Blood lead levels and sexual maturation in U.S. girls: the Third National Health and Nutrition Examination Survey, 1988-1994 - Children's Health

Environmental Health Perspectives, May, 2003 by Tiejian Wu, Germaine M. Buck, Pauline Mendola

Using data from the Third National Health and Nutrition Examination Survey, we assessed measures of puberty in U.S. girls in relation to blood lead levels to determine whether sexual maturation may be affected by current environmental lead exposure. The study sample included 1,706 girls 8-16 years old with pubic hair and breast development information; 1,235 girls 10-16 years old supplied information on menarche. Blood lead concentrations (range = 0.7-21.7 [micro]g/dL) were categorized into three levels: 0.7-2.0, 2.1-4.9, and 5.0-21.7 [micro]g/dL. Sexual maturation markers included self-reported attainment of menarche and physician determined Tanner stage 2 pubic hair and breast development. Girls who had not reached menarche or stage 2 pubic hair had higher blood lead levels than did girls who had. For example, among girls in the three levels of blood lead described above, the unweighted percentages of 10-year-olds who had attained Tanner stage 2 pubic hair were 60.0, 51.2, and 44.4%, respectively, and for girls 12 years old who reported reaching menarche, the values were 68.0, 44.3, and 38.5%, respectively. The negative relation of blood lead levels with attainment of menarche or stage 2 pubic hair remained significant in logistic regression even after adjustment for race/ethnicity, age, family size, residence in metropolitan area, poverty income ratio, and body mass index. In conclusion, higher blood lead levels were significantly associated with delayed attainment of menarche and pubic hair among U.S. girls, but not with breast development. Key words: fecundity, lead, menarche, puberty, sexual maturation. Environ Health Perspect 111:737-741 (2003). doi:10.1289/ehp.6008 available via http://dx.doi.org/[Online 4 February 2003]

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Lead is a ubiquitous environmental contaminant whose toxicity, including reproductive and developmental effects in humans, is well known (Bellinger 1994; National Research Council 2000). Lead has been used as both a spermicide and abortifacient and has even been implicated in the rail of the ancient Roman Empire (Nriagu 1983). Although environmental and blood lead levels have declined over time (Pirkle et al. 1994), concern remains about the potential adverse impact of lead exposure on subtle aspects of child growth and development, including reproductive function. A recent study (Lanphear et al. 2000) reported cognitive deficits associated with blood lead concentration < 10 [micro]g/dL in children and adolescents. Puberty--the onset of fecundity or the biologic capacity for reproduction--represents an important yet understudied health outcome that may be altered at relatively low levels of lead exposure.

Subtle lead-related effects on sexual maturation have been reported in animal studies. For example, laboratory animals exposed to lead prenatally and/or as juveniles were reported to have experienced delayed puberty or sexual maturation (Der et al. 1974; Kimmel et al. 1980; Ronis et al. 1998b). To address these findings, we assessed measures of puberty in U.S. girls in relation to blood lead levels to determine if there was any evidence in humans that sexual maturation may be adversely affected by current environmental lead levels.

Methods

Data. We used data from the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994, to assess the relation between blood lead levels and pubertal milestones in U.S. girls. Briefly, the NHANES III is a cross-sectional survey that used a stratified multistage probability sampling design to obtain nationally representative information on the health and nutrition of the U.S. population using interviews and physical examinations (n = 39,695). The NHANES III represents the non-institutionalized civilian U.S. population 2 months or older who reside in the 50 states and the District of Columbia. Detailed information on the sample design and conduct of the NHANES III is available elsewhere (National Center for Health Statistics 1994).

Study sample. There were 7,050 girls 1-16 years old who participated in the youth sample of NHANES III. Only girls 8 years or older were eligible for Tanner staging of pubic hair and breast development (National Center for Health Statistics 1998). Our study sample is restricted to the 1,706 girls 8-16 years old who could provide information on blood lead, Tanner staging of pubic hair and breast development, and other variables of interest. Menarche was ascertained in the NHANES III for girls 10 years or older. As such, among the 1,706 girls, menarche data were available for 1,235 girls. We refer to these two samples as study samples 1 and 2, respectively.

Markers of sexual maturation. Physicians assessed pubic hair and breast development using Tanner staging (Tanner 1986) as described in the Physician Examiners Training Manual (Centers for Disease Control and Prevention 1996), which required a chaperone to be in the room. Tanner stage 2 pubic hair was defined in the study protocol as "sparse growth of long, slightly pigmented downy hair, straight or only slightly curled, appearing chiefly along the labia"; stage 2 breast development was defined as the breast bud stage or the "elevation of breast and papilla as small mound ... widening and elevation of the areola with pigmentation." For study purposes, we were interested in whether girls had reached stage 2 or more for these two puberty markers. Refusal rates for the Tanner staging varied by girl's age, with the lowest rates encountered for girls 8 years old and the highest rates for girls 15 years old. Specifically, refusal rates ranged from 8 to 15% for pubic hair staging and from 6 to 13% for breast staging. Girls 10-16 years old were asked about whether they had had a period/menstrual cycle, and the attainment of menarche was defined in this study based on the self-reported data. Among girls 10-16 years old (n = 1,973) who participated in NHANES III, 1,580 (80.1%) had information on attainment of menarche.