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首页> 外文期刊>Environmental research >A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men
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A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and serum reproductive hormones in men

机译：对美沙拉敏药物和男性血清生殖激素的邻苯二甲酸二丁酯接触的交叉交叉前瞻性研究

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摘要

Background: Phthalates, such as dibutyl phthalate (DBP), are endocrine disrupters used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD). Objectives: Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (> 1000x background) altered serum hormones. Methods: Men (N = 73) with IBD participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background) at baseline crossed-over for 4 months to DBP-mesalamine (high) and then crossed-back for 4 months to non-DBP mesalamine (B_1HB_2-arm) and vice versa for men on DBP-mesalamine at baseline (H_1BH_2-arm). We divided H_1BH_2-arm at the median (H_1 < 3yrs or H_1 ≥ 3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models. Results: When B_1HB_2-arm (26 men,134 samples) crossed-over, luteinizing hormone decreased 13.9% (95% confidence interval(CI): -23.6,-3.0) and testosterone, inhibin-B, and follicle-stimulating hormone (FSH) marginally decreased; after crossback all increased 8-14%. H_1BH_2-arm, H_1 ≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H_1BH_2-arm,H_1 < 3yrs (22 men,100 samples) after crossover, inhibin-B increased 13.2% (CI: 4.2,22.9), FSH decreased 9.9% (CI: -17.9,-1.1) and after crossback, inhibin-B further increased 11.3%, and FSH marginally increased. Conclusions: High-DBP exposure may disrupt pituitary-gonadal hormones that largely reversed after exposure removal, but only in men with no or short previous high-exposure history. Paradoxically, men with longer duration of high-DBP exposure, exposure removal did not change hormone levels, suggesting that long-term high-DBP exposure may alter the pituitary-gonadal axis and make it insensitive to exposure changes.
机译：背景：邻苯二甲酸二丁酯（DBP）等邻苯二甲酸酯是内分泌干扰物，用于某些药物涂层（如美沙拉敏）中，以治疗炎症性肠病（IBD）。目的：利用有/无DBP的不同美沙拉敏配方，我们评估了美沙拉敏（> 1000x背景）的DBP是否改变了血清激素。方法：患有IBD的男性（N = 73）参加了一项crossover-crossback前瞻性研究，并提供了多达6份血清样本（2：基线，2：crossover，2：crossback）。基线时非DBP美沙拉敏（背景）的男性与DBP-美沙拉敏（高）交叉4个月，然后向非DBP美沙拉敏（B_1HB_2-arm）交叉4个月，反之亦然。基线时为美沙拉敏（H_1BH_2-臂）。我们按中位数（H_1 <3yrs或H_1≥3yrs）划分H_1BH_2-arm。我们使用多变量线性混合效应模型估算了血清生殖激素的交叉和交叉百分比变化。结果：当B_1HB_2臂（26名男性，134个样本）交叉时，黄体生成激素降低了13.9％（95％置信区间（CI）：-23.6，-3.0），睾丸激素，抑制素B和促卵泡激素（ FSH）略有下降；交叉后所有增加了8-14％。 H_1BH_2臂，H_1≥3岁（25名男性，107个样本）在交叉或交叉时无变化，而H_1BH_2臂，H_1 <3yrs（22名男性，100个样本），交叉后抑制素-B增加了13.2％（CI：4.2， 22.9），FSH下降9.9％（CI：-17.9，-1.1），交叉后，抑制素B进一步上升11.3％，FSH略有上升。结论：高DBP暴露可能会破坏垂体性腺激素，而这些激素在去除暴露后会大大逆转，但仅适用于以前没有高暴露史或短暂高暴露史的男性。矛盾的是，长时间接触高DBP的男性，去除接触并没有改变激素水平，这表明长期高DBP接触可能会改变垂体-性腺轴并使其对接触变化不敏感。

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  • 来源
    《Environmental research》 |2018年第1期|121-131|共11页
  • 作者

    Feiby L. Nassan; Brent A. Coull; Niels E. Skakkebaek; Anna-Maria Andersson; Michelle A. Williams; Lidia Minguez-Alarcon; Stephen A. Krawetz; Janet E. Hall; Elizabeth J. Hait; Joshua R. Korzenik; Jennifer B. Ford; Alan C. Moss; Russ Hauser;

  • 作者单位

    Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA;

    Department of Biostatistics, Harvard T.H Chan School of Public Health, Boston, MA, USA;

    University Department of Growth and Reproduction, and EDMaRC, Rigshospitalet, Copenhagen, Denmark;

    University Department of Growth and Reproduction, and EDMaRC, Rigshospitalet, Copenhagen, Denmark;

    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA;

    Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA;

    Department of Obstetrics & Gynecology, Center for Molecular Medicine & Genetics, Wayne State University, Detroit, MI, USA;

    Division of Intramural Research, NIH/NIEHS, NC, USA;

    Division of Gastroenterology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA;

    Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;

    Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA;

    Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;

    Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA,Vincent Obstetrics and Gynecology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA;

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  • 正文语种 eng
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  • 关键词

    Phthalate; Endocrine disruptor; Crossover study; Hormones; Men;

    机译：邻苯二甲酸盐内分泌干​​扰物;交叉研究;激素;男装;

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