Hormonal Indicators of Pubertal Onset & Their Relationship to Blood Lead Levels

以前关于青春期提前开始的研究集中在特定的亚群或临床人群，缺乏具有全国代表性的样本中关于青春期开始模式的数据，即在6至8岁的儿童中。有必要确定全国青春期开始年龄是否有所下降，特别是考虑到两个问题：(1)青春期早期开始与全国儿童超重和肥胖增加的趋势相互交织，以及(2)建议与正常的青春期早期相比，定义性早熟的年龄限制应该降低，以适应可疑的长期下降。此外，有证据表明，暴露于环境毒素，如环境铅和内分泌干扰物，可能会对激素水平和青春期开始产生不利影响。然而，关于环境毒物如何以及是否可能导致青春期开始下降或延迟的数据很少，通常仅限于年龄较大的儿童和青少年。 作为1988-1994年第三次全国健康和营养检查调查(NHANES III)的一部分，对6-11岁儿童储存的生物样本(血清)的这些分析有两个目标：(1)通过激素分析(男孩和女孩的黄体生成素和抑制素B，男孩的睾酮)来估计6-11岁儿童的青春期发育开始的时间，以及8-11岁儿童的荷尔蒙指标和青春期开始之间的一致性(Tanner性成熟评分)；以及(2)确定最近基于Tanner评分(阴毛)和月经初潮年龄的女孩的血铅水平与成熟延迟之间的联系的研究结果是否可以通过激素分析得到证实，并推广到更年轻的年龄，并确定对于年轻男孩来说，血铅水平是否对成熟时间有影响。为了解决研究目标，这些分析的目标样本是6-11岁的儿童，作为1988-94年第三次全国健康和营养检查调查的一部分进行检查。由于6-11岁儿童可获得的储存血清数量有限，因此选择两种主要激素进行分析，以检测青春期的开始，以提供最高的灵敏度(使用最小血清样本，0.2毫升)，并可对男孩和女孩进行分析。按照优先顺序，我们将检测黄体生成素和抑制素B。对于数量不足的样本，男孩将检测黄体生成素B，女孩将检测黄体生成素。在储存了足够样本的一组男孩身上，将测量睾丸素。就青春期开始的相关性而言，NHANES III数据已经在公共领域获得，包括社会人口学和人体测量，以及在8-11岁收集的Tanner评分，用于验证这些年龄段的荷尔蒙指标。由于Tanner评分或青春期开始的其他测量没有作为随后的NHANES调查的一部分收集，如果发现激素是青春期发育开始的敏感指标，这项研究可以成为将激素分析扩大到较早(NHANES I和II)和较晚的NHANES(1999-2000、2001-2002、2003-2004)样本的基础和理由，以确定国家一级青春期开始时间的长期趋势的程度。 为了达到第二个目标，NHANES III已经对接受检查的儿童进行了全血铅和尿镉(Cd)的分析。值得注意的是，NHANES III中6-11岁的儿童出生在1977-1988年间，1988年的铅污染控制法案几乎消除了汽油中的铅，所以NHANES的后续迭代不太可能在回答环境铅暴露与青春期时间之间的关系的问题上同样有用。

Previous research on the early onset of puberty has focused on specific subpopulations or clinical populations, and data on the patterns of pubertal onset, that is, in children as young as ages 6 to 8 years, in a nationally representative sample are lacking. A need exists for determining if there has been a decline in the age of pubertal onset nationally, especially in light of two concerns: (1) the intertwining of early pubertal onset with national trends toward increased child overweight and obesity, and (2) suggestions that the age limit for defining precocious puberty, as compared with normal early puberty, should be lowered to accommodate the suspected secular decline. Further, evidence suggests that exposure to environmental toxins, such as environmental lead (Pb) and endocrine disrupters, may adversely affect hormone levels and pubertal onset. However, data on how and whether environmental toxicants may be implicated in the decline or contribute to a delay in pubertal onset are scarce and have generally been confined to older children and adolescents. There are two objectives of these analyses of stored biologic specimens (serum) for children, ages 6-11 years examined as part of the Third National Health and Nutrition Examination Survey (NHANES III), 1988-94: (1) to estimate by assay of hormones (luteinizing hormone [LH] and inhibin B for boys and girls, testosterone for boys) the timing of the onset of pubertal development in a nationally representative sample of children, ages 6-11 years, and the concordance between hormonal indicators and pubertal onset based on physical maturation (Tanner sexual maturation scores) for children, ages 8-11 years; and (2) to determine if the recent findings linking blood lead (Pb) levels and delayed maturation based on Tanner scores (pubic hair) and age at menarche in girls can be confirmed by hormonal analysis and extended to younger ages and to determine for young boys if there are effects of blood Pb levels on timing of maturation. To address study objectives, the target sample for these analyses is children, ages 6-11 years, examined as part of the Third National Health and Nutrition Examination Survey, 1988-94. Because limited amounts of stored sera are available for children in the 6-11 year age range, the two main hormones selected for analysis to detect the onset of puberty were chosen to provide the maximum sensitivity (using a minimum of serum sample, 0.2 mL) and can be analyzed for both boys and girls. In order of priority, we will measure luteinizing hormone (LH) and inhibin B. On those samples with insufficient quantity to do both, inhibin B will be measured for boys and LH for girls. On a subset of boys who have adequate stored sample, testosterone will be measured. In terms of correlates of pubertal onset, NHANES III data are already available in public domain, including socio-demographic and anthropometric measurements, as well as Tanner scores collected at ages 8-11, for validation of the hormonal indicators at those ages. Because Tanner scores or other measures of pubertal onset have not been collected as part of subsequent NHANES surveys, if the hormones are found to be sensitive indicators of the onset of pubertal development, this study could form the basis and justification for extending the hormone analyses to earlier (NHANES I and II) and later NHANES (1999-2000, 2001-2002, 2003-2004) samples to determine the extent of secular trends in the timing of pubertal onset at a national level. To meet the second objective, whole blood Pb and, in addition, urinary cadmium (Cd) have already been analyzed for examined children in NHANES III. It is important to note that the 6-11 year old children in NHANES III were born in the years 1977-1988, before the Lead Contamination Control Act of 1988 virtually eliminated Pb in gasoline, so it is unlikely that later iterations of NHANES will be as useful in answering the question about the relationship between environmental Pb exposure and timing of puberty.