Authors
Wu, T., Buck, GM., Mendola, P.

Title
Blood lead levels and sexual maturation in U.S. girls: The Third National Health and Nutrition Examination Survey, 1988-94.

Journal
EEnvironmental Health Perspectives, online February 4, 2003

Summary
Lead is a ubiquitous contaminant and a known neurotoxicant at low levels. Currently, the U.S. Centers for Disease Control have defined elevated lead as blood levels greater than 10 ug/dl. Past experimental studies suggested that lead exposures in the prenatal or juvenile periods also delayed puberty and sexual maturation. However, the exposure levels in these studies were not clearly defined or were unrealistically high, making the results irrelevant to humans. Few human studies have explored the subtle effects, if any, that lead has on puberty and sexual maturation.

The objectives of this study were to compare blood lead levels and puberty milestones in U.S. girls. Data from the Third National Health and Nutrition Examination Survey, 1988-94 (NHANES III) was utilized for the study. The NHANES III was a cross-sectional survey that used multi-stage probability sampling to obtain national representatives of non-institutionalized U.S. residents in 5 states and the District of Columbia. In the current study there were 1706 girls aged 8 to 16 years with established blood levels and puberty staging, according to Marshall and Tanner (1969, 1970). Menarche status was ascertained for girls 10 years of age or older (n=1235 of the 1706 girls) and blood samples were collected during each physical examination.

In the analysis other factors such as race/ethnicity, age, family size, residence, poverty income ratio, body mass index, and the design features of the study were taken into account. Blood lead levels ranged from 0.7-21.7 ug/dl. The results showed that children who were at the lower pubertal stages tended to have higher levels of lead in their blood. Children with blood lead levels between 2.1-4.9 ug/l and 5.0-21.7 ug/l had a negative association with both pubic hair growth (OR=0.48, 95% CI=0.25, 0.92, and OR=0.27, 95% CI=0.08, 0.93) and attainment of menarche (OR=0.42, 95% CI=0.18, 0.97 and OR=0.19, 95% CI=0.08, 0.43). No association was established with breast development.

Importantly, this study chose to use direct blood measurement which gives a more accurate measure of exposure. The results suggested that blood lead levels between 2.1 and 21.7 ug/dl were negatively associated with both pubic hair growth and menarche. However, there are two points to consider before drawing conclusions from this analysis. First, the biological mechanism by which lead could potentially alter sexual development and puberty is poorly understood and largely speculative at this time. At very low concentrations lead is a known neurotoxicant (5 ug/dl and above) while effects on reproductive hormones only begin to appear at concentrations greater than 40 ug/dl. Some mechanisms by which lead may alter hormone profiles include: (1) alteration in gonadotropin levels; and (2) changes in intracellular calcium homeostasis inducing neurotoxicity that may also account for changes in pituitary gonadotropin secretion. Second, the trigger for puberty has not yet been established. There are several known risk factors that have shown to alter the transition into puberty including diet, health status, physical activity and estrogen exposure that were not taken into consideration in this analysis. Nevertheless, this study does warrant further research into the possible mechanisms by which lead could alter puberty.