The Daily Mail reports that “young, infertile men are ‘50% more likely to develop aggressive prostate cancer’”.
This news report is based on a study using the medical records of over 22,000 men in California who had been assessed for infertility. It found that men who were infertile were more likely to go on to develop prostate cancer, particularly more advanced prostate cancer, than men who were not infertile. This research does have some limitations, including its reliance on medical records and the fact that not many of the men developed the more aggressive type of prostate cancer, which weakens the reliability of the results.
Overall, these results will need to be confirmed in larger studies, preferably prospectivecohort studies. It is also important to bear in mind that the risk of developing prostate cancer, even among men who were infertile, was relatively low.
Where did the story come from?
Dr Thomas J. Walsh and colleagues from the University of Washington and other research centres in the US carried out this research. The study was funded by he National Institutes of Health as well as other charitable and governmental organisations. The research paper was published in the peer-reviewed medical journal Cancer.
The Daily Mail, BBC News and The Daily Telegraph covered this study. These sources provide generally accurate coverage of the research, although it is not clear exactly where the Mail’s headline figure of an increase of 50% in prostate cancer risk came from. All of the articles balance their report with a quote from Dr Helen Rippon, of the Prostate Cancer Charity. Dr Rippon commented that there is a difficulty in drawing firm conclusions from this study, considering that few of the men involved developed aggressive prostate cancer.
What kind of research was this?
This retrospective cohort study investigated whether there is a relationship between male infertility and the risk of prostate cancer. Some previous studies have suggested that men without children are at greater risk of prostate cancer than men with children, while other studies have not found such a link. The researchers in the current study wanted to look directly at infertility as a risk factor, as opposed to whether or not a man had children, which could be a matter of choice or other factors such as their partner’s fertility.
This study used data that is routinely recorded by infertility clinics and cancer registries in California. Preliminary studies such as this that test whether there is an association between two factors often use data that has already been collected, as it is cheaper and quicker than having to recruit people and then follow them up over time. The reliability of such studies depends on the accuracy and completeness of the recorded data. In cases where a link is found, researchers may go on to carry out a prospective cohort study, collecting their own data to confirm their findings.
What did the research involve?
The researchers looked at data on 22,562 men who attended infertility clinics in California between 1967 and 1998. The infertility status (whether the man was infertile or not) was known for 19,106 of these men. Male infertility, also known as “male factor infertility” was defined according to parameters set out by the World Health Organization. According to these parameters, 4,548 men were infertile and 14,557 were not. The infertility status of 3,456 men was unknown. The researchers then looked at the California Cancer Registry database to find any of these men who were diagnosed with prostate cancer between 1988 and 2004. They then compared the rate of prostate cancer between men with infertility and those without.
Men who were diagnosed with cancer either before their infertility evaluation or within a year of their evaluation were not included in the analysis. This avoided the possibility that either the cancer or cancer treatment caused the infertility. The main analyses compared men with and without male factor infertility. The analyses took into account the men’s ages, duration of infertility treatment, and where they were treated. They also looked at different severities of prostate cancer based on a standard rating system called the Gleason score. A Gleason score of seven or lower indicates low-grade (less severe/aggressive) prostate cancer, and a Gleason score of 8 to 10 indicates high-grade (more severe/aggressive) prostate cancer.
The researchers also compared the rate of prostate cancer in their overall study group, and in groups with and without infertility, against the overall rate of prostate cancer in California. These analyses took into account men’s ages.
What were the basic results?
Men with infertility were slightly older than men without infertility (average age of 38.1 compared with 36.4), and received infertility care for longer (for an average of 1.7 years compared with 1.5 years). Men were followed up for an average of 11.4 years after their infertility assessment. In this period, 168 of the 22,562 men were diagnosed with prostate cancer, a rate not significantly different from that in the general population.
There was a higher prostate cancer rate in infertile men (1.2%) than in men found not to be infertile (0.4%). Infertile men were about 1.8 times more likely to develop prostate cancer than men who were found not to be infertile after taking into account age, duration of infertility treatment, and where they were treated. The risk was particularly increased for higher-grade cancers, where men with infertility were at 2.6 times the risk of men without infertility.
Compared to the general population of Californian men, infertile men were slightly more likely to develop any prostate cancer, but this increase was only just statistically significant. However, infertile men were twice as likely as the general population to be diagnosed with high-grade prostate cancer, and this difference was statistically significant. Men without infertility were slightly less likely than the general population to develop prostate cancer.
How did the researchers interpret the results?
The researchers conclude that the infertile men had a higher risk of developing high-grade prostate cancer. They say, “Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.”
This large registry-based study has suggested that infertile men may be at increased risk of high-grade prostate cancer. There are a number of points to note:
- This study relied on data recorded as part of routine practice. Some data may have been misrecorded, and some information may be missing. For example, men who moved out of California and were diagnosed with cancer would not have been identified. This may affect the reliability of the results.
- As the authors themselves note, some other studies have found no link between fertility and risk of prostate cancer. This may be because these studies relied on lack of offspring to indicate infertility, and all men without children are not necessarily infertile.
- As with all observational studies, it is possible that other factors are contributing to the differences between the groups. This study took into account some factors that could be having an effect, but there may be other unknown or unmeasured factors that were not accounted for. This may particularly be the case in comparisons between infertile men and the general population – who are more likely to have differing characteristics – than in comparisons between infertile men and those screened for infertility but found not to be infertile.
- In particular, the authors suggest that men with infertility may be more likely to undergo screening for prostate cancer as part of their medical assessments than men without infertility, and this would increase the chances of any prostate cancers being found in the infertile group. However, the fact that the risk of low-grade cancers was not significantly increased in infertile men suggests that this may not be the case.
- As prostate cancer is relatively uncommon, the analyses could only include a relatively small number of men with prostate cancer: 168 in total. The number of men with high-grade tumours was therefore even smaller: 45. Analyses looking at such small numbers of individuals may be more susceptible to being affected by chance, so the results for high-grade tumours should be interpreted cautiously.
- This study is not able to tell us whether different types of male infertility are associated with greater or lower risk of prostate cancer, or whether it is the condition, the treatment, or some other related factor that is associated with the increase in risk. The authors suggest that it seems unlikely that treatments are to blame, as in most cases men will not receive treatment for their infertility. Instead, they and their partner will receive assisted reproduction techniques such as IVF.
Overall, these results will need confirmation in other studies, preferably prospective cohort studies if possible. It is also important to note that the risk of developing prostate cancer, even among men who were infertile, was relatively low.
Links to the headlines
Young infertile men are ‘50% more likely to develop aggressive prostate cancer’. Daily Mail, March 22 2010
Infertility clue to prostate cancer. BBC News, March 22 2010
Infertile men have increased risk of aggressive prostate cancer. The Daily Telegraph, March 22 2010
Links to the science
Walsh TJ, Schembri M, Turek PJ, et al. Increased risk of high-grade prostate cancer among infertile men (p NA). Cancer 2010; published online: March 22 2010