Association between lead and cadmium and reproductive hormones in peripubertal U.S. Girls

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 Tird 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 signifcantly 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.