Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls
Introduction
Menarche, or the first menstrual period, marks the beginning of a woman’s reproductive life. Earlier or later onset has been linked with risk of chronic disease in adulthood. Its decline from about 18–12 years of age over 300 years is explained by lifestyle changes that accompanied industrialization. Primary factors are a girl’s age, adiposity, and race. Individual factors such as race and body mass index (BMI) account for 6–12 months difference in menarche [1], [2]. Racial differences may reflect both genetic and environmental factors. Much but not all of variation in menarche is explained by genetics, perhaps 70% [3]. These observations, in combination with strong experimental evidence that some chemical exposures alter pubertal timing, have triggered research regarding whether environment influences menarche [4]. Most research has come from cross-sectional investigations that assess environmental exposures among girls over a range of ages. Cross-sectional designs may not be able to address adequately the question of temporality needed to evaluate exposures in relation to menarche.
We are interested in highly prevalent hormonally active environmental exposures that have been identified in the past 20 years [5]. Common sources are diet and the physical environment, including household and personal care products. Among these, a number of phthalates and phenols, including phytoestrogens, have exhibited agonist and antagonistic hormone activity as well as possible obesogenic and anti-obesogenic effects. Estrogen, androgen, thyroid, and peroxisome proliferator-activated receptor (PPAR) activity has been observed [6].
To examine relationships between such exposures and pubertal onset, the NCI and NIEHS established the Breast Cancer and Environment Research Program (BCERP) cohort of girls to enable longitudinal study during childhood [7]. Here we report associations of 19 urinary biomarkers of environmental exposures with menarche in the BCERP cohort.
Section snippets
Study design and data collection
The BCERP Puberty Study is a cohort that enrolled girls between 2004 and 2007, concluding in 2015 (up to eleven years’ follow-up or 9 annual visits). Study sites included Icahn School of Medicine at Mount Sinai (NYC) that recruited black or Hispanic girls mainly from East Harlem in New York City; Cincinnati Children’s Hospital (Cincinnati) that recruited from the greater Cincinnati metropolitan area; and Kaiser Permanente Northern California (California) that recruited members of the KPNC
Results
The BCERP cohort is a culturally diverse group of girls who were enrolled at 6–8 years of age and followed through 2015, for eight-to-eleven years depending on year of enrolment. Of the 1051 girls in our analysis, menarche occurred at 12.2 years of age among 912 girls (median 146 months, IQR 135–156). Girls who reported menarche were 137 months old at the pre-menarche visit immediately before (median, IQR 126–148; n = 912). Girls who never reported having a period (n = 139) were somewhat younger at
Discussion
Age of menarche in the BCERP cohort was associated with two urinary phenols and one phthalate metabolite which had been measured several years earlier. Menarche on average occurred 7 months younger with higher 2,5-dichlorophenol and 4–5 months older with enterolactone and MCPP. Exposure effects were similar for age at first breast development (adjusted; Table 5) but not pubarche, which is not estrogen dependent. Pubertal changes associated with these exposures were reflected in hazards ratios
Conclusion
In this prospective study of environmental biomarkers measured as long as ten years before puberty, we find three to be associated with timing of both breast development and menarche; two others were associated with breast development but not menarche. Six other biomarkers or composite indices were associated with neither. Little is known about the relative biological effects and exposure thresholds that govern the pubertal trajectory. The timing of exposure measurement in this study may
Funding
This research was supported by the Breast Cancer and the Environment Research Program (BCERP) award numbers U01ES012770, U01ES012771, U01ES012800, U01ES012801, U01ES019435, U01ES019453, U01ES019454, U01ES019457, and by R827039, P01ES009584, P30ES006096, P30ES023515 from the National Institute of Environmental Health Sciences (NIEHS), the National Cancer Institute (NCI), EPA, NIH, DHHS, CSTA-UL1RR029887, NYS Empire Clinical Research Investigator Program, Pediatric Environmental Health Fellowship
Acknowledgments
We gratefully acknowledge our collaborators at the centers involved in this research including Jessica Montana, Nancy Mervish, Cheryl Stein, Rochelle Osborne, Lisa Boguski, Joel Forman, and Barbara Brenner (MSSM); Gayle Greenberg, Peggy Monroe, Bob Bornschein (Cincinnati); Robert Hiatt, Louise Greenspan, Julie Deardorff, Janice Barlow (Kaiser Permanente). We also thank Daniel L. Parker, Amber Bishop, Ella Samandar, Jim Preau and Tao Jia for measurement of the environmental biomarkers.
References (47)
- et al.
Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States
Environ. Res.
(2008) - et al.
Adjustment for total energy intake in epidemiologic studies
Am. J. Clin. Nutr.
(1997) - et al.
Environmental phenols and pubertal development in girls
Environ. Int.
(2015) - et al.
Dietary flavonol intake is associated with age of puberty in a longitudinal cohort of girls
Nutr. Res.
(2013) - et al.
Environmental exposures and puberty in inner-city girls
Environ. Res.
(2008) - et al.
Urinary bisphenol A and age at menarche among adolescent girls: evidence from NHANES 2003–2010
Environ. Res.
(2015) - et al.
In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation
Environ. Res.
(2014) - 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) - et al.
Pubertal correlates in black and white girls
J. Pediatr.
(2006) - et al.
Identifying sources of phthalate exposure with human biomonitoring: results of a 48 h fasting study with urine collection and personal activity patterns
Int. J. Hyg. Environ. Health
(2013)
Development and application of simple pharmacokinetic models to study human exposure to di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP)
Environ. Int.
Dietary predictors of urinary environmental biomarkers in young girls, BCERP, 2004–2007
Environ. Res.
Examination of US puberty-timing data from 1940 to 1994 for secular trends: panel findings
Pediatrics
Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index
Pediatrics
The familial clustering of age at menarche in extended twin families
Behav. Genet.
Endocrine disruptors and abnormalities of pubertal development
Basic Clin. Pharmacol. Toxicol.
Endocrine disruptors: challenges for environmental research in the 21st century
Ann. N. Y. Acad. Sci.
Endocrine-disrupting chemicals: an Endocrine Society scientific statement
Endocr. Rev.
Pubertal assessment methods and baseline characteristics in a mixed longitudinal study of girls
Pediatrics
200 CDC Growth Charts: United States
Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls
Environ. Health Perspect.
Phthalate exposure and pubertal development in a longitudinal study of US girls
Hum. Reprod.
Thyroid antagonists (Perchlorate, thiocyanate, and nitrate) and childhood growth in a longitudinal study of U.S. girls
Environ. Health Perspect.
Cited by (56)
Effects of pharmaceutical and personal care products on pubertal development: Evidence from human and animal studies
2024, Environmental PollutionAssociations of maternal gestational urinary environmental phenols concentrations with bone mineral density among 12-year-old children in the HOME Study
2023, International Journal of Hygiene and Environmental HealthNew insights on the effects of endocrine-disrupting chemicals on children
2022, Jornal de PediatriaPersonal care products and cosmetics
2022, Reproductive and Developmental ToxicologyConcentrations of urinary parabens and reproductive hormones in girls 6–17 years living in Canada
2021, International Journal of Hygiene and Environmental HealthCitation Excerpt :Only a handful of human studies have examined the association between paraben exposure and reproductive development, and most have reported no association. A longitudinal cohort of girls living in the U.S. showed that urinary parabens at 6–8 years old were not associated with age at breast or pubic hair development (Wolff et al., 2015) or age at menarche (Wolff et al., 2017). Another longitudinal cohort, conducted in Chile, showed that urinary parabens measured prior to the onset of breast development and during adolescence was not associated with the age of menarche (Binder et al., 2018).