Male Factor Infertility Linked to Risk for Testicular Cancer

Laurie Barclay, MD

March 03, 2009

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March 3, 2009 — Men with male factor infertility have an increased risk for the subsequent development of testicular cancer, according to the results of a study reported in the February 23 issue of the Archives of Internal Medicine.

"The risk of testicular cancer is thought to be higher among men seeking infertility treatment compared with the general population," write Thomas J. Walsh, MD, MS, from University of California–San Francisco and colleagues. "Confirmation of this risk in a large US cohort of at-risk patients is lacking. This study explored the association between male infertility and subsequent development of testicular cancer in a US-based cohort."

The study cohort consisted of 51,461 couples evaluated for infertility from 1967 to 1998 at 15 California infertility centers. Data from 22,562 identified male partners were linked to the California Cancer Registry. Using the Surveillance Epidemiology and End Results program, the investigators compared the incidence of testicular cancer in this cohort vs an age-matched, general-population sample. A Cox proportional hazards regression model allowed determination of the risk for testicular cancer in men with and without male factor infertility.

Male factor infertility was determined by the clinical presentation with abnormal semen analysis variables as defined by World Health Organization criteria.

There were 34 cases of histologically confirmed testicular cancer in men who had been previously diagnosed with infertility. The risk for the subsequent development of testicular cancer was increased in men seeking infertility treatment (standardized incidence ratio [SIR], 1.3; 95% confidence interval [CI], 0.9 - 1.9), with more than double the increased risk in men with known male factor infertility (SIR, 2.8; 95% CI, 1.5 - 4.8).

Multivariable analysis showed that men with male factor infertility were nearly 3 times more likely to have testicular cancer vs men without this condition (hazard ratio, 2.8; 95% CI, 1.3 - 6.0).

"Men with male factor infertility have an increased risk of subsequently developing testicular cancer, suggesting the existence of common etiologic factors for infertility and testicular cancer," the study authors write.

Limitations of this study include possible unmeasured confounding and lack of data concerning cryptorchidism, which is another potential cause of infertility and testicular cancer.

"The association between infertility and testicular cancer has been shown to be biologically and clinically feasible," the study authors write. "More importantly, the association between male infertility and testicular germ cell cancer should stimulate further research that focuses on the etiology of poor germ cell health in these populations."

The National Institute of Child Health and Human Development and the California Urology Foundation supported this study. The study authors have disclosed no relevant financial relationships.

Arch Intern Med. 2009;169:351-356.

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