Mendiola Jaime, Meeker John D, Jørgensen Niels, Andersson Anna-Maria, Liu Fan, Calafat Antonia M, Redmon J Bruce, Drobnis Erma Z, Sparks Amy E, Wang Christina, Hauser Russ, Swan Shanna H
Department of Obstetrics and Gynecology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
J Androl. 2012 May-Jun;33(3):488-98. doi: 10.2164/jandrol.111.013557. Epub 2011 May 19.
Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families and partners in infertile couples from Massachusetts General Hospital infertility clinic. The observed associations between phthalate metabolites and reproductive hormones were robust and insensitive to the characteristics of the subpopulation or the laboratory in which the hormones were measured, despite the fact that these 2 populations span a range of fertility, urinary phthalate metabolites, and reproductive hormone levels. We therefore examined associations between urinary metabolites of DEHP and reproductive hormones-follicle-stimulating hormone, luteinizing hormone, testosterone (T), inhibin B, and estradiol (E(2))-and sex hormone-binding globulin (SHBG) in the pooled population. The magnitude of the associations seen were similar to those reported for each population separately, but effect estimates were more precise because of the increased sample size and the greater range of phthalate metabolite concentrations and hormone levels. Urinary concentrations of 3 metabolites of DEHP [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were inversely associated with the free androgen index (FAI = T/SHBG) and calculated free testosterone. Urinary concentrations of MEHHP and MEOHP were positively associated with SHBG, and MEHP was inversely associated with E(2). No other phthalate metabolites were associated with serum hormones, consistent with results in each population. Our results in this diverse population suggest that DEHP exposure is robustly associated with some male sex steroid hormones.
先前的研究表明，在美国两个不同人群中，抗雄激素外源性物质邻苯二甲酸二（2-乙基己基）酯（DEHP）的尿液代谢物浓度与几种激素的血清水平存在微弱关联：参与未来家庭研究的孕妇伴侣以及来自马萨诸塞州总医院不孕不育诊所的不孕夫妇伴侣。尽管这两个人群在生育能力、尿液邻苯二甲酸酯代谢物和生殖激素水平方面存在差异，但邻苯二甲酸酯代谢物与生殖激素之间观察到的关联是显著的，并且不受亚人群特征或测量激素的实验室的影响。因此，我们在合并人群中研究了DEHP的尿液代谢物与生殖激素——促卵泡激素、促黄体生成素、睾酮（T）、抑制素B和雌二醇（E2）——以及性激素结合球蛋白（SHBG）之间的关联。观察到的关联程度与分别针对每个人群报告的结果相似，但由于样本量增加以及邻苯二甲酸酯代谢物浓度和激素水平范围更广，效应估计更为精确。DEHP的3种代谢物[邻苯二甲酸单（2-乙基己基）酯（MEHP）、邻苯二甲酸单（2-乙基-5-羟基己基）酯（MEHHP）和邻苯二甲酸单（2-乙基-5-氧代己基）酯（MEOHP）]的尿液浓度与游离雄激素指数（FAI = T/SHBG）和计算得出的游离睾酮呈负相关。MEHHP和MEOHP的尿液浓度与SHBG呈正相关，而MEHP与E2呈负相关。没有其他邻苯二甲酸酯代谢物与血清激素相关，这与每个人群的结果一致。我们在这个多样化人群中的研究结果表明，DEHP暴露与某些男性性类固醇激素存在显著关联。
