Risk for early onset prostate cancer MAY BE increased in some infertile men


In posting the following commentary, we wish to be VERY clear that, at this time, there is no definitive evidence that there is a causal relationship between male infertility and risk for prostate cancer, but this does appear to be a POSSIBILITY. Furthermore, the paper reporting this possibility is probably going to get a lot of media attention, and so we would be remiss in not commenting on the new study.

Al-Jebari et al. have reported — in the British Medical Journal — a very thorough, retrospective analysis of data from 1.18 million men in Sweden who are know to have fathered at least one child between 1994 and 2014. The entire text of this paper is available on line, as is an editorial by Sharma and Jayasena. There is also a relevant media release available on the ScienceDaily web site.

What Al-Jebarai et al. have been able to show is that:

Men who achieved fatherhood through assisted reproduction techniques, particularly through [intra-cytoplasmic sperm injection], are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.

The ability to conduct this study is dependent on the high level of sophistication of the Swedish health database system. It is unlikely that such a study could be carried out in most countries around the world at this time.

The fundamental data from this study are as follow:

  • 1,181,490 children were born alive to the same number of fathers in Sweden over the 30 years between 1994 and 2014.
  • The fathers could be grouped according to their fertility status and by the mode of conception of the children:
    • 20,618 were conceived by in vitro fertilization (IVF).
    • 14,882 were conceived by intra-cytoplasmic sperm injection (ICSI)
    • 1,145,990 were conceived  by natural methods
  • It was also possible to tell which of the fathers went on to get a diagnosis of prostate cancer and when:
    • Among men achieving fatherhood by IVF, 77/20,618 (0.37 percent) were diagnosed with prostate cancer at an average (mean) age of 55.9 years.
    • Among men achieving fatherhood by ICSI, 63/14,882 (0.42 percent) were diagnosed with prostate cancer at an average age of 55.1 years.
    • Among men achieving fatherhood by natural, unassisted methods 3,244/1,145,990 (0.28 percent) were diagnosed with prostate cancer at an average age of 57.1 years.
  • Thus, compared to the men capable of conceiving children by natural means, men who conceived children via assisted reproduction methods were at greater risk for a diagnosis of prostate cancer:
    • For infertile men conceiving children via IVF, the hazard ratio (HR) was 1.33.
    • For infertile men conceiving children via ICSI, HR = 1.64.
  • Furthermore, again compared to the mnen capable of conceiving children by natural means, men who conceived children via assisted reproduction methods were at greater risk for a diagnosis of early prostate cancer (i.e., diagnosis at < 55 years of age):
    • For infertile men conceiving children via IVF, the hazard ratio (HR) was 1.51.
    • For infertile men conceiving children via ICSI, HR = 1.86.
  • Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy (ADT) to at least the same extent as the reference group (odds ratio = 1.91; P = 0.07).

Now there are all sorts of reasons why the data from this study need to be treated with great caution. Among the most important of the reasons are these:

  • The study inherently excluded infertile men who were unable to father children (and it is reasonable to think that such men might have a higher risk for prostate cancer than infertile men who managed to father children).
  • The average (mean) age of the men in this study at follow-up was only 45 years, so the findings don’t quantify risk of prostate cancer over the lifetimes of the men in this study.
  • Data on PSA testing in different population groups might have shown that infertile men were not subjected to enhanced cancer screening.

Given these study limitations, all we have here is an hypothesis: that men who achieve fatherhood through assisted reproduction techniques seem to be at increased risk for early onset prostate cancer. However, the study does imply that men who required assisted reproduction techniques to achieve fatherhood may be wise to consider themselves as being at increased risk for prostate cancer and discuss this with their physicians.

We also need to be clear that this study does not tell us whether the men in this study were at an level of increased risk for the more clinically significant forms of prostate cancer as opposed to the low- and very low-risk forms of prostate cancer.

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