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Original Research

Open Access

Male Infertility and Subsequent Risk of Cancer Development

  • Michael Lao1
  • Stanton C. Honig2

1resident at The University of Connecticut Health Center, Division of Urology, Farmington, CT

2Director of Men’s Health in the Department of Urology, Yale School of Medicine, in New Haven CT

DOI: 10.31083/jomh.v11i6.17 Vol.11,Issue 6,December 2015 pp.19-28

Published: 07 December 2015

*Corresponding Author(s): Michael Lao E-mail:
*Corresponding Author(s): Stanton C. Honig E-mail:

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Infertility occurs in 15% of the population; and 30–50% of the time, the problem is due to a male factor. There is active research attempting to elucidate how male factor infertility fits into the picture of overall men’s health. Research in the past has established that a thorough male fertility evaluation can uncover various medical pathologies. There is now growing evidence that suggests male infertility is a potential harbinger for subsequent cancer development. In this review of pertinent articles, the current evidence regarding fertility and development of genitourinary and other cancers will be discussed, in particular, testicular and prostate cancer. In addition, various etiologic factors that explain the pathophysiology of infertility and progression to cancer will also be reviewed. It is possible that male factor infertility is a surrogate marker for subsequent cancer development. 


infertility, cancer, prostate, testes, oncology

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Michael Lao,Stanton C. Honig. Male Infertility and Subsequent Risk of Cancer Development. Journal of Men's Health. 2015. 11(6);19-28.


1. MacLeod, J.: Human male infertility. Obstet Gynecol Surv, 26: 335, 1971

2. Simmons, F. A.: Human infertility. N Engl J Med, 255: 1140, 1956

3. Honig, S. C., Lipshultz, L. I., Jarow, J.: Significant medical pathology uncovered by a comprehensive male infertility evaluation. Fertil Steril, 62: 1028, 1994

4. Kolettis, P. N., Sabanegh, E. S.: Significant medical pathology discovered during a male infertility evaluation. J Urol, 166: 178, 2001

5. Sigman, M., Jarow, J. P.: Endocrine evaluation of infertile men. Urology, 50: 659, 1997

6. Walsh, T. J., Croughan, M. S., Schembri, M. et al..: Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med, 169: 351, 2009

7. Jacobsen, R., Moller, H., Thoresen, S. O. et al..: Trends in testicular cancer incidence in the Nordic countries, focusing on the recent decrease in Denmark. Int J Androl, 29: 199, 2006

8. Huyghe, E., Matsuda, T., Thonneau, P.: Increasing incidence of testicular cancer worldwide: a review. J Urol, 170: 5, 2003

9. Doria-Rose, V. P., Biggs, M. L., Weiss, N. S.: Subfertility and the risk of testicular germ cell tumors (United States). Cancer Causes Control, 16: 651, 2005

10.  Raman, J. D., Nobert, C. F., Goldstein, M.: Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol, 174: 1819, 2005

11. Jacobsen, R., Bostofte, E., Engholm, G. et al..: Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ, 321: 789, 2000

12. Moller, H., Skakkebaek, N. E.: Risk of testicular cancer in subfertile men: case-control study. BMJ, 318: 559, 1999

13.  Moller, H.: Trends in sex-ratio, testicular cancer and male reproductive hazards: are they connected? APMIS, 106: 232, 1998

14.  Jacobsen, R., Bostofte, E., Engholm, G. et al..: Fertility and offspring sex ratio of men who develop testicular cancer: a record linkage study. Hum Reprod, 15: 1958, 2000

15.  Moller, H., Skakkebaek, N. E.: Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark. Cancer Causes Control, 8: 904, 1997

16.  Aetiology of testicular cancer: association with congenital abnormalities, age at puberty, infertility, and exercise. United Kingdom Testicular Cancer Study Group. BMJ, 308: 1393, 1994

17.  Pukkala, E., Weiderpass, E.: Socio-economic differences in incidence rates of cancers of the male genital organs in Finland, 1971-95. Int J Cancer, 102: 643, 2002

18. Nudell, D., Castillo, M., Turek, P. J. et al..: Increased frequency of mutations in DNA from infertile men with meiotic arrest. Hum Reprod, 15: 1289, 2000

19.  Baker, S. M., Plug, A. W., Prolla, T. A. et al..: Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet, 13: 336, 1996

20.  de Wind, N., Dekker, M., Berns, A. et al..: Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell, 82: 321, 1995

21.  Skakkebaek, N. E., Rajpert-De Meyts, E., Main, K. M.: Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod, 16: 972, 2001

22.  Walsh, T. J., Schembri, M., Turek, P. J. et al..: Increased risk of high-grade prostate cancer among infertile men. Cancer, 116: 2140, 2010

23. Gronberg, H.: Prostate cancer epidemiology. Lancet, 361: 859, 2003

24.  Jorgensen, K. T., Pedersen, B. V., Johansen, C. et al..: Fatherhood status and prostate cancer risk. Cancer, 112: 919, 2008

25.  Giwercman, A., Richiardi, L., Kaijser, M. et al..: Reduced risk of prostate cancer in men who are childless as compared to those who have fathered a child: a population based case-control study. Int J Cancer, 115: 994, 2005

26.  Negri, E., Talamini, R., Bosetti, C. et al..: Risk of prostate cancer in men who are childless. Int J Cancer, 118: 786, 2006

27. Dennis, L. K., Dawson, D. V.: Meta-analysis of measures of sexual activity and prostate cancer. Epidemiology, 13: 72, 2002

28.  Roetzheim, R. G., Pal, N., Tennant, C. et al..: Effects of health insurance and race on early detection of cancer. J Natl Cancer Inst, 91: 1409, 1999

29.  Harlap, S., Paltiel, O., Friedlander, Y. et al..: Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort. J Natl Cancer Inst, 99: 77, 2007

30.  Hirata, H., Hinoda, Y., Kawamoto, K. et al..: Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer. J Urol, 179: 2020, 2008

31.  Swerdlow, A. J., Schoemaker, M. J., Higgins, C. D. et al..: Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst, 97: 1204, 2005

32. Wang, C., Baker, H. W., Burger, H. G. et al.: Hormonal studies in Klinefelter’s syndrome. Clin Endocrinol (Oxf), 4: 399, 1975

33.  Hasle, H., Mellemgaard, A., Nielsen, J. et al..: Cancer incidence in men with Klinefelter syndrome. Br J Cancer, 71: 416, 1995

34.  Swerdlow, A. J., Hermon, C., Jacobs, P. A. et al..: Mortality and cancer incidence in persons with numerical sex chromosome abnormalities: a cohort study. Ann Hum Genet, 65: 177, 2001

35. Hultborn, R., Hanson, C., Kopf, I. et al..: Prevalence of Klinefelter’s syndrome in male breast cancer patients. Anticancer Res, 17: 4293, 1997

36.  Eisenberg, M. L., Betts, P., Herder, D. et al..: Increased risk of cancer among azoospermic men. Fertil Steril, 100: 681, 2013

37.  Walsh, T. J.: Male reproductive health and prostate cancer risk. Curr Opin Urol, 21: 506, 2011

38.  Perinchery, G., Sasaki, M., Angan, A. et al..: Deletion of Y-chromosome specific genes in human prostate cancer. J Urol, 163: 1339, 2000

39. Stahl, P.J., Masson, P., Mielnik, A. et al.: A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligospermia. Fertil Steril, 94: 1753, 2010

40.  Nathanson, K. L., Kanetsky, P. A., Hawes, R. et al..: The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am J Hum Genet, 77: 1034, 2005

41.  Bianchi, N. O., Richard, S. M., Pavicic, W.: Y chromosome instability in testicular cancer. Mutat Res, 612: 172, 2006

42.  Vogt, P. H., Edelmann, A., Kirsch, S. et al..: Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet, 5: 933, 1996

43. Reijo, R., Alagappan, R. K., Patrizio, P. et al..: Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet, 347: 1290, 1996

44.  Kostiner, D. R., Turek, P. J., Reijo, R. A.: Male infertility: analysis of the markers and genes on the human Y chromosome. Hum Reprod, 13: 3032, 1998

45. Kleiman, S. E., Bar-Shira Maymon, B., Yogev, L. et al..: The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells. Hum Reprod, 16: 399, 2001

46. Bermejo, J. L., Sundquist, J., Hemminki, K.: Re: Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort. J Natl Cancer Inst, 99: 901, 2007

47.  James, W. H.: Re: Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort. J Natl Cancer Inst, 99: 902; author reply 903, 2007

48.  Olesen, I. A., Sonne, S. B., Hoei-Hansen, C. E. et al..: Environment, testicular dysgenesis and carcinoma in situ testis. Best Pract Res Clin Endocrinol Metab, 21: 462, 2007

49. Spierings, D. C., de Vries, E. G., Vellenga, E. et al..: The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis-inducing stimuli. J Pathol, 200: 137, 2003

50.  Mosaad, Y. M., Shahin, D., Elkholy, A. A. et al..: CAG repeat length in androgen receptor gene and male infertility in Egyptian patients. Andrologia, 44: 26, 2012

51.  Rodriguez-Gonzalez, G., Cabrera, S., Ramirez-Moreno, R. et al..: Short alleles of both GGN and CAG repeats at the exon-1 of the androgen receptor gene are associated to increased PSA staining and a higher Gleason score in human prostatic cancer. J Steroid Biochem Mol Biol, 113: 85, 2009

52.  Silva Neto, B., Koff, W. J., Biolchi, V. et al..: Polymorphic CAG and GGC repeat lengths in the androgen receptor gene and prostate cancer risk: analysis of a Brazilian population. Cancer Invest, 26: 74, 2008

53.  Das, K., Cheah, P. Y., Lim, P. L. et al..: Shorter CAG repeats in androgen receptor and non-GG genotypes in prostate-specific antigen loci are associated with decreased risk of benign prostatic hyperplasia and prostate cancer. Cancer Lett, 268: 340, 2008

54.  Rajender, S., Avery, K., Agarwal, A.: Epigenetics, spermatogenesis and male infertility. Mutat Res, 727: 62, 2011

55.  Jeronimo, C., Bastian, P. J., Bjartell, A. et al..: Epigenetics in prostate cancer: biologic and clinical relevance. Eur Urol, 60: 753, 2011

56.  Skinner, M. K., Guerrero-Bosagna, C.: Environmental signals and transgenerational epigenetics. Epigenomics, 1: 111, 2009 

57. Phillips, K. P., Tanphaichitr, N.: Human exposure to endocrine disrupters and semen quality. J Toxicol Environ Health B Crit Rev, 11: 188, 2008

58.  Prins, G. S.: Endocrine disruptors and prostate cancer risk. Endocr Relat Cancer, 15: 649, 2008

59.  Xu, X., Dailey, A. B., Talbott, E. O. et al..: Associations of serum concentrations of organochlorine pesticides with breast cancer and prostate cancer in U.S. adults. Environ Health Perspect, 118: 60, 2010

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