Male Infertility Increases Overall Cancer Risk

Nick Mulcahy

June 21, 2013

Infertile men — especially those without any sperm in their ejaculate — are at increased risk of developing cancer, compared with the general population, according to a new study.

The study is the first to report an increased risk for cancer in men with an absence of sperm, or azoospermia, note the authors, led by Michael Eisenberg, MD, PhD, director of male reproductive medicine and surgery at Stanford Hospital & Clinics in Palo Alto, California.

The results were published online June 24 in Fertility and Sterility.

The study is also important because it found that the infertile men — those without any sperm and those with ineffective sperm — developed a variety of malignancies, including prostate cancer, brain and central nervous system (CNS) cancer, melanoma, and stomach cancer, as well as testicular cancer. Previous studies have found only a consistent association between infertility and testicular cancer, the authors write.

Dr. Eisenberg and coauthors evaluated 2238 men from a Texas infertility clinic — 451 with and 1787 without azoospermia. They compared the incidence of cancer in this cohort with that in the general population of Texas.

The median age at the initial infertility evaluation was 35.7 years. Median follow-up was 6.7 years.

Overall, 29 of the infertile men developed some type of cancer — 10 (2.2%) with azoospermia and 19 (1.1%) without azoospermia.

Compared with the general Texas population, the infertile men had a higher risk for overall cancer (standardized incidence ratio [SIR], 1.7; 95% confidence interval [CI], 1.2 - 2.5).

The risk for cancer was significantly higher in the azoospermic men than in the nonazoospermic men (SIR, 2.9; 95% CI, 1.4 - 5.4). "An azoospermic man's risk for developing cancer is similar to that for a typical man 10 years older," said Dr. Eisenberg in a press statement.

The rate of cancer in infertile men without azoospermia was similar to that in the general Texas population (SIR, 1.4; 95% CI, 0.9 - 2.2), but there was a trend toward an elevated risk, the authors report.

Should infertile young men seek cancer screening? Not necessarily, said Dr. Eisenberg.

"This study suggests that this group of men is at higher risk, but it's unclear if more intense screening would be helpful," he told Medscape Medical News in an email. "It's important to note that most reproductive-aged men (20s to 40s) don't have primary care doctors or really ever see the doctor. A lot of times, seeing a physician about fertility may be the first time they seek healthcare."

So the silver lining in this clinical cloud is that infertility might be an opportunity to connect men to the healthcare system and thus improve overall health, he said.

Genetics and Sperm Problems, Cancer

Dr. Eisenberg and his coauthors point out that they excluded any men who had a cancer diagnosis within 3 years of their infertility evaluation to rule out the possibility that the infertility was caused by an undiagnosed cancer.

Although the relative risk for cancer is elevated in men with azoospermia, the authors emphasize that "it is reassuring that the absolute risk [for cancer in infertile men] remains low."

Age at azoospermia diagnosis also influences the risk for cancer. Men who had a semen analysis prior to age 30 had the highest risk (SIR, 8.1; 95% CI, 1.0 - 29.3). In contrast, for the infertile men without azoospermia, there was no effect of age at semen analysis on cancer risk.

The authors place their findings in the context of the greater population. About 4 million American men — 15% of those 15 to 45 years of age — are infertile, they report. Of these, some 600,000 — about 1% of those of reproductive age — are azoospermic. This study suggests that most of the increased cancer risk in infertile men is in those with azoospermia.

Azoospermia is caused by an anatomically related blockage or a testicular deficiency in sperm production, which is perhaps genetically based, the authors explain. The great majority of men in the study had the latter problem, known as nonobstructive azoospermia. Azoospermia and cancer vulnerability can share common genetic causes, they note.

The study was funded by the National Institute for Child Health and Human Development.

Fertil Steril. Published online June 24, 2013. Abstract

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