Abstract：
Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD).
Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (>1000x background) altered serum hormones.
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 (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). We divided H1BH2-arm at the median (H1<3yrs or H1≥3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models.
When B1HB2-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%. H1BH2-arm, H1≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H1BH2-arm,H1<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.
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.
Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (>1000x background) altered serum hormones.
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 (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). We divided H1BH2-arm at the median (H1<3yrs or H1≥3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models.
When B1HB2-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%. H1BH2-arm, H1≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H1BH2-arm,H1<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.
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.
摘要：
邻苯二甲酸酯,如邻苯二甲酸二丁酯(DBP)，是一些药物涂层中使用的内分泌干扰物，例如，美沙拉嗪治疗炎症性肠病（IBD）。
利用含/不含DBP的不同美沙拉嗪配方，我们评估了来自美沙拉嗪的DBP(>1000x背景)是否改变了血清激素。
患有IBD的男性（N=73）参加了交叉-交叉前瞻性研究，并提供了多达6份血清样本（2：基线，2：交叉，2：crossback）。基线时使用非DBP美沙拉嗪（背景）的男性与DBP-美沙拉嗪（高）交叉4个月，然后交叉4个月与非DBP美沙拉嗪（B1HB2臂），反之亦然，基线时使用DBP-美沙拉嗪的男性（S1BH2臂）。我们将H1BH2臂分为中位数（H1<3年或H1≥3年）。我们使用多变量线性混合效应模型估计了血清生殖激素的交叉和交叉百分比变化。
当B1HB2-arm（26人，134个样本)交叉，黄体生成素下降13.9%（95%置信区间（CI）：-23.6，-3.0）和睾酮，抑制素-B,卵泡刺激素（FSH）略有下降；交叉后全部增加8-14％。H1BH2臂,H1≥3年(25名男性，107个样本)在交叉或交叉时没有变化，而在H1BH2臂中，H1<3年（22名男性，100个样本)交叉后，抑制素B增加13.2%（CI：4.2,22.9），FSH下降9.9%（CI：-17.9，-1.1），抑制素-B进一步增加11.3%,FSH略有增加。
高DBP暴露可能会破坏垂体-性腺激素，这些激素在暴露去除后基本上逆转，但仅限于没有或短暂的高暴露史的男性。矛盾的是,高DBP暴露时间较长的男性，去除暴露并没有改变激素水平，提示长期高DBP暴露可能改变垂体-性腺轴,使其对暴露变化不敏感.
利用含/不含DBP的不同美沙拉嗪配方，我们评估了来自美沙拉嗪的DBP(>1000x背景)是否改变了血清激素。
患有IBD的男性（N=73）参加了交叉-交叉前瞻性研究，并提供了多达6份血清样本（2：基线，2：交叉，2：crossback）。基线时使用非DBP美沙拉嗪（背景）的男性与DBP-美沙拉嗪（高）交叉4个月，然后交叉4个月与非DBP美沙拉嗪（B1HB2臂），反之亦然，基线时使用DBP-美沙拉嗪的男性（S1BH2臂）。我们将H1BH2臂分为中位数（H1<3年或H1≥3年）。我们使用多变量线性混合效应模型估计了血清生殖激素的交叉和交叉百分比变化。
当B1HB2-arm（26人，134个样本)交叉，黄体生成素下降13.9%（95%置信区间（CI）：-23.6，-3.0）和睾酮，抑制素-B,卵泡刺激素（FSH）略有下降；交叉后全部增加8-14％。H1BH2臂,H1≥3年(25名男性，107个样本)在交叉或交叉时没有变化，而在H1BH2臂中，H1<3年（22名男性，100个样本)交叉后，抑制素B增加13.2%（CI：4.2,22.9），FSH下降9.9%（CI：-17.9，-1.1），抑制素-B进一步增加11.3%,FSH略有增加。
高DBP暴露可能会破坏垂体-性腺激素，这些激素在暴露去除后基本上逆转，但仅限于没有或短暂的高暴露史的男性。矛盾的是,高DBP暴露时间较长的男性，去除暴露并没有改变激素水平，提示长期高DBP暴露可能改变垂体-性腺轴,使其对暴露变化不敏感.
