Abstract：
BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition.
METHODS: Pre- and perimenopausal women from the Midlife Women\'s Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally.
RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures.
CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.
METHODS: Pre- and perimenopausal women from the Midlife Women\'s Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally.
RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures.
CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.
摘要：
背景：更年期过渡涉及明显的性激素变化。环境化学品,如尿邻苯二甲酸盐代谢物，在横断面研究中与性激素水平相关。很少有研究评估绝经过渡期尿邻苯二甲酸酯代谢物浓度与性激素水平之间的纵向关联。
方法：来自中年妇女健康研究（MWHS）（n=751）的绝经前和围绝经期妇女提供了多达4次年度研究访问的数据。我们量化了9种单独的尿邻苯二甲酸酯代谢物和5种汇总措施(例如，塑料中的邻苯二甲酸酯(∑塑料))，使用汇集的年度尿液样本。我们测量了血清雌二醇，睾丸激素，每次研究访视时收集的孕酮，与月经周期无关。线性混合效应模型和分层贝叶斯核机回归分析纵向评估了个体和邻苯二甲酸酯混合物与性类固醇激素之间的调整关联。
结果：我们观察到某些邻苯二甲酸酯代谢物浓度升高与睾酮水平降低和亚排卵孕酮水平升高之间的关联，例如，邻苯二甲酸单乙酯（MEP），邻苯二甲酸单苄基酯（MBzP），邻苯二甲酸二-2-乙基己酯(∑DEHP)代谢物，∑塑料，和∑邻苯二甲酸酯浓度与较低的睾酮(例如，对于∑DEHP：-4.51%；95%CI：-6.72%，-2.26%）。对于MEP的每加倍，某些DEHP代谢物，和总结措施，我们观察到较高的平均亚排卵孕酮(例如，∑AA(具有抗雄激素活性的代谢物):6.88%;95%CI:1.94%,12.1%）。总体随时间变化的邻苯二甲酸酯混合物的较高水平与较低的雌二醇和较高的孕酮水平有关，尤其是第二年暴露。
结论：在绝经过渡期，邻苯二甲酸盐与性激素水平纵向相关。未来的研究应该评估这种关联和潜在的健康影响在这一研究的时期。
方法：来自中年妇女健康研究（MWHS）（n=751）的绝经前和围绝经期妇女提供了多达4次年度研究访问的数据。我们量化了9种单独的尿邻苯二甲酸酯代谢物和5种汇总措施(例如，塑料中的邻苯二甲酸酯(∑塑料))，使用汇集的年度尿液样本。我们测量了血清雌二醇，睾丸激素，每次研究访视时收集的孕酮，与月经周期无关。线性混合效应模型和分层贝叶斯核机回归分析纵向评估了个体和邻苯二甲酸酯混合物与性类固醇激素之间的调整关联。
结果：我们观察到某些邻苯二甲酸酯代谢物浓度升高与睾酮水平降低和亚排卵孕酮水平升高之间的关联，例如，邻苯二甲酸单乙酯（MEP），邻苯二甲酸单苄基酯（MBzP），邻苯二甲酸二-2-乙基己酯(∑DEHP)代谢物，∑塑料，和∑邻苯二甲酸酯浓度与较低的睾酮(例如，对于∑DEHP：-4.51%；95%CI：-6.72%，-2.26%）。对于MEP的每加倍，某些DEHP代谢物，和总结措施，我们观察到较高的平均亚排卵孕酮(例如，∑AA(具有抗雄激素活性的代谢物):6.88%;95%CI:1.94%,12.1%）。总体随时间变化的邻苯二甲酸酯混合物的较高水平与较低的雌二醇和较高的孕酮水平有关，尤其是第二年暴露。
结论：在绝经过渡期，邻苯二甲酸盐与性激素水平纵向相关。未来的研究应该评估这种关联和潜在的健康影响在这一研究的时期。
