Department of Analytical, Environmental and Geochemistry (AMGC), Vrije Universiteit Brussel (VUB), Pleinlaan 2, 1050 Elsene, Belgium.
Department of Analytical, Environmental and Geochemistry (AMGC), Vrije Universiteit Brussel (VUB), Pleinlaan 2, 1050 Elsene, Belgium.
Environ Int. 2017 May;102:190-199. doi: 10.1016/j.envint.2017.02.014. Epub 2017 Mar 18.
Sex hormone levels and timing of sexual maturation are considered important markers for health status of adolescents in puberty, and previous research suggests they might be influenced by metal exposure. In three campaigns of the Flemish Environment and Health Study (FLEHS I 2002-2006; FLEHS II 2007-2011 and FLEHS III 2012-2015), data were collected on internal exposure to metals (Cd, Cu, Pb, Cr, Mn, Tl, Ni, Sb, Hg, As and As species) and sexual maturation in 2671 14-15years old adolescents. All metals were measured in blood and/or urine, except total- and methylmercury which were measured in hair samples. Sex hormone levels were measured in blood serum of adolescent males of the cohorts of FLEHS I and FLESH II. The use of a uniform methodology in successive campaigns allows to confirm associations between exposure and health in different cohorts and over time. Furthermore, mathematical and statistical density correction methods using creatinine or specific gravity were tested for urinary markers. Significant associations between sex hormones and maturity markers were observed in the FLEHS I and II campaigns, when both were assessed together. Regardless of the applied correction method, creatinine correction systematically introduced bias due to associations of creatinine with sex hormones and maturation markers, especially in adolescent males, while this is not the case for specific gravity. A series of exposure-response associations were found, but several involving Cd, Pb, As, Tl and Cu persisted in different FLEHS campaigns. The effects of Pb and Cu on luteinizing hormone, (free) testosterone, (free) oestradiol and maturation support a xenoestrogenic agonistic action on the feedback of oestradiol to the hypothalamus-pituitary-gonadal axis. Our results suggest that specific care should be taken when selecting urine density correction for investigating associations with hormonal and maturation markers in adolescent males. Furthermore, the possibility of xenoestrogenic effects of certain metals in environmentally exposed adolescents warrants further investigation.
性激素水平和性成熟时间被认为是青春期青少年健康状况的重要标志，先前的研究表明，它们可能受到金属暴露的影响。在 Flemish Environment and Health Study（FLEHS）的三次活动（2002-2006 年的 FLEHS I；2007-2011 年的 FLEHS II 和 2012-2015 年的 FLEHS III）中，收集了 2671 名 14-15 岁青少年的内部金属暴露（Cd、Cu、Pb、Cr、Mn、Tl、Ni、Sb、Hg、As 和 As 物种）和性成熟数据。除了总汞和甲基汞在头发样本中测量外，所有金属均在血液和/或尿液中测量。FLEHS I 和 FLEHS II 队列的青少年男性血液中测量了性激素水平。在不同的队列和时间内使用统一的方法学可以确认暴露与健康之间的关联。此外，还测试了数学和统计密度校正方法，使用肌酐或比重校正尿液标志物。在 FLEHS I 和 II 活动中，当同时评估时，观察到性激素和成熟标志物之间存在显著关联。无论应用哪种校正方法，肌酐校正系统地引入了由于肌酐与性激素和成熟标志物的关联而产生的偏差，尤其是在青少年男性中，而比重则不是这种情况。发现了一系列暴露-反应关联，但在不同的 FLEHS 活动中，有几个涉及 Cd、Pb、As、Tl 和 Cu 的关联仍然存在。Pb 和 Cu 对黄体生成素、（游离）睾酮、（游离）雌二醇和成熟的影响支持了它们对雌激素反馈到下丘脑-垂体-性腺轴的拟雌激素激动作用。我们的结果表明，在选择尿液密度校正以研究与青少年男性的激素和成熟标志物的关联时，应特别注意。此外，某些金属在环境暴露的青少年中具有拟雌激素作用的可能性需要进一步研究。
