Environmental Monitoring and Assessment

, Volume 184, Issue 7, pp 4223–4232 | Cite as

Effects of pesticides used in agriculture on the development of precocious puberty

  • Samim OzenEmail author
  • Sukran Darcan
  • Petek Bayindir
  • Ercument Karasulu
  • Damla Goksen Simsek
  • Tahir Gurler


The present study aims to evaluate the effects of pesticides on premature breast development. Forty-five girls (group 1) with premature breast development living in the Menderes region, where greenhouse cultivation is the main income, 16 girls (group 2) living in Izmir city with early puberty, and 33 girls (group 3) who had no signs of puberty were included in the study. Endosulphan 1, endosulphan 2, endosulphan sulphate, methoxychlor, vinclozolin, 4,4-dichlorodiphenyldichlorethylene (DDE), 4,-dichlorodiphenyltrichloroethane (DDT), and 2,4-DDT were evaluated in the serum and adipose tissues of the groups by using a gas chromatography–mass spectrometry method. With the exception of 4,4′-DDE, the pesticides studied were undetectable in the serum and adipose tissue samples. The levels of basal luteinizing hormone (LH), stimulated LH, follicle-stimulating hormone, and the long axis of the uterus and both ovaries were significantly different in the girls who had premature thelarche and detectable 4,4′-DDE levels compared to the girls who had premature thelarche and undetectable 4,4′-DDE levels in serum and adipose tissues. The presence and levels of pesticides in serum and adipose tissues were not related to precocious puberty (PP). The mechanisms that lead to PP may also result in obesity, and obesity may be the underlying cause for PP in this group.


Precocious puberty Environmental endocrine disruptors Pesticides 



This study was supported by the Ege University Research Committee.

Conflict of interest

The authors declare there is no conflict of interest in this paper.


  1. Abaci, A., Demir, K., Bober, E., & Buyukgebiz, A. (2009). Endocrine disrupters—with special emphasis on sexual development. Pediatric Endocrinology Reviews, 6, 464–475.Google Scholar
  2. Anderson, S. E., & Must, A. (2005). Interpreting the continued decline in the average age at menarche: results from two nationally representative surveys of U.S. girls studied 10 years apart. The Journal of Pediatrics, 147, 753–760.CrossRefGoogle Scholar
  3. Badouraki, M., Christoforidis, A., Economou, I., Dimitriadis, A. S., & Katzos, G. (2008). Evaluation of pelvic ultrasonography in the diagnosis and differentiation of various forms of sexual precocity in girls. Ultrasound in Obstetrics & Gynecology, 32, 819–827.CrossRefGoogle Scholar
  4. Blanck, H. M., Marcus, M., Hertzberg, V., Tolbert, P. E., Rubin, C., Henderson, A. K., et al. (2000). Determinants of polybrominated biphenyl serum decay among women in the Michigan PBB cohort. Environmental Health Perspectives, 108, 147–152.CrossRefGoogle Scholar
  5. Blanck, H. M., Marcus, M., Tolbert, P. E., Rubin, C., Henderson, A. K., Hertzberg, V. S., et al. (2000). Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology, 11, 641–647.CrossRefGoogle Scholar
  6. Blystone, C. R., Lambright, C. S., Cardon, M. C., Furr, J., Rider, C. V., Hartig, P. C., et al. (2009). Cumulative and antagonistic effects of a mixture of the antiandrogens vinclozolin and iprodione in the pubertal male rat. Toxicological Sciences, 111, 179–188.CrossRefGoogle Scholar
  7. Buck Louis, G. M., Gray, L. E., Jr., Marcus, M., Ojeda, S. R., Pescovitz, O. H., Witchel, S. F., et al. (2008). Environmental factors and puberty timing: expert panel research needs. Pediatrics, 121, S192–S207.CrossRefGoogle Scholar
  8. Carel, J. C., & Léger, J. (2008). Clinical practice. Precocious puberty. The New England Journal of Medicine, 358, 2366–2377.CrossRefGoogle Scholar
  9. Cavallo, A., & Zhou, X. H. (1994). LHRH test in the assessment of puberty in normal children. Hormone Research, 41, 10–15.CrossRefGoogle Scholar
  10. Cavallo, A., Richards, G. E., Busey, S., & Michaels, S. E. (1995). A simplified gonadotrophin-releasing hormone test for precocious puberty. Clinical Endocrinology (Oxf), 42, 641–646.CrossRefGoogle Scholar
  11. Codner, E., & Román, R. (2008). Premature thelarche from phenotype to genotype. Pediatric Endocrinology Reviews, 5, 760–765.Google Scholar
  12. Cok, I., Bilgili, A., Yarsan, E., Bagci, C., & Burgaz, S. (1998). Organochlorine pesticide residue levels in human adipose tissue of residents of Manisa (Turkey), 1995–1996. Bulletin of Environmental Contamination and Toxicology, 61, 311–316.CrossRefGoogle Scholar
  13. Colón, I., Caro, D., Bourdony, C. J., & Rosario, O. (2000). Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environmental Health Perspectives, 108, 895–900.CrossRefGoogle Scholar
  14. Cooper, R. L., & Kavlock, R. J. (1997). Endocrine disruptors and reproductive development: a weight-of-evidence overview. The Journal of Endocrinology, 152, 159–166.CrossRefGoogle Scholar
  15. Dattani, M., & Hindmarsh, P. (2005). Normal and abnormal puberty. In C. Brook, P. Clayton, & R. Brown (Eds.), Brook’s clinical pediatric endocrinology (pp. 182–210). Massachusetts: Blackwell Publishing.Google Scholar
  16. de Vries, L., Horev, G., Schwartz, M., & Phillip, M. (2006). Ultrasonographic and clinical parameters for early differentiation between precocious puberty and premature thelarche. European Journal of Endocrinology, 154, 891–898.CrossRefGoogle Scholar
  17. Den Hond, E., & Schoeters, G. (2006). Endocrine disrupters and human puberty. International Journal of Andrology, 29, 264–290.CrossRefGoogle Scholar
  18. Denham, M., Schell, L. M., Deane, G., Gallo, M. V., Ravenscroft, J., DeCaprio, A. P., et al. (2005). Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls. Pediatrics, 115, e127–e134.CrossRefGoogle Scholar
  19. Diamanti-Kandarakis, E., Bourguignon, J. P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., et al. (2009). Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocrine Reviews, 30, 293–342.CrossRefGoogle Scholar
  20. Fenton, S. E. (2006). Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. Endocrinology, 147, S18–S24.CrossRefGoogle Scholar
  21. Gladen, B. C., Ragan, N. B., & Rogan, W. J. (2000). Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. The Journal of Pediatrics, 136, 490–496.CrossRefGoogle Scholar
  22. Golub, M. S., Hogrefe, C. E., Germann, S. L., Lasley, B. L., Natarajan, K., & Tarantal, A. F. (2003). Effects of exogenous estrogenic agents on pubertal growth and reproductive system maturation in female rhesus monkeys. Toxicological Sciences, 74, 103–113.CrossRefGoogle Scholar
  23. Gray, L. E., Jr., Ostby, J., Ferrell, J., Rehnberg, G., Linder, R., Cooper, R., et al. (1989). A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fundamental and Applied Toxicology, 12, 92–108.CrossRefGoogle Scholar
  24. Guo, Y. L., Lambert, G. H., Hsu, C. C., & Hsu, M. M. (2004). Yucheng: health effects of prenatal exposure to polychlorinated biphenyls and dibenzofurans. International Archives of Occupational and Environmental Health, 77, 153–158.CrossRefGoogle Scholar
  25. Herman-Giddens, M. E. (2007). Puberty is starting earlier in the 21st century. In O. H. Pescovitz & E. C. Walvoord (Eds.), When puberty is precocious: scientific and clinical aspects (pp. 105–136). Totowa: Humana Press.CrossRefGoogle Scholar
  26. Herter, L. D., Golendziner, E., Flores, J. A., Moretto, M., Di Domenico, K., Becker, E., Jr., et al. (2002). Ovarian and uterine findings in pelvic sonography: comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty. Journal of Ultrasound in Medicine, 21, 1237–1246.Google Scholar
  27. Ikegami, S., Moriwake, T., Tanaka, H., Inoue, M., Kubo, T., Suzuki, S., et al. (2001). An ultrasensitive assay revealed age-related changes in serum oestradiol at low concentrations in both sexes from infancy to puberty. Clinical Endocrinology (Oxf), 55, 789–795.CrossRefGoogle Scholar
  28. Jacobson-Dickman, E., & Lee, M. M. (2009). The influence of endocrine disruptors on pubertal timing. Current Opinion in Endocrinology, Diabetes, and Obesity, 16, 25–30.CrossRefGoogle Scholar
  29. Kaplowitz, P. (2007). BMI and onset of puberty. In O. H. Pescovitz & E. C. Walvoord (Eds.), When puberty is precocious: scientific and clinical aspects (p. 137). New Jersey: Humana Press.CrossRefGoogle Scholar
  30. Kaplowitz, P. B., Slora, E. J., Wasserman, R. C., Pedlow, S. E., & Herman-Giddens, M. E. (2001). Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics, 108, 347–353.CrossRefGoogle Scholar
  31. Karlberg, J. (2002). Secular trends in pubertal development. Hormone Research, 57, 19–30.CrossRefGoogle Scholar
  32. Khurana, S., Ranmal, S., & Ben-Jonathan, N. (2000). Exposure of newborn male and female rats to environmental estrogens: delayed and sustained hyperprolactinemia and alterations in estrogen receptor expression. Endocrinology, 141, 4512–4517.CrossRefGoogle Scholar
  33. Klein, K. O., Mericq, V., Brown-Dawson, J. M., Larmore, K. A., Cabezas, P., & Cortinez, A. (1999). Estrogen levels in girls with premature thelarche compared with normal prepubertal girls as determined by an ultrasensitive recombinant cell bioassay. The Journal of Pediatrics, 134, 190–192.CrossRefGoogle Scholar
  34. Krstevska-Konstantinova, M., Charlier, C., Craen, M., Du Caju, M., Heinrichs, C., de Beaufort, C., et al. (2001). Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticides. Human Reproduction, 16, 1020–1026.CrossRefGoogle Scholar
  35. Lee, P. A., & Houk, C. P. (2007). Puberty and its disorders. In F. Lifshitz (Ed.), Pediatric endocrinology (pp. 273–303). New York: Informa Healthcare.Google Scholar
  36. Markey, C. M., Luque, E. H., Munoz De Toro, M., Sonnenschein, C., & Soto, A. M. (2001). In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biology of Reproduction, 65, 1215–1223.Google Scholar
  37. Marshall, W. A., & Tanner, J. M. (1969). Variations in pattern of pubertal changes in girls. Archives of Disease in Childhood, 44, 291–303.CrossRefGoogle Scholar
  38. Marty, M. S., Crissman, J. W., & Carney, E. W. (1999). Evaluation of the EDSTAC female pubertal assay in CD rats using 17beta-estradiol, steroid biosynthesis inhibitors, and a thyroid inhibitor. Toxicological Sciences, 52, 269–277.CrossRefGoogle Scholar
  39. Massart, F., Parrino, R., Seppia, P., Federico, G., & Saggese, G. (2006). How do environmental estrogen disruptors induce precocious puberty? Minerva Pediatrica, 58, 247–254.Google Scholar
  40. Masutomi, N., Shibutani, M., Takagi, H., Uneyama, C., Takahashi, N., & Hirose, M. (2003). Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life. Toxicology, 192, 149–170.CrossRefGoogle Scholar
  41. McLachlan, J. A., Simpson, E., & Martin, M. (2006). Endocrine disrupters and female reproductive health. Best Practice & Research. Clinical Endocrinology & Metabolism, 20, 63–75.CrossRefGoogle Scholar
  42. Mul, D., Oostdijk, W., & Drop, S. L. (2002). Early puberty in adopted children. Hormone Research, 57, 1–9.CrossRefGoogle Scholar
  43. Muñoz-de-Toro, M., Markey, C. M., Wadia, P. R., Luque, E. H., Rubin, B. S., Sonnenschein, C., et al. (2005). Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology, 146, 4138–4147.CrossRefGoogle Scholar
  44. Nebesio, T. D., & Pescovitz, O. H. (2007). The role of endocrine disruptors in pubertal development. In O. H. Pescovitz & E. C. Walvoord (Eds.), When puberty is precocious: scientific and clinical aspects (pp. 425–419). New Jersey: Humana Press.CrossRefGoogle Scholar
  45. Neely, E. K., Wilson, D. M., Lee, P. A., Stene, M., & Hintz, R. L. (1995). Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty. The Journal of Pediatrics, 127, 47–52.CrossRefGoogle Scholar
  46. Neyzi, O., Binyıldız, P., & Alp, H. (1978). Türk çocuklarında büyüme-gelişme normları. I. Tartı ve boy değerleri. Ýstanbul Týp Fakültesi Mecmuasý, 41, 74–81.Google Scholar
  47. Ouyang, F., Perry, M. J., Venners, S. A., Chen, C., Wang, B., Yang, F., et al. (2005). Serum DDT, age at menarche, and abnormal menstrual cycle length. Occupational and Environmental Medicine, 62, 878–884.CrossRefGoogle Scholar
  48. Parent, A. S., Teilmann, G., Juul, A., Skakkebaek, N. E., Toppari, J., & Bourguignon, J. P. (2003). The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocrine Reviews, 24, 668–693.CrossRefGoogle Scholar
  49. Pitarch, E., López, F. J., Serrano, R., & Hernández, F. (2001). Multiresidue determination of organophosphorus and organochlorine pesticides in human biological fluids by capillary gas chromatography. Fresenius’ Journal of Analytical Chemistry, 369, 502–509.CrossRefGoogle Scholar
  50. Presibella, K. M., Kita, D. H., Carneiro, C. B., Andrade, A. J., & Dalsenter, P. R. (2005). Reproductive evaluation of two pesticides combined (deltamethrin and endosulfan) in female rats. Reproductive Toxicology, 20, 95–101.CrossRefGoogle Scholar
  51. Resende, E. A., Lara, B. H., Reis, J. D., Ferreira, B. P., Pereira, G. A., & Borges, M. F. (2007). Assessment of basal and gonadotropin-releasing hormone-stimulated gonadotropins by immunochemiluminometric and immunofluorometric assays in normal children. The Journal of Clinical Endocrinology and Metabolism, 92, 1424–1429.CrossRefGoogle Scholar
  52. Rosenfield, R. L., Cooke, D. W., & Radovic, S. (2008). Puberty and its disorders in the female. In M. A. Sperling (Ed.), Pediatric endocrinology (pp. 530–609). Philadelphia: Saunders Elsevier.CrossRefGoogle Scholar
  53. Rosenfield, R. L., Lipton, R. B., & Drum, M. L. (2009). Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index. Pediatrics, 123, 84–88.CrossRefGoogle Scholar
  54. Roy, J. R., Chakraborty, S., & Chakraborty, T. R. (2009). Estrogen-like endocrine disrupting chemicals affecting puberty in humans—a review. Medical Science Monitor, 15, RA137–RA145.Google Scholar
  55. Sagiv, S. K., Tolbert, P. E., Altshul, L. M., & Korrick, S. A. (2007). Organochlorine exposures during pregnancy and infant size at birth. Epidemiology, 18, 120–129.CrossRefGoogle Scholar
  56. Schoeters, G., Den Hond, E., Dhooge, W., van Larebeke, N., & Leijs, M. (2008). Endocrine disruptors and abnormalities of pubertal development. Basic & Clinical Pharmacology & Toxicology, 102, 168–175.CrossRefGoogle Scholar
  57. Stanhope, R. (2000). Premature thelarche: clinical follow-up and indication for treatment. Journal of Pediatric Endocrinology & Metabolism, 13, 827–830.CrossRefGoogle Scholar
  58. Sun, S. S., Schubert, C. M., Chumlea, W. C., Roche, A. F., Kulin, H. E., Lee, P. A., et al. (2002). National estimates of the timing of sexual maturation and racial differences among US children. Pediatrics, 110, 911–919.CrossRefGoogle Scholar
  59. Teilmann, G., Pedersen, C. B., Jensen, T. K., Skakkebaek, N. E., & Juul, A. (2005). Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics, 116, 1323–1328.CrossRefGoogle Scholar
  60. Teilmann, G., Pedersen, C. B., Skakkebaek, N. E., & Jensen, T. K. (2006). Increased risk of precocious puberty in internationally adopted children in Denmark. Pediatrics, 118, e391–e399.CrossRefGoogle Scholar
  61. Varayoud, J., Monje, L., Bernhardt, T., Muñoz-de-Toro, M., Luque, E. H., & Ramos, J. G. (2008). Endosulfan modulates estrogen-dependent genes like a non-uterotrophic dose of 17beta-estradiol. Reproductive Toxicology, 26, 138–145.CrossRefGoogle Scholar
  62. Vasiliu, O., Muttineni, J., & Karmaus, W. (2004). In utero exposure to organochlorines and age at menarche. Human Reproduction, 19, 1506–1512.CrossRefGoogle Scholar
  63. Wohlfahrt-Veje, C., Andersen, H. R., Jensen, T. K., Grandjean, P., Skakkebæk, N. E., & Main, K. M. (2009). Long-term effects of prenatal pesticide exposure on several endocrine functions in children. Hormone Research, 72, 428–429.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Samim Ozen
    • 1
    Email author
  • Sukran Darcan
    • 1
  • Petek Bayindir
    • 2
  • Ercument Karasulu
    • 3
  • Damla Goksen Simsek
    • 1
  • Tahir Gurler
    • 4
  1. 1.Department of Pediatric Endocrinology and MetabolismEge University School of MedicineIzmirTurkey
  2. 2.Department of RadiologyEge University School of MedicineIzmirTurkey
  3. 3.Center for Drug Resarch and Pharmacokinetic ApplicationsEge UniversityIzmirTurkey
  4. 4.Deparment of Plastic and Reconstructive SurgeryEge University School of MedicineIzmirTurkey

Personalised recommendations