't the first time infertility has been linked with cancer, explained Louise Brinton, PhD, in the division of Cancer Epidemiology and Genetics at the National Cancer Institute, who headed the research. But the study expands on current knowledge by linking certain causes of infertility with certain types of cancer, she said.

"A strength of our research was in having extensive information to classify different causes of infertility, e.g., endometriosis, anovulation [no ovulation], tubal factor, uterine or cervical abnormalities [and] male factor problems," Brinton told Priority Healthcare.

Other studies have suggested there's an increased risk of endometrial and breast cancers associated with varying types of infertility. "A few studies have suggested relationships with thyroid cancer and melanoma," she added.5 But few studies have looked extensively at the underlying causes for this increased cancer risk.

Infertility Cancer Connection Studied
Brinton and her colleagues conducted a look-back analysis of more than 12,000 U.S. women who had been diagnosed with infertility between the years 1965 and 1988. Their risk of developing certain cancers was compared with that of the general population.

The research team identified nearly 600 cases of cancer through 1999 in the group of women they studied.

After taking other potential factors into account that would otherwise boost the risk of cancer in the group, Brinton and her fellow investigators found the women faced, on average, a 23% higher risk of developing cancer compared to those in the general population.

Other Risk Factors
Women with primary infertility had even a higher risk—up to one-and-a-half times the odds compared to the general population—than those with infertility caused by another condition, such as endometriosis or polycystic ovary syndrome (PCOS).

"Particularly elevated risks among primary infertility patients were observed for cancers of the uterus and ovaries," the study team noted. The risk associated with uterine cancers was nearly twice that of the general population, and more than two-and-a-half times greater for ovarian cancer.

Those with a diagnosis of endometriosis had greater rates of colon, ovarian, and thyroid cancers, as well as melanomas. In endometriosis patients, the average risk of colon cancer was about 2.4 times greater (though some patients had a lower risk); there was a nearly three-fold greater risk of ovarian cancer, on average; and the average thyroid cancer risk was more than four-and-a-half times higher (though, again, some patients in this group faced a lower risk than the general population).

"Melanomas were linked with anovulatory problems, whereas uterine cancers predominated among patients with tubal disorders," Brinton's group wrote.

Women with primary infertility due to anovulation were "particularly predisposed" to developing uterine cancer. Those with tubal disorders as the cause of their primary infertility were more apt to develop ovarian cancer, they found. The average risk of uterine cancer in the anovulatory group was about 2.4 times higher, and the risk, on average, of ovarian cancer in the group with tubal disorders was about 1.6 times greater, although some patients faced the same risk as the general population in both these categories.

Infertility due to a male problem is also associated with the increased cancer risk, the study team found. "Primary infertility associated with male-factor problems was associated with unexpected increases in colon [nearly three times greater risk] and uterine cancers [more than triple the risk]," they wrote.

Underlying Causes Behind Cancer
Why are these specific infertility causes linked with a heightened risk of cancer? "Anovulation has generally been linked to underlying hormonal problems," Brinton explained. "Tubal factor has generally been related to infectious agents. Endometriosis is a complex condition which might relate to either hormonal or immunologic factors."

As a result of their findings, it's apparent that the infertility in women may have an impact on the development of various types of cancers, not just those that are gynecologic in nature, the researchers noted. Additionally, "thyroid cancers and melanomas deserve specific attention, particularly with respect to endometriosis," Brinton and her colleagues concluded.

Similar Findings
In a review paper on the topic,² a team of Australian researchers observed that infertile women may face a higher risk of uterine cancer, particularly those diagnosed with certain ovulation disorders. However, "most studies show no increase in the risk of invasive ovarian cancer in infertile women, but ovarian tumors of borderline malignancy are more common."

Men diagnosed with infertility appear to face an increased risk of testis cancer, they added.

In a more recent retrospective study,³ Brinton and her colleagues noted that ovarian cancer risk was significantly higher for women diagnosed with infertility. On average, they faced nearly two times the risk compared to women in the general population. Similar to the findings of their most recent analysis, the researchers concluded that women with primary infertility faced the highest risk compared to those with infertility due to another cause. "It was particularly high [nearly three-and-a-half times the risk] for women who never subsequently conceived," they wrote.

Women with endometriosis had about 2-and-a-half times the risk of the general population, on average, in this study, though some patients faced only a slightly increased risk.

"Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes," the NIH investigators concluded. "Further study of endometriosis may provide insights into ovarian [cancer origins]."

Practical Implications
How can patients determine whether they're at risk for these cancers or not? While a test isn't yet available that allows physicians to predict which of their infertility patients might face an increased cancer risk based on a biological "marker", or indicator, Brinton says she and her team are exploring some options. She says her team hopes to pursue some of these issues, "particularly with respect to defining biomarkers that might predict the development of ovarian cancer among women with endometriosis."

1. Brinton LA, Westhoff CL, Scoccia B et al. Causes of infertility as predictors of subsequent cancer risk. Epidemiology 2005 Jul;16(4):500-7.
2. Venn A, Healy D, McLachlan R. Cancer risks associated with the diagnosis of infertility. Best Pract Res Clin Obstet Gynaecol 2003 Apr;17(2):343-67.
3. Brinton LA, Lamb EJ, Moghissi KS et al. Ovarian cancer risk associated with varying causes of infertility. Fertil Steril 2004 Aug;82(2):405-14.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.