Association between Lead and Cadmium and Reproductive Hormones in Peripubertal U.S. Girls

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Abstract

Background

Lead (Pb) and cadmium (Cd) are known reproductive toxicants thought to disrupt hormone production throughout sensitive developmental windows, although this has not been previously examined in nationally representative peripubertal children.

Objectives

We examined the association between blood Pb and urinary Cd concentrations and the reproductive hormones inhibin B and luteinizing hormone (LH) in girls 6–11 years of age who participated in the cross-sectional Third National Health and Nutrition Examination Survey (NHANES III) (1988–1994).

Methods

Pb (micrograms per deciliter) was measured in whole blood, and Cd was measured in urine (nanograms per milliliter). Inhibin B (picograms per milliliter) and LH (milli–International units per milliliter) were measured in residual sera for 705 girls. Survey logistic regression was used to estimate associations with pubertal onset based on inhibin B concentration > 35 pg/mL or LH concentration > 0.4 mIU/mL, and multinomial logistic regression was used to estimate the association between Pb and increasing categories of hormone concentrations.

Results

High Pb (≥ 5 μg/dL) was inversely associated with inhibin B > 35 pg/mL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.11–0.60; compared with Pb < 1 μg/dL]. At 10 and 11 years of age, girls with low Pb (< 1 μg/dL) had significantly higher inhibin B than did girls with moderate (1–4.99 μg/dL) or high Pb (≥ 5 μg/dL). In the subsample of 260 girls with levels of inhibin B above the level of detection and using survey regression modeling, inhibin B levels were lower among girls with both high Pb and high Cd (β = −0.52; 95% CI, −0.09 to −1.04) than among girls with high Pb alone (β = −0.35; 95% CI, −0.13 to −0.57), relative to girls with low Pb and low Cd.

Conclusions

Higher Pb was inversely associated with inhibin B, a marker of follicular development, and estimated effects suggestive of pubertal delays appeared to be stronger in the context of higher Cd concentrations. These data underscore the importance of Pb and Cd as reproductive toxicants for young girls.

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Most cited references 47

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Examination of US puberty-timing data from 1940 to 1994 for secular trends: panel findings.

Michelle M. Giddens, P Lee, Shanna Swan … (2008)

Whether children, especially girls, are entering and progressing through puberty earlier today than in the mid-1900s has been debated. Secular trend analysis, based on available data, is limited by data comparability among studies in different populations, in different periods of time, and using different methods. As a result, conclusions from data comparisons have not been consistent. An expert panel was asked to evaluate the weight of evidence for whether the data, collected from 1940 to 1994, are sufficient to suggest or establish a secular trend in the timing of puberty markers in US boys or girls. A majority of the panelists agreed that data are sufficient to suggest a trend toward an earlier breast development onset and menarche in girls but not for other female pubertal markers. A minority of panelists concluded that the current data on girls' puberty timing for any marker are insufficient. Almost all panelists concluded, on the basis of few studies and reliability issues of some male puberty markers, that current data for boys are insufficient to evaluate secular trends in male pubertal development. The panel agreed that altered puberty timing should be considered an adverse effect, although the magnitude of change considered adverse was not assessed. The panel recommended (1) additional analyses of existing puberty-timing data to examine secular trends and trends in the temporal sequence of pubertal events; (2) the development of biomarkers for pubertal timing and methods to discriminate fat versus breast tissue, and (3) establishment of cohorts to examine pubertal markers longitudinally within the same individuals.

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Very low lead exposures and children's neurodevelopment.

David C Bellinger (2008)

We remain far from achieving the goal of eliminating lead-associated neurodevelopmental morbidities in children. New evidence regarding the blood lead levels at which morbidities occur have led to calls for the Centers for Disease Control and Prevention to reduce the current screening guideline of 10 microg/dl. The review evaluates the basis for these calls. Adverse outcomes, such as reduced intelligence quotient and academic deficits, occur at levels below 10 microg/dl. Some studies suggest that the rate of decline in performance is greater at levels below 10 microg/dl than above 10 microg/dl, although a plausible mechanism has not been identified. Increased exposure is also associated with neuropsychiatric disorders such as attention deficit hyperactivity disorder and antisocial behavior. Functional imaging studies are beginning to provide insight into the neural substrate of lead's neurodevelopmental effects. Current protocols for chelation therapy appear ineffective in preventing such effects, although environmental enrichment might do so. No level of lead exposure appears to be 'safe' and even the current 'low' levels of exposure in children are associated with neurodevelopmental deficits. Primary prevention of exposure provides the best hope of mitigating the impact of this preventable disease.

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Public health implications of altered puberty timing.

Ewa Rajpert-De Meyts, Richard Sharpe, Jorma Toppari … (2008)

Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated with an increased risk for testicular cancer according to several, but not all, epidemiologic studies. Girls and, possibly, boys who exhibit premature adrenarche are at a higher risk for developing features of metabolic syndrome, including obesity, type 2 diabetes, and cardiovascular disease later in adulthood. Altered timing of puberty also has implications for behavioral disorders. For example, an early maturation is associated with a greater incidence of conduct and behavior disorders during adolescence. Finally, altered puberty timing is considered an adverse effect in reproductive toxicity risk assessment for chemicals. Recent US legislation has mandated improved chemical testing approaches for protecting children's health and screening for endocrine-disrupting agents, which has led to changes in the US Environmental Protection Agency's risk assessment and toxicity testing guidelines to include puberty-related assessments and to the validation of pubertal male and female rat assays for endocrine screening.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Title: Environmental Health Perspectives

Publisher: National Institute of Environmental Health Sciences

ISSN (Print): 0091-6765

ISSN (Electronic): 1552-9924

Publication date (Print): December 2010

Publication date (Electronic): 30 July 2010

Volume: 118

Issue: 12

Pages: 1782-1787

Affiliations

[1 ] Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland, USA;

[2 ] Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA;

[3 ] Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA

Author notes

Address correspondence to M. Hediger, 6100 Executive Blvd., Room 7B03, Rockville, MD 20852 USA. Telephone: (301) 435-6897. Fax: (301) 402-2084. E-mail: hedigerm@ 123456exchange.nih.gov

[*]

Current address: Department of Public Health, Shenandoah University, Winchester, VA 22601 USA. Telephone: (540) 665-4798. E-mail: agollenb@ 123456su.edu

The authors declare they have no actual or potential competing financial interests.

Article

Publisher ID: ehp-118-1782

DOI: 10.1289/ehp.1001943

PMC ID: 3002200

PubMed ID: 20675266

SO-VID: 02737006-e42c-49b3-9225-93bfba17ea41

Copyright © This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.

Association between Lead and Cadmium and Reproductive Hormones in Peripubertal U.S. Girls

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Abstract

Background

Objectives

Methods

Results

Conclusions

Related collections

Global Health Next Generation Network

Most cited references 47

Examination of US puberty-timing data from 1940 to 1994 for secular trends: panel findings.

Very low lead exposures and children's neurodevelopment.

Public health implications of altered puberty timing.

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