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Internal exposure to pollutants and sex hormone levels in Flemish male adolescents in a cross-sectional study: associations and dose–response relationships

Journal of Exposure Science & Environmental Epidemiology volume 21, pages 106–113 (2011)Cite this article

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Abstract

Flanders is densely populated with much industry and intensive farming. Hormonal status of 14- to 15-year-old male adolescents was studied in relation to internal exposure to pollutants. A total of 887 participants were selected as a random sample of the adolescents residing in the study areas. Confounding factors and significant covariates were taken into account. Serum levels of testosterone, free testosterone and estradiol, and the aromatase index showed significant positive associations with serum levels of marker polychlorobiphenyls (sum of PCBs 138, 153, and 180) and of hexachlorobenzene (HCB) and a negative association with urinary cadmium concentration. Serum levels of estradiol also showed a positive association with serum levels of dichlorodiphenyldichloroethylene (DDE). A doubling of serum concentrations of marker PCBs and HCB and of urinary concentration of cadmium were, respectively, associated with an increase of 16.4% (P<0.00001) and 16.6% (P<0.001) and a decrease of 9.6% (P<0.001) in serum testosterone concentration. Similar findings were made after additional adjustment for concurrent exposures. Associations between biological effects and internal exposures were, in terms of the regression coefficient, often stronger at exposures below the median. Environmental exposures to pollutants resulting in “normal” levels of internal exposure were associated with quite substantial differences in hormone concentrations.

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References

  • Ahmad S.U., Tariq S., Jalali S., and Ahmad M.M. Environmental pollutant Aroclor 1242 (PCB) disrupts reproduction in adult male rhesus monkeys (Macaca mulatta). Environ Res 2003: 93 (3): 272–278.

    Article  CAS  PubMed  Google Scholar 

  • Alvarez L., Randi A., Alvarez P., Piroli G., Chamson-Reig A., and Lux-Lantos V., et al. Reproductive effects of hexachlorobenzene in female rats. J Appl Toxicol 2000: 20 (1): 81–87.

    Article  CAS  PubMed  Google Scholar 

  • Bilau M., Matthys C., Baeyens W., Bruckers L., De B.G., and Den H.E., et al. Dietary exposure to dioxin-like compounds in three age groups: results from the Flemish environment and health study. Chemosphere 2008: 70 (4): 584–592.

    Article  CAS  PubMed  Google Scholar 

  • Bonefeld-Jorgensen E.C., Andersen H.R., Rasmussen T.H., and Vinggaard A.M. Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity. Toxicology 2001: 158 (3): 141–153.

    Article  CAS  PubMed  Google Scholar 

  • Castano E., and Flores-Saaib R.D. A mathematical approach for the transactivation of hERalpha. Philos Transact A Math Phys Eng Sci 2008: 366 (1874): 2253–2263.

    Article  CAS  Google Scholar 

  • Covaci A., Voorspoels S., Thomsen C., van B.B., and Neels H. Evaluation of total lipids using enzymatic methods for the normalization of persistent organic pollutant levels in serum. Sci Total Environ 2006: 366 (1): 361–366.

    Article  CAS  PubMed  Google Scholar 

  • Croes K., Baeyens W., Bruckers L., Den H.E., Koppen G., and Nelen V., et al. Hormone levels and sexual development in Flemish adolescents residing in areas differing in pollution pressure. Int J Hyg Environ Health 2009: 212 (6): 612–625.

    Article  CAS  PubMed  Google Scholar 

  • Delbes G., Levacher C., Duquenne C., Racine C., Pakarinen P., and Habert R. Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor alpha. Endocrinology 2005: 146 (5): 2454–2461.

    Article  CAS  PubMed  Google Scholar 

  • Endo F., Monsees T.K., Akaza H., Schill W.B., and Pflieger-Bruss S. Effects of single non-ortho, mono-ortho, and di-ortho chlorinated biphenyls on cell functions and proliferation of the human prostatic carcinoma cell line, LNCaP. Reprod Toxicol 2003: 17 (2): 229–236.

    Article  CAS  PubMed  Google Scholar 

  • Eskenazi B., Warner M., Marks A.R., Samuels S., Gerthoux P.M., and Vercellini P., et al. Serum dioxin concentrations and age at menopause. Environ Health Perspect 2005: 113 (7): 858–862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foster W.G., McMahon A., Younglai E.V., Jarrell J.F., and Lecavalier P. Alterations in circulating ovarian steroids in hexachlorobenzene-exposed monkeys. Reprod Toxicol 1995: 9 (6): 541–548.

    Article  CAS  PubMed  Google Scholar 

  • Gregoraszczuk E.L., Grochowalski A., Chrzaszcz R., and Wegiel M. Congener-specific accumulation of polychlorinated biphenyls in ovarian follicular wall follows repeated exposure to PCB 126 and PCB 153. Comparison of tissue levels of PCB and biological changes. Chemosphere 2003: 50 (4): 481–488.

    Article  CAS  PubMed  Google Scholar 

  • Guillette Jr L.J., and Gunderson M.P. Alterations in development of reproductive and endocrine systems of wildlife populations exposed to endocrine-disrupting contaminants. Reproduction 2001: 122 (6): 857–864.

    Article  CAS  PubMed  Google Scholar 

  • Gunnarsson D., Svensson M., Selstam G., and Nordberg G. Pronounced induction of testicular PGF(2 alpha) and suppression of testosterone by cadmium-prevention by zinc. Toxicology 2004: 200 (1): 49–58.

    Article  CAS  PubMed  Google Scholar 

  • Hagmar L., Bjork J., Sjodin A., Bergman A., and Erfurth E.M. Plasma levels of persistent organohalogens and hormone levels in adult male humans. Arch Environ Health 2001: 56 (2): 138–143.

    Article  CAS  PubMed  Google Scholar 

  • Handelsman D.J. Indirect androgen doping by oestrogen blockade in sports. Br J Pharmacol 2008: 154 (3): 598–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu P.C., Lai T.J., Guo N.W., Lambert G.H., and Leon G.Y. Serum hormones in boys prenatally exposed to polychlorinated biphenyls and dibenzofurans. J Toxicol Environ Health A 2005: 68 (17–18): 1447–1456.

    Article  CAS  PubMed  Google Scholar 

  • Kaya H., Hany J., Fastabend A., Roth-Harer A., Winneke G., and Lilienthal H. Effects of maternal exposure to a reconstituted mixture of polychlorinated biphenyls on sex-dependent behaviors and steroid hormone concentrations in rats: dose–response relationship. Toxicol Appl Pharmacol 2002: 178 (2): 71–81.

    Article  CAS  PubMed  Google Scholar 

  • Kelce W.R., Stone C.R., Laws S.C., Gray L.E., Kemppainen J.A., and Wilson E.M. Persistent DDT metabolite p,p′-DDE is a potent androgen receptor antagonist. Nature 1995: 375 (6532): 581–585.

    Article  CAS  PubMed  Google Scholar 

  • Kruger T., Ghisari M., Hjelmborg P.S., Deutch B., and Bonefeld-Jorgensen E.C. Xenohormone transactivities are inversely associated to serum POPs in Inuit. Environ Health 2008: 7: 38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li L., Andersen M.E., Heber S., and Zhang Q. Non-monotonic dose–response relationship in steroid hormone receptor-mediated gene expression. J Mol Endocrinol 2007: 38 (5): 569–585.

    Article  CAS  PubMed  Google Scholar 

  • Lilienthal H., Hack A., Roth-Harer A., Grande S.W., and Talsness C.E. Effects of developmental exposure to 2,2,4,4,5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in rats. Environ Health Perspect 2006: 114 (2): 194–201.

    Article  CAS  PubMed  Google Scholar 

  • Machala M., Neca J., Drabek P., Ulrich R., Sabatova V., and Nezveda K., et al. Effects of chronic exposure to PCBs on cytochrome P450 systems and steroidogenesis in liver and testis of bulls (Bos taurus). Comp Biochem Physiol A Mol Integr Physiol 1998: 120 (1): 65–70.

    Article  CAS  PubMed  Google Scholar 

  • Martin M.B., Reiter R., Pham T., Avellanet Y.R., Camara J., and Lahm M., et al. Estrogen-like activity of metals in MCF-7 breast cancer cells. Endocrinology 2003: 144 (6): 2425–2436.

    Article  CAS  PubMed  Google Scholar 

  • Martin M.B., Voeller H.J., Gelmann E.P., Lu J., Stoica E.G., and Hebert E.J., et al. Role of cadmium in the regulation of AR gene expression and activity. Endocrinology 2002: 143 (1): 263–275.

    Article  CAS  PubMed  Google Scholar 

  • Meeker J.D., Rossano M.G., Protas B., Padmanahban V., Diamond M.P., and Puscheck E., et al. Environmental exposure to metals and male reproductive hormones: circulating testosterone is inversely associated with blood molybdenum. Fertil Steril 2009 e-pub ahead of print 6 November 2008. doi: 10.1016/j.fcrtnstcrt.2008.09.044.

  • Menke A., Guallar E., Shiels M.S., Rohrmann S., Basaria S., and Rifai N., et al. The association of urinary cadmium with sex steroid hormone concentrations in a general population sample of US adult men. BMC Public Health 2008: 8: 72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mol N.M., Sorensen N., Weihe P., Andersson A.M., Jorgensen N., and Skakkebaek N.E., et al. Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls. Eur J Endocrinol 2002: 146 (3): 357–363.

    Article  CAS  PubMed  Google Scholar 

  • Murugesan P., Kanagaraj P., Yuvaraj S., Balasubramanian K., Aruldhas M.M., and Arunakaran J. The inhibitory effects of polychlorinated biphenyl Aroclor 1254 on Leydig cell LH receptors, steroidogenic enzymes and antioxidant enzymes in adult rats. Reprod Toxicol 2005: 20 (1): 117–126.

    Article  CAS  PubMed  Google Scholar 

  • Murugesan P., Muthusamy T., Balasubramanian K., and Arunakaran J. Polychlorinated biphenyl (Aroclor 1254) inhibits testosterone biosynthesis and antioxidant enzymes in cultured rat Leydig cells. Reprod Toxicol 2008: 25 (4): 447–454.

    Article  CAS  PubMed  Google Scholar 

  • Oskam I.C., Lyche J.L., Krogenaes A., Thomassen R., Skaare J.U., and Wiger R., et al. Effects of long-term maternal exposure to low doses of PCB126 and PCB153 on the reproductive system and related hormones of young male goats. Reproduction 2005: 130 (5): 731–742.

    Article  CAS  PubMed  Google Scholar 

  • Oskam I.C., Ropstad E., Dahl E., Lie E., Derocher A.E., and Wiig O., et al. Organochlorines affect the major androgenic hormone, testosterone, in male polar bears (Ursus maritimus) at Svalbard. J Toxicol Environ Health A 2003: 66 (22): 2119–2139.

    Article  CAS  PubMed  Google Scholar 

  • Park H., Lee S.J., Kang J.H., and Chang Y.S. Congener-specific approach to human PCB concentrations by serum analysis. Chemosphere 2007: 68 (9): 1699–1706.

    Article  CAS  PubMed  Google Scholar 

  • Ralph J.L., Orgebin-Crist M.C., Lareyre J.J., and Nelson C.C. Disruption of androgen regulation in the prostate by the environmental contaminant hexachlorobenzene. Environ Health Perspect 2003: 111 (4): 461–466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rylander L., Wallin E., Jonssson B.A., Stridsberg M., Erfurth E.M., and Hagmar L. Associations between CB-153 and p,p′-DDE and hormone levels in serum in middle-aged and elderly men. Chemosphere 2006: 65 (3): 375–381.

    Article  CAS  PubMed  Google Scholar 

  • Sanford L.M. Evidence that estrogen regulation of testosterone secretion in adult rams is mediated by both indirect (gonadotropin dependent) and direct (gonadotropin independent) means. J Androl 1985: 6 (5): 306–314.

    Article  CAS  PubMed  Google Scholar 

  • Schroijen C., Baeyens W., Schoeters G., Den H.E., Koppen G., and Bruckers L., et al. Internal exposure to pollutants measured in blood and urine of Flemish adolescents in function of area of residence. Chemosphere 2008: 71 (7): 1317–1325.

    Article  CAS  PubMed  Google Scholar 

  • Sheehan D.M., Willingham E., Gaylor D., Bergeron J.M., and Crews D. No threshold dose for estradiol-induced sex reversal of turtle embryos: how little is too much? Environ Health Perspect 1999: 107 (2): 155–159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinberger A., and Klinefelter G. Sensitivity of Sertoli and Leydig cells to xenobiotics in in vitro models. Reprod Toxicol 1993: 7 (Suppl 1): 23–37.

    Article  CAS  PubMed  Google Scholar 

  • Stoica A., Katzenellenbogen B.S., and Martin M.B. Activation of estrogen receptor-alpha by the heavy metal cadmium. Mol Endocrinol 2000: 14 (4): 545–553.

    CAS  PubMed  Google Scholar 

  • Turyk M.E., Anderson H.A., Freels S., Chatterton Jr R., Needham L.L., and Patterson Jr D.G., et al. Associations of organochlorines with endogenous hormones in male Great Lakes fish consumers and nonconsumers. Environ Res 2006: 102 (3): 299–307.

    Article  CAS  PubMed  Google Scholar 

  • Ukkola O., Gagnon J., Rankinen T., Thompson P.A., Hong Y., and Leon A.S., et al. Age, body mass index, race and other determinants of steroid hormone variability: the HERITAGE Family Study. Eur J Endocrinol 2001: 145 (1): 1–9.

    Article  CAS  PubMed  Google Scholar 

  • Vermeulen A., Kaufman J.M., and Giagulli V.A. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab 1996: 81 (5): 1821–1826.

    CAS  PubMed  Google Scholar 

  • Zeng X., Jin T., Buchet J.P., Jiang X., Kong Q., and Ye T., et al. Impact of cadmium exposure on male sex hormones: a population-based study in China. Environ Res 2004: 96 (3): 338–344.

    Article  CAS  PubMed  Google Scholar 

  • Zeng X., Lin T., Zhou Y., and Kong Q. Alterations of serum hormone levels in male workers occupationally exposed to cadmium. J Toxicol Environ Health A 2002: 65 (7): 513–521.

    Article  CAS  PubMed  Google Scholar 

  • Zitzmann M., and Nieschlag E. Testosterone levels in healthy men and the relation to behavioural and physical characteristics: facts and constructs. Eur J Endocrinol 2001: 144 (3): 183–197.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Marc Elskens and Tim Nawrot (statistics) and Hans Keune and Ilse Loots (communication) for advice. We gratefully acknowledge the collaboration of the 42 Flemish schools, the (psycho-medical) centers for guidance of pupils, all participating adolescents and their parents. The study was commissioned, financed, and steered by the Ministry of the Flemish Community (Department of Science, Department of Public Health and Department of Environment), without any responsibility for the scientific content.

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Authors and Affiliations

  1. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

    Willem Dhooge

  2. Environmental Toxicology, Flemish Institute of Technological Research, Mol, Belgium

    Elly Den Hond, Gudrun Koppen & Greet Schoeters

  3. University of Hasselt, Diepenbeek, Belgium

    Liesbeth Bruckers

  4. Provincial Institute of Hygiene, Antwerp, Belgium

    Vera Nelen & Els van de Mieroop

  5. Department of Public Health, Ghent University, Ghent, Belgium

    Maaike Bilau

  6. Analytical and Environmental Chemistry (ANCH), Vrije Universiteit Brussel, Brussels, Belgium

    Kim Croes & Willy Baeyens

  7. Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

    Greet Schoeters

  8. Department of Radiotherapy, Study Centre for Carcinogenesis and Primary Prevention of Cancer, Nuclear Medicine and Experimental Cancerology, Ghent University, Ghent, Belgium

    Nicolas van Larebeke

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  1. Willem Dhooge
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Correspondence to Nicolas van Larebeke.

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Dhooge, W., Den Hond, E., Koppen, G. et al. Internal exposure to pollutants and sex hormone levels in Flemish male adolescents in a cross-sectional study: associations and dose–response relationships. J Expo Sci Environ Epidemiol 21, 106–113 (2011). https://doi.org/10.1038/jes.2009.63

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