Abstract
Discrepancies in adverse trends in male reproductive health around the world are due in part to the difficulty of comparing studies from different time periods with distinct study populations and varied clinical definitions and diagnostic criteria for these processes. In this context, the apparent increase in the incidence of cryptorchidism and hypospadias in the Western world over recent decades, with a leveling off in hypospadias incidence in most European countries during the 1980s, can be questioned due to differences in case definitions, age at diagnosis, examination techniques, and study populations, e.g., registry versus cohort studies. Experimental investigations have supported the hypothesis of a link between environmental factors and urogenital tract malformations, suggesting that cryptorchidism and hypospadias are associated with exposure to environmental chemicals, especially those identified as endocrine-disrupting chemicals (EDCs). Exposure to EDCs during pregnancy may play a role in the development of male sexual disorders because sexual differentiation and reproductive functioning are critically dependent on the ratio of androgens to estrogens, and an imbalance in this ratio may be responsible for male congenital anomalies. Epidemiology studies have also indicated a link between EDCs and malformations. The accumulated evidence appears sufficient to endorse a precautionary approach, with the implementation of measures to reduce community exposure to EDCs, especially in women of childbearing age, both before and during pregnancy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Skakkebæk NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001;16(5):972–8.
Itoh N, Kayama F, Tatsuki J, Tsukamoto T. Have sperm counts deteriorated over the past 20 years in healthy, young Japanese men? Results from the Sapporo area. J Androl. 2001;22:40–4.
Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette Jr LJ, et al. Male reproductive health and environmental xenoestrogens. Environ Health Perspect. 1996;104:741–803.
Akre O, Lipworth L, Cnattingius S, Sparen P, Ekbom A. Risk factor patterns for cryptorchidism and hypospadias. Epidemiology. 1999;10(4):364–9.
Weidner IS, Moller H, Jensen TK, Skakkebaek N. Cryptorchidism and hypospadias in sons of gardeners and farmers. Environ Health Perspect. 1998;106:793–6.
Boisen KA, Kaleva M, Main KM, Virtanen HE, Haavisto A-M, Schmidt IM, et al. Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet. 2004;363:1264–9.
Lund L, Engebjerg MC, Pedersen L, Ehrenstein V, Nørgaard M, Sørensen HT. Prevalence of hypospadias in Danish boys: a longitudinal study, 1977–2005. Eur Urol. 2009;55(5):1022–6.
Paulozzi LJ. International trends in rates of hypospadias and cryptorchidism. Environ Health Perspect. 1999;107:297–302.
Toppari J, Kaleva M, Virtanen HE. Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data. Hum Reprod Update. 2001;7(3):282–6.
Martinez-Frias ML, Prieto D, Prieto L, Bermejo E, Rodriguez-Pinilla E, Cuevas L. Secular decreasing trend of the frequency of hypospadias among newborn male infants in Spain. Birth Defects Res A Clin Mol Teratol. 2004;70:75–81.
Virtanen HE, Toppari J. Epidemiology and pathogenesis of cryptorchidism. Hum Reprod Update. 2008;14(1):49–58.
Acerini CL, Miles HL, Dunger DB, Ong KK, Hughes IA. The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort. Arch Dis Child. 2009;94:868–72.
Preiksa RT, Zilaitien B, Matulevicius V, Skakkebaek NE, Petersen JH, Jorgensen N, et al. Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod. 2005;20:1928–32.
Boisen KA, Chellakooty M, Schmidt IM, Kai CM, Damgaard IN, Suomi AM, et al. Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at 3 months of age. J Clin Endocrinol Metab. 2005;90:4041–6.
Colborn T, Clement C. Wingspread consensus statement. Chemically induced alterations in sexual, functional development: the wildlife/human connection. Princeton: Princeton Scientific; 1992. p. 1–8.
Porta M, Puigdomènech E, Ballester F, Selva J, Ribas-Fitó N, DomÃnguez-Boada L, et al. Studies conducted in Spain on concentrations in humans of persistent toxic compounds. Gac Sanit. 2008;22(3):248–66. Review.
Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Olea-Serrano MF. The E-Screen as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995;103:113–22.
Gray LE, Ostby J, Monosson E, Klece WR. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health. 1999;15:48–64.
Sohoni P, Sumpter JP. Several environmental oestrogens are also antiandrogens. J Endocrinol. 1998;158:327–39.
Sultan C, Balaguer P, Terouanne B, Georget V, Paris F, Jeandel C, et al. Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation. Mol Cell Endocrinol. 2001;178:99–105.
Olea N, Olea-Serrano F, Lardelli-Claret P, Rivas A, Barba-Navarro A. Inadvertent exposure to xenoestrogens in children. Toxicol Ind Health. 1999;15:151–8.
Dolk H, Vrijheid M. The impact of environmental pollution on congenital anomalies. Br Med Bull. 2003;68:25–45.
Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005;113:1056–61.
Krimsky S. Hormonal chaos: the scientific and social origins of the environmental endocrine hypothesis. Baltimore: Johns Hopkins University; 2000.
Lopez-Espinosa MJ, Granada A, Carreno J, Salvatierra M, Olea-Serrano F, et al. Organochlorine pesticides in placentas from Southern Spain and some related factors. Placenta. 2007;28(7):631–8.
Christiansen S, Scholze M, Axelstad M, Boberg J, Kortenkamp A, Hass U. Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat. Int J Androl. 2008;31(2):241–8.
Kortenkamp A. Low dose mixture effects of endocrine disrupters: implications for risk assessment and epidemiology. Int J Androl. 2008;31(2):233–40.
Almstrup K, Fernandez MF, Petersen JH, Olea N, Skakkebaek NE, Leffers H. Dual effects of phytoestrogens result in u-shaped dose-response curves. Environ Health Perspect. 2002;110:743–8.
Weltje L, vom Saal FS, Oehlmann J. Reproductive stimulation by low doses of xenoestrogens contrasts with the view of hormesis as an adaptive response. Hum Exp Toxicol. 2005;24:431–7.
Fernandez MF, Olmos B, Granada A, López-Espinosa MJ, Molina-Molina JM, Fernandez JM, et al. Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study. Environ Health Perspect. 2007;115 Suppl 1:8–14.
Kristensen P, Irgens LM, Andersen A, Bye AS, Sundheim L. Birth defects among offspring of Norwegian farmers. Epidemiology. 1997;8:537–44.
Garcia AM, Flecher T, Benavides FG, Orts E. Parental agricultural work and selected congenital malformations. Am J Epidemiol. 1999;149:64–74.
Rueda-Domingo MT, Lopez-Navarrete E, Nogueras-Ocaña M, Lardelli-Claret P. Factores de riesgo de criptorquidia. Gac Sanit. 2001;15:398–405.
Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, et al. Cryptorchidism and hypospadias in the Sicilian district of Ragusa and the use of pesticides. Reprod Toxicol. 2006;22(1):8–12.
Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L, et al. The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. Int J Androl. 2007;30(1):3–13.
Andersen HR, Schmidt IM, Grandjean P, Jensen TK, Budtz-Jørgensen E, Kjaerstad MB, et al. Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy. Environ Health Perspect. 2008;116(4):566–72.
Zhu JL, Hjollund NH, Andersen AM, Olsen J. Occupational exposure to pesticides and pregnancy outcomes in gardeners and farmers: a study within the Danish National Birth Cohort. J Occup Environ Med. 2006;48(4):347–52.
Irgens A, Kruger K, Skorve AH, Irgens LM. Birth defects and paternal occupational exposure. Hypotheses tested in a record linkage based data set. Acta Obstet Gynecol Scand. 2000;79:465–70.
Olshan AF, Teschke K, Baird PA. Paternal occupation and congenital anomalies in offspring. Am J Ind Med. 1991;20:447–75.
Garcia-Rodriguez J, Garcia-Martin M, Nogueras-Ocaña M, de Dios Luna-del-Castillo J, Espigares Garcia M, Olea N, et al. Exposure to pesticides and cryptorchidism: geographical evidence of a possible association. Environ Health Perspect. 1996;104:1090–5.
Restrepo M, Muñoz N, Day N, Parra JE, Hernandez C, Blettner M, et al. Birth defects among children born to a population occupationally exposed to pesticides in Colombia. Scand J Work Environ Health. 1990;16:239–46.
Pierik FH, Burdorf A, Deddens JA, Juttmann RE, Weber RFA. Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Environ Health Perspect. 2004;112:1570–6.
Van Tongeren M, Nieuwenhuijsen MJ, Gardiner K, Armstrong B, Vrijheid M, Dolk H, et al. A job-exposure matrix for potential endocrine-disrupting chemicals developed for a study into the association between maternal occupation and hypospadias. Ann Occup Hyg. 2002;46:465–77.
Vrijheid M, Armstrong B, Dolk H, van Tongeren M, Botting B. Risk of hypospadias in relation to maternal occupational exposure to potential endocrine disrupting chemicals. Occup Environ Med. 2003;60:543–50.
Ormond G, Nieuwenhuijsen MJ, Nelson P, Toledano MB, Iszatt N, Geneletti S, et al. Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ Health Perspect. 2009;117(2):303–7.
Dolk H, Vrijheid M, Armstrong B, Abramsky L, Bianchi F, Garne E, et al. Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study. Lancet. 1998;352:423–7.
Hosie S, Loff S, Witt K, Niessen K, Waag KL. Is there a correlation between organochlorine compounds and undescended testes? Eur J Pediatr Surg. 2000;10:304–9.
Longnecker MP, Klebanoff MA, Brock JW, Zhou H, Gray KA, Needham LL, et al. Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring. Am J Epidemiol. 2002;155:313–22.
Bhatia R, Shiau R, Petreas M, Weintraub JM, Farhang L, Eskenazi B. Organochlorine pesticides and male genital anomalies in the child health and development studies. Environ Health Perspect. 2005;113:220–4.
Damgaard IN, Skakkebaek NE, Toppari J, Virtanen HE, Shen H, Schramm KW, et al. Persistent pesticides in human breast milk and cryptorchidism. Environ Health Perspect. 2006;114(7):1133–8.
Main KM, Kiviranta H, Virtanen HE, Sundqvist E, Tuomisto JT, Tuomisto J, et al. Flame retardants in placenta and breast milk and cryptorchidism in newborn boys. Environ Health Perspect. 2007;115(10):1519–26.
Shen H, Main KM, Andersson AM, Damgaard IN, Virtanen HE, Skakkebaek NE, et al. Concentrations of persistent organochlorine compounds in human milk and placenta are higher in Denmark than in Finland. Hum Reprod. 2008;23(1):201–10.
Brucker-Davis F, Wagner-Mahler K, Delattre I, Ducot B, Ferrari P, Bongain A, et al. Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations. Hum Reprod. 2008;23(8):1708–18.
Palmer JR, Herbst AL, Noller KL, Boggs DA, Troisi R, Titus-Ernstoff L, et al. Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environ Health. 2009;8:37.
Palmer JR, Wise LA, Robboy SJ, Titus-Ernstoff L, Noller KL, Herbst AL, et al. Hypospadias in sons of women exposed to diethylstilbestrol in utero. Epidemiology. 2005;16(4):583–6.
Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A, et al. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ Health Perspect. 2009;117(12):1839–46.
Additional References
European science foundation. Male reproductive health. http://www.esf.org/publications/science-policy-briefings.html
Fernández MF, Rivas A, Olea-Serrano F, Cerrillo I, Molina-Molina JM, Araque P, et al. Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect. Anal Bioanal Chem. 2004;379(1):163–70.
Main KM, Skakkebaek NE, Virtanen HE, Toppari J. Genital anomalies in boys and the environment. Best Pract Res Clin Endocrinol Metab. 2010;24(2):279–89. Review.
Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias trends in two American surveillance systems. Pediatrics. 1997;100:831–4.
Robaire B, Hales BF. Mechanism of action of cyclophosphamide as a malemediated developmental toxicant. Adv Exp Med Biol. 2003;518:169–80.
Weidner IS, Møller H, Jensen TK, Skakkebæk NE. Risk factors for cryptorchidism and hypospadias. J Urol. 1999;161(5):1606–9.
Acknowledgments
We are indebted to Richard Davies for editorial assistance. This study was supported by grants from the Junta de AndalucÃa (grant numbers P09-CTS-5488 and SAS 07/0133), Spanish Ministry of Science and Innovation (Ramón y Cajal Programme to MF. Fernandez), Spanish Ministry of Health (CIBERESP), and the European Union Commission (Environ. Reprod. Health, QLK4-1999-01422; EDEN, QLRT-2001-00603; CASCADE, Food-CT-2003-506319; and CONTAMED, 2009-212502, projects).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Fernandez, M.F., Olea, N. (2012). Developmental Exposure to Endocrine Disruptors and Male Urogenital Tract Malformations. In: Diamanti-Kandarakis, E., Gore, A. (eds) Endocrine Disruptors and Puberty. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-60761-561-3_8
Download citation
DOI: https://doi.org/10.1007/978-1-60761-561-3_8
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-60761-560-6
Online ISBN: 978-1-60761-561-3
eBook Packages: MedicineMedicine (R0)