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

以前关于青春期提前的研究集中在特定的亚群或临床人群，缺乏关于青春期提前模式的数据，即在6至8岁的儿童中，缺乏具有全国代表性的样本。 有必要确定全国性的青春期开始年龄是否下降，特别是考虑到两个问题：（1）青春期提前与儿童超重和肥胖增加的全国趋势交织在一起，（2）与正常的青春期提前相比，定义性早熟的年龄限制应该降低，以适应怀疑的长期下降。此外，有证据表明，接触环境毒素，如环境铅和内分泌干扰物，可能对激素水平和青春期的开始产生不利影响。然而，关于环境毒物如何以及是否可能与青春期开始的下降有关或有助于青春期开始的延迟的数据很少，并且通常仅限于年龄较大的儿童和青少年。 对作为第三次全国健康和营养检查调查的一部分检查的6-11岁儿童的储存生物标本（血清）进行分析有两个目的（NHANES III），1988-94年：（1）通过激素测定来估计（男孩和女孩的促黄体生成素[LH]和促黄体生成素B，男孩的睾酮）在全国代表性的6-11岁儿童样本中青春期发育开始的时间，以及激素指标和基于身体成熟的青春期开始之间的一致性（坦纳性成熟评分）用于8-11岁的儿童;以及（2）根据坦纳评分确定血铅（Pb）水平与发育迟缓之间的联系是否符合最新研究结果（阴毛）和初潮年龄的女孩可以确认的激素分析，并扩展到年轻的年龄，并确定是否有影响的血液铅水平的成熟时间为年轻的男孩。 为了实现研究目标，这些分析的目标样本是6-11岁的儿童，作为1988- 1994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岁儿童的储存血清量有限，因此选择用于分析以检测青春期开始的两种主要激素，以提供最大灵敏度（使用最少血清样本，0.2 mL），并且可以对男孩和女孩进行分析。 按照优先顺序，我们将测量促黄体生成素（LH）和促黄体生成素B。 对于数量不足以进行两项检测的样本，将测量男孩的LH和女孩的LH，并测量男孩的LH和B。 在有足够储存样本的男孩子集上，将测量睾酮。 在青春期开始的相关性方面，NHANES III数据已经在公共领域提供，包括社会人口和人体测量，以及在8-11岁收集的坦纳评分，用于验证这些年龄段的激素指标。 由于坦纳评分或青春期开始的其他测量尚未作为随后的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，则本研究可以形成将激素分析扩展到早期的基础和理由。（NHANES I和II）和后来的NHANES（1999-2000年，2001-2002年，2003-2004年）样本，以确定国家一级青春期开始时间的长期趋势程度。 为了满足第二个目标，全血铅，此外，尿镉（Cd）已经分析了检查儿童在NHANES III。 值得注意的是，NHANES III中的6-11岁儿童出生于1977-1988年，在1988年的铅污染控制法案实际上消除了汽油中的铅之前，因此NHANES的后期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问题时有用。

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.