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Phthalate exposure and pubertal development in a longitudinal study of US girls.

M.S. Wolff(1), S.L. Teitebaum(1), K. McGovern(1), G.C. Windham(2), S.M. Pinney(3), M. Galvez(1), A.M. Calafate(4), L.H. Kushi(5), and F.M. Biro(6) on behalf of the Breast Cancer and the Environment Research Program.

  1. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
  2. Division of Environmental and Occupational Disease Control, California Department of Public Health., Richmond, CA.
  3. Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH.
  4. U.S. Centers for Disease Control and Prevention, Atlanta, GA.
  5. Division of Research, Kaiser Permanente, Oakland, CA.
  6. Division of Adolescent Medicine, Cincinnati Children’s Hospital, Cincinnati, OH.

Hum.Reprod.(2014) 29(7):1558-1566.
Doi:10.1093/humrep/due081

Lay Abstract 

This paper, published in the April 2014 issue of Human Reproduction, presents results of a study investigating whether phthalate exposure during early childhood altered the timing of pubertal development in girls. Phthalates are widespread hormonally active pollutants suspected of being able to alter early development, with possible effects on pubertal onset,including age at breast and pubic hair onset and age at menarche.

The study followed a multi-ethnic cohort of 1239 girls from New York City, greater Cincinnati, and the San Francisco Bay area. Girls were 6-8 years old at enrollment during the period of 2004-2007 and were followed until 2011. Study investigators sought to both evaluate the association between age at pubertal onset and phthalate exposure and whether a relationship between phthalate exposure and pubertal onset is modified by obesity. Previous studies have shown mixed results. In female rats, phthalates exhibited differing effects, suggesting that pubertal development might be accelerated or delayed depending on timing, dose and other factors. Two reports, in cross sectional -study design, have found later pubertal development from phthalate exposures However, an analysis of general population data from the U.S. National Health and Nutrition Examination Survey(NHANES) found no relationship between phthalate exposures and menarche. The Wolff, et al study is the first longitudinal study, to the authors’ knowledge, looking at timing of pubertal onset in girls in relation to phthalate exposures.

Phthalate metabolites were measured in urine collected at enrollment from 1,170 girls with concentrations ranging from low to very high. Breast and pubic hair stages and body size were assessed one to two times annually to determine the age at transition from Stage 1(no breast or pubic hair development) to Stage 2(evidence of breast or pubic hair development).  Associations were examined with respect to age-specific body mass-index(BMI) percentile, one of the strongest predictors of pubertal onset.

The authors found that exposures of high molecular weight phthalate (MWP) metabolites were associated with later pubic hair development during 7 years of observation.  For girls in the study, a 10 fold higher exposure to high MWP was associated with the transition from pubic hair stage 1(PH1) to PH2(stage 2) being later by 8 months. The relationship was stronger among normal weight girls.  Among normal-weight girls, age at pubic hair stage 2 was 9.5 months older for girls with the highest exposure levels. No associations were observed between low-molecular weight phthalate urinary metabolite concentrations and age at pubertal transition.  High MWP come from structural or household products while low MWP come mainly from personal care products, especially those with fragrance.

These results raise a number of questions. While there is evidence that phthalate exposures are fairly consistent over time, the exposure measure in this study may not reflect an earlier, more susceptible window of exposures.  It is possible that later breast development could mean a shorter, incomplete window during which the breast components develop. It could also mean that later development is better because lifetime hormone exposures would be less.


Phthalate exposures, hormonally active pollutants that may alter pubertal timing, are widespread; children’s absorbed levels are higher than adults(CDC,2009).  More than 10% of the girls in this study had urinary biomarker levels that were very high for both high-MWP or low-MWP.  Thus, understanding the impact of phthalates on development has public health significance; there is a need to integrate lifetime exposure, especially prenatal through infancy where susceptibility may be greatest. Whether pre-pubertal exposures delay or accelerate pubertal development may depend on age at exposure as well as other factors such as obesity and exposures earlier in life. Whether exposures act independently or as part of real life mixtures may also change their effects on maturation from birth through childhood. There is a need to move beyond the examination of single phthalate exposures or even groupings of similar phthalates(as was done in the analysis of this study) toward considering the effects of a combinations of chemicals.   Key questions to be answered are:

  • Do childhood exposures add to earlier life insults or act alone?
  • How variable might phthalate exposures be over early life? 
  • How much do effects vary with age of exposure?
  • What environmental agents are more likely to be detectable for delayed rather than early puberty?
  • If the size of these effects are likely to be small, what models are available to provide adequate statistical power and analysis?

This research was supported by the Breast Cancer and the Environment Research Program(BCERP) supported by the National Institute of Environmental Health Sciences(NIEHS), the National Cancer Institute(NCI), Environmental Protection Agency(EPA), the NYS Empire Clinical Research Investigator Program, Pediatric Environmental Health Fellowship and the Avon Foundation.