title: Male reproductive cancers and infertility: a mutual relationship.
abstract: Reproductive dysfunction and malignancies related to the male gender represent a serious health concern, whose incidence has significantly risen over the past years. Prior to treatment, testicular or prostate cancer patients often display poor semen characteristics similar to subfertile or infertile patients. This fact is underscored by cases where the malignancy is often diagnosed in males who undergo a general fertility screening. This review aims to examine the associations between male infertility and reproductive cancers focusing on common etiologies and biological mechanisms underlining these pathologies. Furthermore, we discuss compelling epidemiological data hypothesizing that male reproductive failure may act as a precursor of future andrological malignancies, including testicular or prostate cancer, thus providing a stimulus for a more specific research in male reproductive health and emphasizing the importance of this relation for physicians taking care of male patients with a reproductive disease.
authors.affiliation: Center for Reproductive Medicine, Cleveland Clinic, Mail Code X-11, 10681 Carnegie Avenue, Cleveland, OH 44195, USA. evina.tvrda@gmail.com.|Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture, Tr. A. Hlinku 2, 94976 Nitra, Slovakia. evina.tvrda@gmail.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Tvrda
authors.affiliation: Center for Reproductive Medicine, Cleveland Clinic, Mail Code X-11, 10681 Carnegie Avenue, Cleveland, OH 44195, USA. agarwaa@ccf.org.
authors.forename: Ashok
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Center for Reproductive Medicine, Cleveland Clinic, Mail Code X-11, 10681 Carnegie Avenue, Cleveland, OH 44195, USA. nawafalkuhaimi@gmail.com.|College of Medicine, Alfaisal University, P.O. Box 50927, 11533 Riyadh, Saudi Arabia. nawafalkuhaimi@gmail.com.
authors.forename: Nawaf
authors.initials: N
authors.lastname: Alkuhaimi
mesh_terms: D000818:Animals; D005834:Genital Neoplasms, Male / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007248:Infertility, Male / Q000209:etiology* / Q000473:pathology*; D008297:Male; D060728:Reproductive Health
references.citation: Fertil Steril. 1994 Nov;62(5):1028-34
references.pmid: 7926114
references.citation: Cancer Control. 2010 Oct;17(4):245-55
references.pmid: 20861812
references.citation: J Urol. 1987 Mar;137(3):420-3
references.pmid: 3029434
references.citation: Environ Int. 2014 Sep;70:106-12
references.pmid: 24927498
references.citation: Pediatr Endocrinol Rev. 2009 Jun;6(4):476-80
references.pmid: 19550382
references.citation: Basic Clin Pharmacol Toxicol. 2008 Feb;102(2):155-61
references.pmid: 18226069
references.citation: Mol Carcinog. 2000 Apr;27(4):308-21
references.pmid: 10747295
references.citation: PLoS One. 2013 Oct 14;8(10):e77130
references.pmid: 24155923
references.citation: Hum Reprod. 1995 Aug;10(8):2017-22
references.pmid: 8567834
references.citation: Curr Opin Urol. 2011 Nov;21(6):506-13
references.pmid: 21941182
references.citation: J Behav Med. 2016 Feb;39(1):151-60
references.pmid: 20411318
references.citation: Prostate. 2007 Feb 1;67(2):214-25
references.pmid: 17044039
references.citation: J Hum Genet. 2002;47(6):279-84
references.pmid: 12111377
references.citation: Endocr Relat Cancer. 2005 Sep;12(3):631-43
references.pmid: 16172196
references.citation: Cell. 2006 Mar 24;124(6):1169-81
references.pmid: 16564011
references.citation: J Toxicol Environ Health B Crit Rev. 2009 Mar;12(3):206-23
references.pmid: 19466673
references.citation: Curr Opin Clin Nutr Metab Care. 2004 Jul;7(4):427-34
references.pmid: 15192446
references.citation: Hum Reprod Update. 2006 May-Jun;12(3):303-23
references.pmid: 16540528
references.citation: Urology. 2003 Nov;62(5):941
references.pmid: 14624928
references.citation: J Steroid Biochem Mol Biol. 2011 Oct;127(1-2):96-101
references.pmid: 21168493
references.citation: AAPS J. 2009 Dec;11(4):747-57
references.pmid: 19876744
references.citation: Oncogene. 2003 Mar 27;22(12):1880-91
references.pmid: 12660824
references.citation: J Clin Oncol. 1997 Apr;15(4):1444-8
references.pmid: 9193338
references.citation: Clin Oncol (R Coll Radiol). 2007 Mar;19(2):135-42
references.pmid: 17355110
references.citation: BMJ. 2000 Sep 30;321(7264):789-92
references.pmid: 11009515
references.citation: Reprod Biomed Online. 2008 Jun;16(6):842-50
references.pmid: 18549695
references.citation: Rev Hosp Clin Fac Med Sao Paulo. 2003 Mar-Apr;58(2):75-80
references.pmid: 12845359
references.citation: Int J Androl. 2011 Aug;34(4 Pt 2):e86-96; discussion e96-7
references.pmid: 21623831
references.citation: Hum Reprod. 2001 May;16(5):972-8
references.pmid: 11331648
references.citation: Med J Aust. 2006 Oct 16;185(8):414-5
references.pmid: 17137426
references.citation: Hum Reprod. 2000 Sep;15(9):1958-61
references.pmid: 10966994
references.citation: Mod Pathol. 2004 Mar;17(3):316-27
references.pmid: 14976541
references.citation: Oncogenesis. 2014 Apr 21;3:e99
references.pmid: 24752237
references.citation: Mol Cell Endocrinol. 2012 May 22;355(2):192-200
references.pmid: 22210487
references.citation: Lancet. 1993 May 29;341(8857):1392-5
references.pmid: 8098802
references.citation: J Toxicol Sci. 2011;36(6):713-24
references.pmid: 22129735
references.citation: Prostate. 2007 Jun 15;67(9):989-98
references.pmid: 17440938
references.citation: Eur J Cancer. 1991;27(11):1389-92
references.pmid: 1835853
references.citation: Hum Reprod. 1998 Aug;13(8):2041-2
references.pmid: 9756262
references.citation: Cancer Causes Control. 2010 Oct;21(10):1635-43
references.pmid: 20524053
references.citation: Int J Androl. 2003 Apr;26(2):70-5
references.pmid: 12641824
references.citation: Ann Med. 2004;36(8):573-83
references.pmid: 15768829
references.citation: Environ Health Perspect. 2007 Dec;115 Suppl 1:8-14
references.pmid: 18174944
references.citation: Cancer. 2010 May 1;116(9):2140-7
references.pmid: 20309846
references.citation: Br J Cancer. 2014 Mar 18;110(6):1663-72
references.pmid: 24556621
references.citation: Clin Epidemiol. 2013 Oct 17;5:417-27
references.pmid: 24204171
references.citation: Prostate. 2011 Apr;71(5):538-49
references.pmid: 20886540
references.citation: Nat Genet. 2004 May;36(5):497-501
references.pmid: 15064764
references.citation: Hum Reprod. 2008 Aug;23(8):1708-18
references.pmid: 18503055
references.citation: Epigenetics. 2011 Jan;6(1):114-22
references.pmid: 20930529
references.citation: Hum Pathol. 2000 May;31(5):578-83
references.pmid: 10836297
references.citation: Int J Androl. 2008 Feb;31(1):25-30
references.pmid: 17376218
references.citation: J Mol Med (Berl). 2004 May;82(5):317-24
references.pmid: 14985855
references.citation: Cancer Res. 2006 Jun 1;66(11):5624-32
references.pmid: 16740699
references.citation: Br J Cancer. 2013 May 28;108(10):1925-30
references.pmid: 23632485
references.citation: Histopathology. 2012 Jan;60(1):59-74
references.pmid: 22212078
references.citation: Lancet. 2002 Sep 7;360(9335):772-7
references.pmid: 12241836
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Dec;13(12):2157-66
references.pmid: 15598775
references.citation: Eur Urol. 1993;23(1):8-13; discussion 14-5
references.pmid: 8386660
references.citation: Steroids. 1992 Jun;57(6):269-75
references.pmid: 1440697
references.citation: Int J Cancer. 2013 Aug 15;133(4):937-43
references.pmid: 23354735
references.citation: Eur J Clin Invest. 2001 Oct;31(10):880-6
references.pmid: 11737226
references.citation: Int J Oncol. 2004 Apr;24(4):1039-47
references.pmid: 15010846
references.citation: Lancet. 2003 Mar 8;361(9360):859-64
references.pmid: 12642065
references.citation: Development. 2010 Oct;137(19):3177-84
references.pmid: 20724452
references.citation: CA Cancer J Clin. 2002 Mar-Apr;52(2):72-91
references.pmid: 11929007
references.citation: J Natl Cancer Inst. 2004 Jan 21;96(2):145-7
references.pmid: 14734704
references.citation: Int J Androl. 1991 Jun;14(3):179-85
references.pmid: 2066164
references.citation: Endocr Connect. 2013 Sep 17;2(3):R15-29
references.pmid: 23985363
references.citation: Cancer Treat Res. 2007;138:28-49
references.pmid: 18080655
references.citation: Front Endocrinol (Lausanne). 2012 Nov 29;3:150
references.pmid: 23230429
references.citation: Endocr Relat Cancer. 2007 Jun;14(2):257-66
references.pmid: 17639042
references.citation: APMIS. 1998 Jan;106(1):198-204; discussion 204-6
references.pmid: 9524579
references.citation: J Urol. 2000 Apr;163(4):1339-42
references.pmid: 10737540
references.citation: Int J Cancer. 2006 Feb 1;118(3):786-7; author reply 788
references.pmid: 16114016
references.citation: Lancet. 1996 May 11;347(9011):1290-3
references.pmid: 8622504
references.citation: Eur Urol. 2009 Feb;55(2):310-20
references.pmid: 18838208
references.citation: Cell Rep. 2014 Mar 27;6(6):1000-1007
references.pmid: 24630988
references.citation: Cell Death Dis. 2010 Nov 04;1:e94
references.pmid: 21368870
references.citation: Hum Reprod. 2001 Mar;16(3):399-402
references.pmid: 11228202
references.citation: BMC Cancer. 2014 Dec 10;14:930
references.pmid: 25496077
references.citation: J Cell Biochem. 2004 Feb 1;91(2):423-9
references.pmid: 14743400
references.citation: J Hazard Mater. 2013 Apr 15;250-251:115-21
references.pmid: 23435201
references.citation: J Urol. 2007 Oct;178(4 Pt 1):1440-6; discussion 1446
references.pmid: 17706709
references.citation: Bull Acad Natl Med. 2010 Feb;194(2):287-97; discussion 297-300
references.pmid: 21166119
references.citation: J Environ Public Health. 2012;2012:713696
references.pmid: 22991565
references.citation: Int Braz J Urol. 2010 Sep-Oct;36(5):527-36
references.pmid: 21044369
references.citation: Nat Rev Cancer. 2003 Jul;3(7):517-25
references.pmid: 12835671
references.citation: Best Pract Res Clin Endocrinol Metab. 2007 Sep;21(3):462-78
references.pmid: 17875492
references.citation: Cancer. 2008 Feb 15;112(4):919-23
references.pmid: 18181100
references.citation: Genes Dev. 2008 Jan 1;22(1):8-13
references.pmid: 18172160
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references.pmid: 16009939
references.citation: Prostate Cancer. 2011;2011:580318
references.pmid: 22191037
references.citation: Asian Pac J Cancer Prev. 2014;15(2):501-16
references.pmid: 24568454
references.citation: Cancer. 2005 Nov 15;104(10):2255-65
references.pmid: 16228988
references.citation: Int J Androl. 2006 Feb;29(1):228-34
references.pmid: 16371110
references.citation: Mamm Genome. 2001 Feb;12(2):89-94
references.pmid: 11210194
references.citation: Nat Rev Urol. 2014 May;11(5):278-88
references.pmid: 24709963
references.citation: Eur J Cancer. 2002 Oct;38(15):2014-9
references.pmid: 12376206
references.citation: PLoS One. 2011;6(6):e20280
references.pmid: 21674046
references.citation: ANZ J Surg. 2007 Jan-Feb;77(1-2):93-4
references.pmid: 17295832
references.citation: Am Fam Physician. 2000 Nov 1;62(9):2037-44, 2047-8
references.pmid: 11087186
references.citation: Environ Health Perspect. 2006 Aug;114(8):1205-9
references.pmid: 16882526
references.citation: J Urol. 2001 Mar;165(3):837-41
references.pmid: 11176482
references.citation: Hum Mol Genet. 2007 Apr 1;16(7):763-73
references.pmid: 17327269
references.citation: J Biochem. 2007 May;141(5):609-14
references.pmid: 17405795
references.citation: Br J Urol. 1983 Dec;55(6):780-4
references.pmid: 6652452
references.citation: Dev Dyn. 2009 Mar;238(3):664-72
references.pmid: 19191217
references.citation: Am J Anat. 1978 Sep;153(1):1-13
references.pmid: 707305
references.citation: Andrologia. 2012 Feb;44(1):26-33
references.pmid: 21486420
references.citation: J Steroid Biochem Mol Biol. 2011 Oct;127(1-2):102-7
references.pmid: 21397018
references.citation: Prostate. 2008 Apr 1;68(5):517-29
references.pmid: 18220299
references.citation: Br J Cancer. 1995 Feb;71(2):416-20
references.pmid: 7841064
references.citation: Arch Intern Med. 2009 Feb 23;169(4):351-6
references.pmid: 19237718
references.citation: J Clin Endocrinol Metab. 2004 Sep;89(9):4292-7
references.pmid: 15356024
references.citation: Int J Cancer. 2005 Jul 20;115(6):994-7
references.pmid: 15729731
references.citation: Hum Reprod. 2001 Aug;16(8):1768-76
references.pmid: 11473980
references.citation: Cancer Res. 1989 Jul 1;49(13):3474-81
references.pmid: 2731169
references.citation: Environ Health Perspect. 2008 Apr;116(4):566-72
references.pmid: 18414644
references.citation: Microsc Res Tech. 2009 Aug;72(8):603-19
references.pmid: 19319879
references.citation: J Assist Reprod Genet. 2012 Mar;29(3):213-23
references.pmid: 22290605
references.citation: RNA. 2010 Apr;16(4):720-31
references.pmid: 20150330
references.citation: Mutat Res. 2011 May-Jun;727(3):62-71
references.pmid: 21540125
references.citation: Front Genet. 2012 Jul 02;3:120
references.pmid: 22783274
references.citation: Biol Reprod. 2005 Sep;73(3):427-33
references.pmid: 15901636
references.citation: Am J Epidemiol. 1988 May;127(5):1013-8
references.pmid: 2895979
references.citation: Fertil Steril. 2012 Feb;97(2):267-74
references.pmid: 22289286
references.citation: Front Biosci (Schol Ed). 2012 Jun 01;4(4):1266-74
references.pmid: 22652870
references.citation: BMJ. 1999 Feb 27;318(7183):559-62
references.pmid: 10037628
references.citation: Cancer Genet Cytogenet. 2004 Jun;151(2):93-138
references.pmid: 15172750
references.citation: J Urol. 2011 Jan;185(1):126-31
references.pmid: 21074214
references.citation: J Toxicol Environ Health B Crit Rev. 2008 Mar;11(3-4):322-44
references.pmid: 18368559
references.citation: Best Pract Res Clin Endocrinol Metab. 2006 Mar;20(1):45-61
references.pmid: 16522519
references.citation: Am J Pathol. 2000 Jan;156(1):347-53
references.pmid: 10623684
references.citation: N Engl J Med. 2003 Jul 17;349(3):215-24
references.pmid: 12824459
references.citation: Asian Pac J Cancer Prev. 2007 Apr-Jun;8(2):275-8
references.pmid: 17696745
references.citation: Cytogenet Genome Res. 2006;113(1-4):292-9
references.pmid: 16575192
references.citation: Nat Struct Mol Biol. 2010 Oct;17(10):1169-74
references.pmid: 20924405
references.citation: Cancer Metastasis Rev. 2002;21(1):3-16
references.pmid: 12400993
references.citation: Int J Androl. 2011 Aug;34(4 Pt 2):e37-48
references.pmid: 21366607
references.citation: Genes Dev. 2003 Mar 1;17(5):603-14
references.pmid: 12629043
references.citation: J Clin Endocrinol Metab. 2004 Jul;89(7):3161-7
references.pmid: 15240588
references.citation: J Natl Cancer Inst. 2008 Feb 6;100(3):170-83
references.pmid: 18230794
references.citation: J Pathol. 2007 Nov;213(3):319-28
references.pmid: 17893849
references.citation: Hum Genet. 1991 May;87(1):81-3
references.pmid: 2037286
references.citation: J Natl Cancer Inst. 1990 Mar 7;82(5):412-8
references.pmid: 2304089
references.citation: Fertil Steril. 2004 Jan;81(1):205-9
references.pmid: 14711569
references.citation: Oncol Rep. 2007 Jul;18(1):127-32
references.pmid: 17549357
references.citation: PLoS One. 2007 Dec 12;2(12):e1289
references.pmid: 18074014
references.citation: Birth Defects Res A Clin Mol Teratol. 2012 Jul;94(7):499-510
references.pmid: 22678668
references.citation: Science. 2005 Jun 3;308(5727):1466-9
references.pmid: 15933200
references.citation: Am J Epidemiol. 2003 May 1;157(9):800-14
references.pmid: 12727674
references.citation: J Clin Oncol. 1999 Jan;17(1):173-9
references.pmid: 10458231
references.citation: Cancer Res. 1989 Dec 1;49(23):6471-3
references.pmid: 2819706
references.citation: Anticancer Res. 2014 Jun;34(6):2709-13
references.pmid: 24922631
references.citation: J Natl Cancer Inst. 2005 Aug 17;97(16):1204-10
references.pmid: 16106025
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Int J Cancer. 2000 Aug 1;87(3):438-43
references.pmid: 10897052
references.citation: APMIS. 2003 Jan;111(1):161-71; discussion 172-3
references.pmid: 12752258
references.citation: Int J Dev Biol. 2013;57(2-4):225-39
references.pmid: 23784834
references.citation: Hum Reprod. 2000 Jun;15(6):1289-94
references.pmid: 10831557
references.citation: Hum Reprod Update. 2012 Jan-Feb;18(1):44-59
references.pmid: 21989172
references.citation: Int J Androl. 2011 Aug;34(4 Pt 2):e133-50; discussion e150-1
references.pmid: 21651573
references.citation: Endocrinology. 2012 Sep;153(9):4097-110
references.pmid: 22733974
references.citation: Curr Opin Cell Biol. 2007 Jun;19(3):257-65
references.pmid: 17467256
references.citation: Cancer Invest. 2008 Feb;26(1):74-80
references.pmid: 18181049
references.citation: Cancer Causes Control. 2005 Aug;16(6):651-6
references.pmid: 16049803