Ann Pediatr Endocrinol Metab.  2019 Jun;24(2):78-91. 10.6065/apem.2019.24.2.78.

Early-life exposure to endocrine-disrupting chemicals and pubertal development in girls

• Lee JE
• Jung HW
• Lee YJ
• Lee YA

• KMID: 2452083
• DOI: http://doi.org/10.6065/apem.2019.24.2.78

Abstract

Over the last decades, the onset of puberty in girls has occurred earlier, but the tempo of pubertal progression has been relatively slower, resulting in a younger age at puberty onset without a change in age at menarche. Sufficient energy availability and adiposity contribute to early pubertal development, and environmental factors, such as endocrine-disrupting chemicals (EDCs), may affect not only the control of energy balance, but also puberty and reproduction. EDCs are hormonally active substances that can perturb puberty by acting both peripherally on target organs, such as adipose tissue or adrenal glands, and/or centrally on the hypothalamic-pituitary-gonadal (HPG) axis. Depending on whether the exposure takes place earlier during fetal and neonatal life or later during early childhood, EDCs can lead to different outcomes through different mechanisms. Evidence of associations between exposures to EDCs and altered pubertal timing makes it reasonable to support their relationship. However, human epidemiologic data are limited or inconsistent and cannot provide sufficient evidence for a causal relationship between EDC exposure and changes in pubertal timing. Further investigation is warranted to determine the overall or different effects of EDCs exposure during prenatal or childhood windows on pubertal milestones and to reveal the underlying mechanisms, including epigenetic marks, whereby early-life exposure to EDCs affect the HPG-peripheral tissue axis.

Keyword

Puberty; Endocrine disrupting chemicals; Secular trend

MeSH Terms

Adipose Tissue
Adiposity
Adolescent
Adrenal Glands
Endocrine Disruptors
Epigenomics
Female*
Humans
Menarche
Puberty
Reproduction
Endocrine Disruptors

Reference

References

1. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016; 4:254–64.

2. Parent AS, Franssen D, Fudvoye J, Gérard A, Bourguignon JP. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents. Front Neuroendocrinol. 2015; 38:12–36.

3. hn JH, Lim SW, Song BS, Seo J, Lee JA, Kim DH, et al. Age at menarche in the Korean female: secular trends and relationship to adulthood body mass index. Ann Pediatr Endocrinol Metab. 2013; 18:60–4.

4. Cho GJ, Park HT, Shin JH, Hur JY, Kim YT, Kim SH, et al. Age at menarche in a Korean population: secular trends and influencing factors. Eur J Pediatr. 2010; 169:89–94.

5. Aksglaede L, Sørensen K, Petersen JH, Skakkebaek NE, Juul A. Recent decline in age at breast development: the Copenhagen Puberty Study. Pediatrics. 2009; 123:e932–9.

6. Zhu J, Kusa TO, Chan YM. Genetics of pubertal timing. Curr Opin Pediatr. 2018; 30:532–40.

7. Biro FM, Khoury P, Morrison JA. Influence of obesity on timing of puberty. Int J Androl. 2006; 29:272–7. ; discussion 286-90.

8. Cheng G, Buyken AE, Shi L, Karaolis-Danckert N, Kroke A, Wudy SA, et al. Beyond overweight: nutrition as an important lifestyle factor influencing timing of puberty. Nutr Rev. 2012; 70:133–52.

9. Dunger DB, Ahmed ML, Ong KK. Early and late weight gain and the timing of puberty. Mol Cell Endocrinol. 2006; 254-255:140–5.

10. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev. 2015; 36:E1–E150.

11. Frisch RE, Revelle R. Height and weight at menarche and a hypothesis of critical body weights and adolescent events. Science. 1970; 169:397–9.

12. Elks CE, Perry JR, Sulem P, Chasman DI, Franceschini N, He C, et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat Genet. 2010; 42:1077–85.

13. Perry JR, Day F, Elks CE, Sulem P, Thompson DJ, Ferreira T, et al. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature. 2014; 514:92–7.

14. Willemsen RH, Dunger DB. Normal variation in pubertal timing: genetic determinants in relation to growth and adiposity. Endocr Dev. 2016; 29:17–35.

15. Roth CL, DiVall S. Consequences of early life programing by genetic and environmental influences: a synthesis regarding pubertal Timing. Endocr Dev. 2016; 29:134–52.

16. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001; 108:347–53.

17. Shalitin S, Kiess W. Putative Effects of Obesity on Linear Growth and Puberty. Horm Res Paediatr. 2017; 88:101–10.

18. Lomniczi A, Loche A, Castellano JM, Ronnekleiv OK, Bosch M, Kaidar G, et al. Epigenetic control of female puberty. Nat Neurosci. 2013; 16:281–9.

19. Vazquez MJ, Toro CA, Castellano JM, Ruiz-Pino F, Roa J, Beiroa D, et al. SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression. Nat Commun. 2018; 9:4194.

20. Parent AS, Franssen D, Fudvoye J, Pinson A, Bourguignon JP. Current changes in pubertal timing: revised vision in relation with environmental factors including endocrine disruptors. Endocr Dev. 2016; 29:174–84.

21. Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev. 2003; 24:668–93.

22. Euling SY, Selevan SG, Pescovitz OH, Skakkebaek NE. Role of environmental factors in the timing of puberty. Pediatrics. 2008; 121 Suppl 3:S167–71. pii: E5. https://doi.org/10.3390/toxics7010005.

23. Combarnous Y, Nguyen TMD. Comparative overview of the mechanisms of action of hormones and endocrine disruptor compounds. Toxics. 2019; 7.

24. Bourguignon JP, Juul A, Franssen D, Fudvoye J, Pinson A, Parent AS. Contribution of the endocrine perspective in the evaluation of endocrine disrupting chemical effects: the case study of pubertal timing. Horm Res Paediatr. 2016; 86:221–32.

25. Mouritsen A, Aksglaede L, Sørensen K, Mogensen SS, Leffers H, Main KM, et al. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. Int J Androl. 2010; 33:346–59.

26. Greenspan LC, Lee MM. Endocrine disrupters and pubertal timing. Curr Opin Endocrinol Diabetes Obes. 2018; 25(1):49–54.

27. Völkel W, Colnot T, Csanády GA, Filser JG, Dekant W. Metabolism and kinetics of bisphenol a in humans at low doses following oral administration. Chem Res Toxicol. 2002; 15:1281–7.

28. Wetherill YB, Akingbemi BT, Kanno J, McLachlan JA, Nadal A, Sonnenschein C, et al. In vitro molecular mechanisms of bisphenol A action. Reprod Toxicol. 2007; 24:178–98.

29. Han EJ, Yim OK, Chung J, Baek SY, Kim Y. The study of relationship between the concentrations of Bisphenol A and DEHP in human plasma and precocious puberty. Anal Sci Technol. 2008; 21:375–82.

30. Wolff MS, Britton JA, Boguski L, Hochman S, Maloney N, Serra N, et al. Environmental exposures and puberty in inner-city girls. Environ Res. 2008; 107:393–400.

31. Lee SW, Lee WJ, Chae HW, Lee EB, Kim JH, Kim DH, et al. Determination of serum Di-(2-ethylhexyl) phthalate and bisphenol A level in children with idiopathic central precocious puberty. J Korean Soc Pediatr Endocrinol. 2009; 14:154–62.

32. Qiao L, Zheng L, Cai D. Study on the levels of the bisphenol A, octylphenol, 4-nonylphenol in serum of precocious girls. Wei Sheng Yan Jiu. 2010; 39:9–12.

33. Wolff MS, Teitelbaum SL, Pinney SM, Windham G, Liao L, Biro F, et al. Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. Environ Health Perspect. 2010; 118:1039–46.

34. Buttke DE, Sircar K, Martin C. Exposures to endocrine-disrupting chemicals and age of menarche in adolescent girls in NHANES (2003-2008). Environ Health Perspect. 2012; 120:1613–8.

35. Frederiksen H, Aksglaede L, Sorensen K, Nielsen O, Main KM, Skakkebaek NE, et al. Bisphenol A and other phenols in urine from Danish children and adolescents analyzed by isotope diluted TurboFlow-LC-MS/MS. Int J Hyg Environ Health. 2013; 216:710–20.

36. Yum T, Lee S, Kim Y. Association between precocious puberty and some endocrine disruptors in human plasma. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2013; 48:912–7.

37. Durmaz E, Aşçı A, Erkekoğlu P, Akçurin S, Gümüşel BK, Bircan I. Urinary bisphenol a levels in girls with idiopathic central precocious puberty. J Clin Res Pediatr Endocrinol. 2014; 6:16–21.

38. Lee SH, Kang SM, Choi MH, Lee J, Park MJ, Kim SH, et al. Changes in steroid metabolism among girls with precocious puberty may not be associated with urinary levels of bisphenol A. Reprod Toxicol. 2014; 44:1–6.

39. Chen LH, Shi JR, Fang YL, Liang L, Chen WQ, Chen XZ. Serum bisphenol A concentration and premature thelarche in female infants aged 4-month to 2-year. Indian J Pediatr. 2015; 82:221–4.

40. McGuinn LA, Ghazarian AA, Joseph Su L, Ellison GL. Urinary bisphenol A and age at menarche among adolescent girls: evidence from NHANES 2003-2010. Environ Res. 2015; 136:381–6.

41. Wolff MS, Teitelbaum SL, McGovern K, Pinney SM, Windham GC, Galvez M, et al. Environmental phenols and pubertal development in girls. Environ Int. 2015; 84:174–80.

42. Buluş AD, Aşci A, Erkekoglu P, Balci A, Andiran N, Koçer-Gümüşel B. The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty. Toxicol Mech Methods. 2016; 26:493–500.

43. Özgen İT, Torun E, Bayraktar-Tanyeri B, Durmaz E, Kılıç E, Cesur Y. The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche. J Pediatr Endocrinol Metab. 2016; 29:337–41.

44. Supornsilchai V, Jantarat C, Nosoognoen W, Pornkunwilai S, Wacharasindhu S, Soder O. Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty. J Pediatr Endocrinol Metab. 2016; 29:1233–9.

45. Kasper-Sonnenberg M, Wittsiepe J, Wald K, Koch HM, Wilhelm M. Pre-pubertal exposure with phthalates and bisphenol A and pubertal development. PLoS One. 2017; 12:e0187922.

46. Miao M, Wang Z, Liu X, Liang H, Zhou Z, Tan H, et al. Urinary bisphenol A and pubertal development in Chinese school-aged girls: a cross-sectional study. Environ Health. 2017; 16:80.

47. Wolff MS, Pajak A, Pinney SM, Windham GC, Galvez M, Rybak M, et al. Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls. Reprod Toxicol. 2017; 67:56–64.

48. Watkins DJ, Sánchez BN, Téllez-Rojo MM, Lee JM, Mercado-García A, Blank-Goldenberg C, et al. Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls. Environ Res. 2017; 159:143–51.

49. Berger K, Eskenazi B, Kogut K, Parra K, Lustig RH, Greenspan LC, et al. Association of prenatal urinary concentrations of phthalates and bisphenol A and pubertal timing in boys and girls. Environ Health Perspect. 2018; 126:97004.

50. Chen Y, Wang Y, Ding G, Tian Y, Zhou Z, Wang X, et al. Association between bisphenol a exposure and idiopathic central precocious puberty (ICPP) among school-aged girls in Shanghai, China. Environ Int. 2018; 115:410–6.

51. Durmaz E, Asci A, Erkekoglu P, Balcı A, Bircan I, Koçer-Gumusel B. Urinary bisphenol A levels in Turkish girls with premature thelarche. Hum Exp Toxicol. 2018; 37:1007–16.

52. Leonardi A, Cofini M, Rigante D, Lucchetti L, Cipolla C, Penta L, et al. The effect of bisphenol A on puberty: a critical review of the medical literature. Int J Environ Res Public Health. 2017; 14.

53. Benjamin S, Masai E, Kamimura N, Takahashi K, Anderson RC, Faisal PA. Phthalates impact human health: epidemiological evidences and plausible mechanism of action. J Hazard Mater. 2017; 340:360–83.

54. Colón I, Caro D, Bourdony CJ, Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect. 2000; 108:895–900.

55. Qiao L, Zheng L, Cai D. Study on the di-n-butyl phthalate and di-2-ethylhexyl phthalate level of girl serum related with precocious puberty in Shanghai. Wei Sheng Yan Jiu. 2007; 36:93–5.

56. Chou YY, Huang PC, Lee CC, Wu MH, Lin SJ. Phthalate exposure in girls during early puberty. J Pediatr Endocrinol Metab. 2009; 22:69–77.

57. Frederiksen H, Sørensen K, Mouritsen A, Aksglaede L, Hagen CP, Petersen JH, et al. High urinary phthalate concentration associated with delayed pubarche in girls. Int J Androl. 2012; 35:216–26.

58. Chen CY, Chou YY, Wu YM, Lin CC, Lin SJ, Lee CC. Phthalates may promote female puberty by increasing kisspeptin activity. Hum Reprod. 2013; 28:2765–73.

59. Mouritsen A, Frederiksen H, Sørensen K, Aksglaede L, Hagen C, Skakkebaek NE, et al. Urinary phthalates from 168 girls and boys measured twice a year during a 5-year period: associations with adrenal androgen levels and puberty. J Clin Endocrinol Metab. 2013; 98:3755–64.

60. Wolff MS, Teitelbaum SL, McGovern K, Windham GC, Pinney SM, Galvez M, et al. Phthalate exposure and pubertal development in a longitudinal study of US girls. Hum Reprod. 2014; 29:1558–66.

61. Zhang Y, Cao Y, Shi H, Jiang X, Zhao Y, Fang X, et al. Could exposure to phthalates speed up or delay pubertal onset and development? A 1.5-year follow-up of a school-based population. Environ Int. 2015; 83:41–9.

62. Srilanchakon K, Thadsri T, Jantarat C, Thengyai S, Nosoognoen W, Supornsilchai V. Higher phthalate concentrations are associated with precocious puberty in normal weight Thai girls. J Pediatr Endocrinol Metab. 2017; 30:1293–8.

63. Binder AM, Corvalan C, Calafat AM, Ye X, Mericq V, Pereira A, et al. Childhood and adolescent phenol and phthalate exposure and the age of menarche in Latina girls. Environ Health. 2018; 17:32.

64. Durmaz E, Erkekoglu P, Asci A, Akçurin S, Bircan İ, Kocer-Gumusel B. Urinary phthalate metabolite concentrations in girls with premature thelarche. Environ Toxicol Pharmacol. 2018; 59:172–81.

65. Hashemipour M, Kelishadi R, Amin MM, Ebrahim K. Is there any association between phthalate exposure and precocious puberty in girls? Environ Sci Pollut Res Int. 2018; 25:13589–96.

66. Mnif W, Hassine AI, Bouaziz A, Bartegi A, Thomas O, Roig B. Effect of endocrine disruptor pesticides: a review. Int J Environ Res Public Health. 2011; 8:2265–303.

67. Crellin NK, Rodway MR, Swan CL, Gillio-Meina C, Chedrese PJ. Dichlorodiphenyldichloroethylene potentiates the effect of protein kinase A pathway activators on progesterone synthesis in cultured porcine granulosa cells. Biol Reprod. 1999; 61:1099–103.

68. Tsai WT. Current status and regulatory aspects of pesticides considered to be persistent organic pollutants (POPs) in Taiwan. Int J Environ Res Public Health. 2010; 7:3615–27.

69. Turusov V, Rakitsky V, Tomatis L. Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks. Environ Health Perspect. 2002; 110:125–8.

70. Vasiliu O, Muttineni J, Karmaus W. In utero exposure to organochlorines and age at menarche. Hum Reprod. 2004; 19:1506–12.

71. Ouyang F, Perry MJ, Venners SA, Chen C, Wang B, Yang F, et al. Serum DDT, age at menarche, and abnormal menstrual cycle length. Occup Environ Med. 2005; 62:878–84.

72. Denham M, Schell LM, Deane G, Gallo MV, Ravenscroft J, DeCaprio AP, et al. Relationship of lead, mercury, mirex, di chlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls. Pediatrics. 2005; 115:e127–34.

73. Den Hond E, Dhooge W, Bruckers L, Schoeters G, Nelen V, van de Mieroop E, et al. Internal exposure to pollutants and sexual maturation in Flemish adolescents. J Expo Sci Environ Epidemiol. 2011; 21:224–33.

74. Deng F, Tao FB, Liu DY, Xu YY, Hao JH, Sun Y, et al. Effects of growth environments and two environmental endocrine disruptors on children with idiopathic precocious puberty. Eur J Endocrinol. 2012; 166:803–9.

75. Ozen S, Darcan S, Bayindir P, Karasulu E, Simsek DG, Gurler T. Effects of pesticides used in agriculture on the development of precocious puberty. Environ Monit Assess. 2012; 184:4223–32.

76. Windham GC, Pinney SM, Voss RW, Sjödin A, Biro FM, Greenspan LC, et al. Brominated flame retardants and other persistent organohalogenated compounds in relation to timing of puberty in a longitudinal study of girls. Environ Health Perspect. 2015; 123:1046–52.

77. Bapayeva G, Issayeva R, Zhumadilova A, Nurkasimova R, Kulbayeva S, Tleuzhan R. Organochlorine pesticides and female puberty in South Kazakhstan. Reprod Toxicol. 2016; 65:67–75.

78. Namulanda G, Maisonet M, Taylor E, Flanders WD, Olson D, Sjodin A, et al. In utero exposure to organochlorine pesticides and early menarche in the Avon Longitudinal Study of Parents and Children. Environ Int. 2016; 94:467–72.

79. Morgan MK, MacMillan DK, Zehr D, Sobus JR. Pyrethroid insecticides and their environmental degradates in repeated duplicate-diet solid food samples of 50 adults. J Expo Sci Environ Epidemiol. 2018; 28:40–5.

80. Burns CJ, Pastoor TP. Pyrethroid epidemiology: a quality-based review. Crit Rev Toxicol. 2018; 48:297–311.

81. Ye X, Pan W, Zhao Y, Zhao S, Zhu Y, Liu W, et al. Association of pyrethroids exposure with onset of puberty in Chinese girls. Environ Pollut. 2017; 227:606–12.

82. Schecter A, Birnbaum L, Ryan JJ, Constable JD. Dioxins: an overview. Environ Res. 2006; 101:419–28.

83. Carpenter DO. Polychlorinated biphenyls (PCBs): routes of exposure and effects on human health. Rev Environ Health. 2006; 21:1–23.

84. Ritter R, Scheringer M, MacLeod M, Moeckel C, Jones KC, Hungerbühler K. Intrinsic human elimination half-lives of polychlorinated biphenyls derived from the temporal evolution of cross-sectional biomonitoring data from the United Kingdom. Environ Health Perspect. 2011; 119:225–31.

85. Den Hond E, Roels HA, Hoppenbrouwers K, Nawrot T, Thijs L, Vandermeulen C, et al. Sexual maturation in relation to polychlorinated aromatic hydrocarbons: Sharpe and Skakkebaek's hypothesis revisited. Environ Health Perspect. 2002; 110:771–6.

86. Warner M, Samuels S, Mocarelli P, Gerthoux PM, Needham L, Patterson DG Jr, et al. Serum dioxin concentrations and age at menarche. Environ Health Perspect. 2004; 112:1289–92.

87. Leijs MM, Koppe JG, Olie K, van Aalderen WM, Voogt Pd, Vulsma T, et al. Delayed initiation of breast development in girls with higher prenatal dioxin exposure; a longitudinal cohort study. Chemosphere. 2008; 73:999–1004.

88. Sjödin A, Patterson DG Jr, Bergman A. A review on human exposure to brominated flame retardants--particularly polybrominated diphenyl ethers. Environ Int. 2003; 29:829–39.

89. Yang W, Mu Y, Giesy JP, Zhang A, Yu H. Anti-androgen activity of polybrominated diphenyl ethers determined by comparative molecular similarity indices and molecular docking. Chemosphere. 2009; 75:1159–64.

90. Blanck HM, Marcus M, Tolbert PE, Rubin C, Henderson AK, Hertzberg VS, et al. Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology. 2000; 11:641–7.

91. Chen A, Chung E, DeFranco EA, Pinney SM, Dietrich KN. Serum PBDEs and age at menarche in adolescent girls: analysis of the National Health and Nutrition Examination Survey 2003-2004. Environ Res. 2011; 111:831–7.

92. Deodati A, Sallemi A, Maranghi F, Germani D, Puglianiello A, Baldari F, et al. Serum levels of polybrominated diphenyl ethers in girls with premature thelarche. Horm Res Paediatr. 2016; 86:233–9.

93. Harley KG, Rauch SA, Chevrier J, Kogut K, Parra KL, Trujillo C, et al. Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls. Environ Int. 2017; 100:132–8.