Blood Lead Levels and Delayed Onset of Puberty in a Longitudinal Study of Russian Boys

Abstract

Background World-wide trends towards earlier pubertal onset have raised concerns regarding the potential role of environmental exposures, including lead. Previous animal studies and studies in girls have revealed associations of lead with perturbations in pubertal onset. We evaluated the association of blood lead levels (BLLs) with pubertal onset in a longitudinal cohort of Russian boys. Methods 489 Russian boys were enrolled in 2003–2005 at ages 8–9 years and followed annually through May 2008. Cox proportional hazards models were used to evaluate the association of BLLs at enrollment with time to pubertal onset during follow-up based on testicular volume (TV) and pubertal staging, adjusting for birth characteristics, nutritional status, maternal exposures during pregnancy, height and BMI, and socioeconomic status. Results 481 boys had BLLs, with median=3 µg/dL and 28% ≥ 5 µg/dL. The percentage of pubertal boys increased with age, from 12% at age 8 to 83% at age 12 as defined by TV>3ml, from 22% to 90% as defined by genitalia stage 2 or higher, and from 4% to 40% as defined by pubic hair stage 2 or higher. After adjustment for potential confounders including BMI and height, boys with high BLLs (≥ 5 µg/dL) had a 24%–31% reduced risk of pubertal onset based on TV>3ml (Hazard Ratio (HR)= 0.73; 95% CI: 0.55, 0.97, p=0.03), genital staging (HR=0.76, 95% CI: 0.59, 0.98, p=0.04), and pubic hair staging (HR=0.69, 95% CI: 0.44, 1.07, p=0.10) as compared to those with lower lead levels. Pubertal onset occurred 6–8 months later on average for boys with high BLLs compared to those with BLLs < 5 µg/dL. Conclusions Higher blood lead was associated with later pubertal onset in this prospective study of peri-pubertal Russian boys. Given the large numbers of children with BLLs≥5 µg/dL worldwide, this shift has important public health implications and supports review of current lead policies.

Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boys

“…We also identified several predictors of male pubertal onset that were consistent with prior studies, including birth weight, caloric intake, and high BLLs (Adair 2001; Denham et al, 2005; Karaolis-Danckert et al, 2009; Ong et al, 2009; Selevan et al, 2003; Wang et al, 2012; Williams et al, 2010; Wu et al, 2003). …”

Male pubertal development: are endocrine-disrupting compounds shifting the norms?

“…In this cohort, 8-to 9-year-old boys with blood lead levels R5 mg/dl were less likely to have onset of puberty assessed by testicular volume than those with lower lead levels (Hauser et al 2008). Subsequent analysis of longitudinal data in these Russian boys showed that the delay in pubertal onset with blood lead levels R5 mg/dl was w6-8 months (Williams et al 2010). These studies confirm low-level effects of childhood lead exposures on male and female pubertal timing.…”

The association of peripubertal serum concentrations of organochlorine chemicals and blood lead with growth and pubertal development in a longitudinal cohort of boys: a review of published results from the Russian Children’s Study

“…The RCS is a prospective cohort of 516 8 to 9 year old boys who resided in Chapaevsk between 2003–2005 (10, 20, 21). After study enrollment, they were followed annually through 18 to 19 years of age.…”

“…Lipid-standardized concentrations were used for DLCs, TEQs and NDL-PCBs, and wet-weight concentrations were used with total lipids included as a covariate in the OCP models. We initially assessed the cross-sectional associations of high vs. low BLL with pubertal onset status at study entry using adjusted logistic regression models (37), and subsequently evaluated the longitudinal association of lead with pubertal onset using multivariable Cox proportional hazard models for time to pubertal onset (20). SAS (SAS Institute, Cary NC) was used for all analyses.…”