Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, United States; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, United States.
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, United States; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, United States.
Environ Int. 2023 Feb;172:107771. doi: 10.1016/j.envint.2023.107771. Epub 2023 Jan 24.
BACKGROUND/OBJECTIVES: Women are ubiquitously exposed to endocrine disruptors, including phthalates. Ovarian follicles undergoing folliculogenesis (indirectly measured by ovarian volume) produce anti-Müllerian hormone (AMH) and estradiol (E2). We evaluated associations of phthalates with ovarian volume to assess whether this explained prior positive associations of phthalates with AMH and E2.
Women ages 45-54 years (n = 614) had transvaginal ultrasounds of right/left ovaries to calculate mean ovarian volume. Women provided up-to-four urine and blood samples for quantifying AMH (first serum sample), E2 (all serum samples), and nine phthalate metabolites (from pooled urine, representing six parent phthalates). Multivariable linear or logistic regression models (for individual phthalate biomarkers), as well as weighted quantile sum (WQS) regression (for mixture analyses) evaluated associations of phthalate biomarkers with ovarian volume. Using cross-sectional mediation analysis, we assessed whether associations of phthalates with ovarian volume partially explained those of phthalates with AMH or E2.
Most women were non-Hispanic White (68%) and pre-menopausal (67%) with higher urinary phthalate metabolite concentrations than U.S. women. In single-pollutant models, 10% increases in mono(3-carboxypropyl) phthalate (MCPP) and monobenzyl phthalate (MBzP) were associated with 0.44% (95% CI: -0.02%, 0.91%) and 0.62% (95% CI: 0.02%, 1.23%) larger ovarian volumes, respectively. As a cumulative mixture, 10% increases in the phthalate mixture were associated with 2.89% larger ovarian volume (95%CI: 0.27, 5.59) with MCPP (35%) and MBzP (41%) identified as major contributors. Higher ovarian volume due to a 10% increase in MBzP (indirect effect OR: 1.004; 95% CI: 1.00, 1.01) explained 16% of the positive association between MBzP and higher AMH, whereas higher ovarian volume due to a 10% increase in MCPP (indirect effect %Δ: 0.11; 95% CI: -0.01, 0.22) explained 23% of the positive association between MCPP and E2.
In this cross-sectional study, phthalates were associated with increased ovarian volume, with implications for midlife hormone production.
背景/目的：女性普遍接触到内分泌干扰物，包括邻苯二甲酸酯。正在进行卵泡生成（间接通过卵巢体积测量）的卵泡产生抗苗勒管激素（AMH）和雌二醇（E2）。我们评估了邻苯二甲酸酯与卵巢体积的关联，以评估这是否可以解释先前邻苯二甲酸酯与 AMH 和 E2 呈正相关的原因。
45-54 岁的女性（n=614）进行了经阴道超声检查右/左卵巢以计算平均卵巢体积。女性提供了多达四个尿液和血液样本，以定量 AMH（第一个血清样本）、E2（所有血清样本）和九种邻苯二甲酸酯代谢物（来自混合尿液，代表六种母体邻苯二甲酸酯）。多变量线性或逻辑回归模型（用于个体邻苯二甲酸酯生物标志物），以及加权数量和回归（用于混合物分析）评估了邻苯二甲酸酯生物标志物与卵巢体积的关联。使用横截面中介分析，我们评估了邻苯二甲酸酯与卵巢体积的关联是否部分解释了邻苯二甲酸酯与 AMH 或 E2 的关联。
大多数女性为非西班牙裔白人（68%）和绝经前（67%），尿液中邻苯二甲酸酯代谢物浓度高于美国女性。在单污染物模型中，单（3-羧基丙基）邻苯二甲酸酯（MCPP）和单苄基邻苯二甲酸酯（MBzP）增加 10%，与卵巢体积分别增加 0.44%（95%CI：-0.02%，0.91%）和 0.62%（95%CI：0.02%，1.23%）相关。作为累积混合物，邻苯二甲酸酯混合物增加 10%与卵巢体积增加 2.89%相关（95%CI：0.27，5.59），MCPP（35%）和 MBzP（41%）被确定为主要贡献者。由于 MBzP 增加 10%导致的更高卵巢体积（间接效应 OR：1.004；95%CI：1.00，1.01）解释了 MBzP 与更高 AMH 之间正相关的 16%，而由于 MCPP 增加 10%导致的更高卵巢体积（间接效应%Δ：0.11；95%CI：-0.01，0.22）解释了 MCPP 与 E2 之间正相关的 23%。
在这项横断面研究中，邻苯二甲酸酯与卵巢体积增加有关，这对中年激素产生有影响。
