Blood metal levels and serum testosterone concentrations in male and female children and adolescents: NHANES 2011–2012

Autoři: Qi Yao aff001;  Ge Zhou aff002;  Meilin Xu aff003;  Jianguo Dai aff001;  Ziwei Qian aff001;  Zijing Cai aff001;  Luyao Zhang aff001;  Yong Tan aff002;  Rongkui Hu aff002
Působiště autorů: Department of Pathology and Pathophysiology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China aff001;  Department of Reproductive Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu Province, China aff002;  Medical department life science China, GE healthcare China, Beijing, China aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224892


Environmental exposure to metals is ubiquitous, but its relation to androgen hormone levels is not well understood, especially in children and adolescents. This study aimed to explore the relationship between blood metal concentrations (lead, cadmium, total mercury, selenium, and manganese) and serum total testosterone (TT) levels in 6–19-year-old children and adolescents in the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Weighted multivariable linear regression models using NHANES sampling weights were employed to evaluate the association between log-transformed serum TT and each metal categories in male and female children (age 6-11years) and adolescents (age 12–19 years). We established that blood cadmium and manganese levels were associated with significantly higher serum TT levels in the female adolescents. Additionally, the blood selenium levels in male adolescents were related to significantly higher serum TT. No significant associations between blood lead or total mercury levels and TT were observed in children or adolescents of either sex. These findings suggest that environmental exposure to certain metals could affect serum TT levels in adolescents, which might have important implications for the health of adolescents. Further research is required to confirm and extend our present findings.

Klíčová slova:

Adolescents – Blood – Cadmium – Manganese – Metallic lead – Selenium – Testosterone – Metallic mercury


1. Surampudi PN, Wang C, Swerdloff R. Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy. Int J Endocrinol. 2012; 2012: 625434. doi: 10.1155/2012/625434 22505891

2. Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009; 5(3): 427–448. doi: 10.2147/tcrm.s3025 19707253

3. Pluchino N, Carmignani A, Cubeddu A, Santoro A, Cela V, Errasti T. Androgen therapy in women: for whom and when. Arch Gynecol Obstet. 2013; 288(4): 731–737. doi: 10.1007/s00404-013-2969-7 23912530

4. Davis SR, Wahlin-Jacobsen S. Testosterone in women—e clinical significance. Lancet Diabetes Endocrinol. 2015; 3(12): 980–992. doi: 10.1016/S2213-8587(15)00284-3 26358173

5. Carlsen E, Giwercman A, Keiding N, Sakkkebaek NE. Evidence for decreasing quality of semen during past 50 years.BMJ. 1992; 305(6854): 609–613. doi: 10.1136/bmj.305.6854.609 1393072

6. Rolland M, Le Moal J, Wagner V, Royère D, thDeMouzon J. Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and 2005 in France. Hum Reprod. 2013; 28(2): 462–470. doi: 10.1093/humrep/des415 23213178

7. Main KM, Skakkebaek NE, Virtanen HE, Toppari J. Genital anomalies in boys and the environment. Best Pract Res Clin Endocrinol Metab. 2010; 24(2): 279–289. doi: 10.1016/j.beem.2009.10.003 20541152

8. Euling SY, Herman-Giddens ME, Lee PA, Selevan SG, Juul A, Sørensen TI, et al. Examination of US puberty-timing data from 1940 to 1994 for secular trends: panel findings. Pediatrics. 2008; 121 (Suppl 3): S172–191.

9. Zawatski W, Lee MM. Male pubertal development: are endocrine-disrupting compounds shifting the norms? J Endocrinol. 2013; 182(2):R1–R12.

10. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018; 14(5): 270–284. doi: 10.1038/nrendo.2018.24 29569621

11. Klap J, Schmid M, Loughlin KR. The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy. J Urol. 2015; 193(2): 403–413. doi: 10.1016/j.juro.2014.07.123 25260832

12. Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst. 1996; 88(16): 1118–1126. doi: 10.1093/jnci/88.16.1118 8757191

13. Cole TJ, Ahmed ML, Preece MA, Hindmarsh P, Dunger DB. The relationship between Insulin-like Growth Factor 1, sex steroids and timing of the pubertal growth spurt. Clin Endocrinol (Oxf). 2015; 82(6): 862–869.

14. Cabrera SM, Rogol AD. Testosterone exposure in childhood: discerning pathology from physiology. Expert Opin Drug Saf. 2013; 12(3): 375–388. doi: 10.1517/14740338.2013.782000 23517636

15. Jurasovic J., Cvitkovic P., Pizent A., Colak B., Telisman S. Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male subjects. Biometals. 2004; 17, 735–743. 15689116

16. Ali I, Engström A, Vahter M, Skerfving S, Lundh T, Lidfeldt J, et al. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women. Environ Res. 2014; 134:265–269. doi: 10.1016/j.envres.2014.08.009 25173093

17. Meeker JD, Rossano MG, Protas B, Padmanahban V, Diamond MP, Puscheck E,et al. Environmental exposure to metals and male reproductive hormones: circulating testosterone is inversely associated with blood molybdenum. FertilSteril. 2010; 93(1): 130–140.

18. Menke A, Guallar E, Shiels MS, Rohrmann S, Basaria S, 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. doi: 10.1186/1471-2458-8-72 18294394

19. Nagata C, Nagao Y, Shibuya C, Kashiki Y, Shimizu H. Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women.Cancer Epidemiol Biomarkers Prev. 2005; 14(3):705–708. doi: 10.1158/1055-9965.EPI-04-0619 15767353

20. Telisman S., Cvitkovic P., Jurasovic J., Pizent A., Gavella M., Rocic B. Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ. Health Perspect. 2000; 108(1):45–53. doi: 10.1289/ehp.0010845 10620523

21. Kresovich J. K., Argos M. & Turyk M. E. Associations of lead and cadmium with sex hormones in adult males. Environ. Res. 2015;142: 25–33. doi: 10.1016/j.envres.2015.05.026 26093239

22. Telisman S., Colak B., Pizent A., Jurasovic J. & Cvitkovic P. Reproductive toxicity of low-level lead exposure in men. Environ. Res. 2007;105(2):256–266. doi: 10.1016/j.envres.2007.05.011 17632096

23. Chen C, Wang N, Zhai H, Nie X, Sun H, Han B, et al. Associations of blood lead levels with reproductive hormone levels in men and postmenopausal women: Results from the SPECT-China Study. Sci Rep. 2016; 6: 37809. doi: 10.1038/srep37809 27898110

24. Barregård L, Lindstedt G, Schütz A, Sällsten G. Endocrine function in mercury exposed chloralkali workers. Occup Environ Med. 1994;51(8):536–540. doi: 10.1136/oem.51.8.536 7951778

25. Lee B, Pine M, Johnson L, Rettori V, Hiney JK, Dees WL. Manganese acts centrally to activate reproductive hormone secretion and pubertal development in male rats. ReprodToxicol. 2006;22(4):580–585.

26. Adedara IA, Subair TI, Ego VC, Oyediran O, Farombi EO. Chemoprotective role of quercetin in manganese-induced toxicity along the brain-pituitary-testicular axis in rats. Chem Biol Interact. 2017;263:88–98. doi: 10.1016/j.cbi.2016.12.019 28040552

27. Mohammed AT, Ebraheim LLM, Metwally MMM. Ebselen can Protect Male Reproductive Organs and Male Fertility from Manganese Toxicity: Structural and Bioanalytical Approach in a Rat Model. Biomed Pharmacother. 2018;102:739–748. doi: 10.1016/j.biopha.2018.03.086 29604593

28. Liu L, He Y, Xiao Z, Tao W, Zhu J, Wang B, et al. Effects of Selenium Nanoparticles on Reproductive Performance of Male Sprague-Dawley Rats at Supranutritional and Nonlethal Levels. Biol Trace Elem Res. 2017; 180(1):81–89. doi: 10.1007/s12011-017-0980-8 28261763

29. He Y, Chen S, Liu Z, Cheng C, Li H, Wang M. Toxicity of selenium nanoparticles in male Sprague-Dawley rats at supranutritional and nonlethal levels. Life Sci. 2014; 115(1–2):44–51. doi: 10.1016/j.lfs.2014.08.023 25219884

30. Scinicariello F, Buser MC. Serum Testosterone Concentrations and Urinary Bisphenol A, Benzophenone-3, Triclosan, and Paraben Levels in Male and Female Children and Adolescents: NHANES 2011–2012. Environ Health Perspect. 2016; 124(12):1898–1904. doi: 10.1289/EHP150 27383665

31. de Ronde W, van der Schouw YT, Pols HA, Gooren LJ, Muller M, Grobbee DE, et al. Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem. 2006;52(9):1777–1784. doi: 10.1373/clinchem.2005.063354 16793931

32. P, Pandya C, Bhatt N, Gupta SS. Biochemical and reproductive effects of gestational/lactational exposure to lead and cadmium with respect to testicular steroidogenesis, antioxidant system, endogenous sex steroid and cauda-epididymal functions. Andrologia. 2012; 44(2):92–101. doi: 10.1111/j.1439-0272.2010.01109.x 21933222

33. Thoreux-Manlay A, Le Goascogne C, Segretain D, Jégou B, Pinon-Lataillade G. Lead affects steroidogenesis in rat Leydig cells in vivo and in vitro. Toxicology. 1995; 103(1):53–62. doi: 10.1016/0300-483x(95)03107-q 8525490

34. Cupertino MC, Novaes RD, Santos EC, Neves AC, Silva E, Oliveira JA, et al. Differential Susceptibility of Germ and Leydig Cells to Cadmium-Mediated Toxicity: Impact on Testis Structure, Adiponectin Levels, and Steroidogenesis. Oxid Med Cell Longev. 2017;2017:3405089. doi: 10.1155/2017/3405089 29422988

35. Laskey JW, Phelps PV. Effect of cadmium and other metal cations on in vitro Leydig cell testosterone production. Toxicol Appl Pharmacol. 1991; 108(2):296–306. doi: 10.1016/0041-008x(91)90119-y 1850171

36. Zhang Q, Zou P, Zhan H, Zhang M, Zhang L, Ge RS, Huang Y. Dihydrolipoamide dehydrogenase and cAMP are associated with cadmium-mediated Leydig cell damage. Toxicol Lett. 2011; 205(2):183–189. doi: 10.1016/j.toxlet.2011.06.003 21699967

37. Lafuente A, Márquez N, Pérez-Lorenzo M, Pazo D, Esquifino AI. Pubertal and postpubertal cadmium exposure differentially affects the hypothalamic-pituitary-testicular axis function in the rat. Food Chem Toxicol. 2000; 38(10):913–923. doi: 10.1016/s0278-6915(00)00077-6 11039325

38. Ronis MJ, Badger TM, Shema SJ, Roberson PK, Shaikh F. Reproductive toxicity and growth effects in rats exposed to lead at different periods during development. Toxicol Appl Pharmacol. 1996;136(2):361–371. doi: 10.1006/taap.1996.0044 8619245

39. Lafuente A, Márquez N, Pérez-Lorenzo M, Pazo D, Esquifino AI. Cadmium effects on hypothalamic-pituitary-testicular axis in male rats. Exp Biol Med (Maywood). 2001; 226(6):605–611.

40. Gandhi J, Hernandez RJ, Chen A, Smith NL, Sheynkin YR, Joshi G, et al. Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning. Zygote. 2017; 25(2):103–110. doi: 10.1017/S0967199417000028 28185602

41. Das S, Mukherjee D. Effect of cadmium chloride on secretion of 17β-estradiol by the ovarian follicles of common carp, Cyprinus carpio. Gen Comp Endocrinol. 2013; 181: 107–114. doi: 10.1016/j.ygcen.2012.10.010 23146792

42. Davis J, Khan G, Martin MB, Hilakivi-Clarke L. Effects of maternal dietary exposure to cadmium during pregnancy on mammary cancer risk among female offspring.J Carcinog. 2013; 12:11. doi: 10.4103/1477-3163.114219 23858299

43. Dees WL, Hiney JK, Srivastava VK. Influences of manganese on pubertal development. J Endocrinol. 2017; 235(1): R33–R42. doi: 10.1530/JOE-17-0237 28720645

44. Zheng W, Kim H, Zhao Q. Comparative toxicokinetics of manganese chloride and methylcyclopentadienyl manganese tricarbonyl (MMT) in Sprague-Dawley rats. Toxicol Sci. 2000; 54(2): 295–301. doi: 10.1093/toxsci/54.2.295 10774811

45. Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, et al. Dual function of the selenoproteinPHGPx during sperm maturation. Science. 1999; 285(5432): 1393–1396. doi: 10.1126/science.285.5432.1393 10464096

46. Shi L, Song R, Yao X, Ren Y. Effects of selenium on the proliferation, apoptosis and testosterone production of sheep Leydig cells in vitro. Theriogenology. 2017; 93: 24–32. doi: 10.1016/j.theriogenology.2017.01.022 28257863

47. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009; 181(2): 741–751. doi: 10.1016/j.juro.2008.10.015 19091331

Článek vyšel v časopise


2019 Číslo 11