Increased risk of cancer among azoospermic men

Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development.

Michael L. Eisenberg, M.D., Paul Betts, M.S., Danielle Herder, M.D., Dolores J. Lamb, Ph.D., Larry I. Lipshultz, M.D.

Volume 100, Issue 3, Pages 681-685.e1, September 2013


To determine whether men with azoospermia are at an elevated risk of developing cancer in the years following an infertility evaluation.

Cohort study.

United States andrology clinic.

A total of 2,238 men with complete records were evaluated for infertility at a single andrology clinic in Texas from 1989 to 2009.


Main Outcome Measure(s):
Cancer incidence was determined by linkage to the Texas Cancer Registry.

In all, 451 men had azoospermia, and 1,787 were not azoospermic, with a mean age at infertility evaluation of 35.7 years. Compared with the general population, infertile men had a higher risk of cancer, with 29 cases observed compared with 16.7 expected (standardized incidence rate [SIR] 1.7, 95% confidence interval [CI] 1.2–2.5). When stratifying by azoospermia status, azoospermic men had an elevated risk of cancer (SIR 2.9, 95% CI 1.4–5.4). Infertile men without azoospermia had a trend toward a higher rate of cancer (SIR 1.4, 95% CI 0.9–2.2). The Cox regression model revealed that azoospermic men had 2.2-fold higher cancer risk compared with nonazoospermic men (hazard ratio 2.2, 95% CI 1.0–4.8).

Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development. Additional follow-up of azoospermic men after reproductive efforts end may be warranted.

  • Carlos Balmori

    Congratulations for the article.
    It would be interesting to study whether a immunohistochemical or histopathological pattern is repeated in testicular tissues from
    patients with azoospermia and NOA. Also the correlation with certain biomarkers
    can help you find the correlation between cancer and infertility.

    • Michael Eisenberg

      Exploring the underlying mechanism of the association between azoospermia and cancer will be key.

  • Amanda N. Kallen

    Very interesting study on a topic that certainly merits our attention. The research raised two questions for me:

    First question – regarding the azoospermia vs non-azoospermia categories – when the authors stratified out the “likely nonobstructive” cases based on chart review, was there any increase in cancer risk in the obstructive azoospermia cohort? I would expect the answer to be “no” given the pathogenesis of that particular diagnosis.

    And the second question – there were more cases of prostate cancer in the non-azoospermia cohort. Was this a significant difference, and did the authors have any speculation as to why this might be so?

    Again, very interesting article and I agree with Dr. Hsieh that it would be interesting also to look at outcomes in light of fertility status.

    • Michael Eisenberg

      Two great questions. Unfortunately the limited numbers in our cohort prevented looking only at men with available chart review. For similar reasons, we couldn’t look at individual malignancies. However, there were men without azoospermia compared to those with azoospermia which may explain the higher number of prostate cancers.

  • Very timely article by Dr. Eisenberg. As Urologists, we have been focused on the increased risk of GU malignancies in infertile men as a group.

    The results of this article have brought up 2 very important issues previously not addressed in other studies:
    1. Azoospermic men have a 2.9 fold higher cancer risk over the general public compared to just infertile men as a whole.
    2. Infertile men have a higher risk of not only GU focused malignancies.

    These findings provide additional evidence for continued close health monitoring of these patients after fertility is achieved not only by their urologists but also by their primary health providers.

    • Jason Kovac

      Agree. Indeed, work in Dr. Lamb’s laboratory is currently being performed to elucidate the molecular mechanisms involved in why certain cell types in men with azoospermia are more prone to the development of malignancies…. stay tuned !

  • Michael Eisenberg

    Dr. Hsieh raises an interesting question. In 2010, our group looked at the association between fatherhood status and prostate cancer incidence and mortality. Interesting, there was a trend toward a lower risk of prostate cancer death in fathers compared to childless men. Reproductive potential and intent in these men was not known but it does suggest impaired outcomes in these men. However, simply not having children can increase risk for adverse outcomes so any future studies must account for this.

  • Another article showing the association between male infertility and cancer. It would be interesting to see if cancer treatment outcomes are effected by fertility status.

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