Department of Obstetrics and Gynecology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso.
Office of Research, Biostatistics and Epidemiology Consulting Lab, Texas Tech University Health Sciences Center, El Paso.
JAMA Netw Open. 2022 Sep 1;5(9):e2233088. doi: 10.1001/jamanetworkopen.2022.33088.
Obesity and metabolic syndrome are highly prevalent among the US population and are associated with the dysregulation of sex hormones. An increase in obesity and metabolic syndrome may also be associated with exposure to phthalates. The association of exposure to phthalate metabolites with sex hormones and metabolic health has been understudied in the female population.
To evaluate the association between exposure to common phthalate metabolites with total testosterone (TT) levels, sex hormone-binding globulin (SHBG) levels, obesity, and metabolic syndrome among women.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data collected from the National Health and Nutrition Examination Survey during 2013 to 2016. Female participants aged 15 years or older with urinary profiles containing common phthalate metabolites were included in this study. Statistical analyses were performed from March 15, 2021, to April 30, 2022.
Urinary concentrations of phthalate metabolites were classified into tertiles, and the lowest tertile was used as a reference category. The concentrations of phthalate metabolites and their composite scores based on clustering were also used in the analysis.
Serum concentrations of TT and SHBG were dichotomized into high TT levels (>46 ng/dL [to convert to nanomoles per liter, multiply by 0.0347] for age <50 years and >32 ng/dL for age ≥50 years) and low SHBG levels (<2.85 μg/mL [to convert to nanomoles per liter, multiply by 10.53]) as established for the female population. Obesity was defined as a body mass index of 30 or more (calculated as weight in kilograms divided by height in meters squared), and metabolic syndrome was defined using the National Cholesterol Education Program criteria. The serum concentrations of TT and SHBG were also included in the validation analyses. Modified Poisson models were used to estimate the adjusted relative risk (RR) with 95% CIs for the associations.
Among the 2004 women included in this study, the mean (SD) age was 46.6 (18.5) years (14.7% Hispanic participants, 62.7% non-Hispanic White participants, and 13.2% non-Hispanic Black participants; 17.4% of participants were born outside the US [weighted percentages]; 230 (11.8%) had high TT levels, 210 (10.4%) had low SHBG levels, 825 (39.8%) had obesity, and 965 (45.5%) had metabolic syndrome (weighted percentages). Of the 13 phthalate metabolites, 8 had the highest tertile level greater than 6.2 ng/mL (range, 0.5-75.2 ng/mL). High levels of exposure to mono(2-ethyl-5-carboxypentyl) phthalate (RR, 1.84 [95% CI, 1.33-2.54]), mono(2-ethyl-5-oxohexyl) phthalate (RR, 1.77 [95% CI, 1.21-2.59]), mono(2-ethyl-5-hydroxyhexyl) phthalate (RR, 1.94 [95% CI, 1.34-2.81]), and monobenzyl phthalate (RR, 1.75 [95% CI, 1.21-2.54]) were associated with low SHBG levels but not with high TT levels. High levels of exposure to some of these metabolites were also associated with obesity and metabolic syndrome. Most associations were specific to premenopausal or postmenopausal women.
In this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.
肥胖和代谢综合征在美国人群中非常普遍，与性激素的失调有关。肥胖和代谢综合征的增加也可能与邻苯二甲酸酯的暴露有关。邻苯二甲酸酯代谢物与女性性激素和代谢健康之间的关联在女性人群中研究较少。
评估常见邻苯二甲酸酯代谢物暴露与女性总睾酮 (TT) 水平、性激素结合球蛋白 (SHBG) 水平、肥胖和代谢综合征之间的关系。
设计、地点和参与者：这项横断面研究使用了 2013 年至 2016 年期间全国健康和营养检查调查的数据。纳入了尿液中含有常见邻苯二甲酸酯代谢物的 15 岁及以上女性参与者。统计分析于 2021 年 3 月 15 日至 2022 年 4 月 30 日进行。
邻苯二甲酸酯代谢物的尿浓度分为三分位，最低三分位用作参考类别。邻苯二甲酸酯代谢物的浓度及其基于聚类的复合分数也用于分析。
TT 和 SHBG 的血清浓度分为高 TT 水平（年龄 <50 岁时>46ng/dL[转换为纳摩尔/升，乘以 0.0347]，年龄≥50 岁时>32ng/dL）和低 SHBG 水平（<2.85μg/mL[转换为纳摩尔/升，乘以 10.53]），这是为女性人群确定的。肥胖定义为体重指数为 30 或更高（计算方法为体重以千克为单位除以身高以米为单位的平方），代谢综合征采用国家胆固醇教育计划标准定义。TT 和 SHBG 的血清浓度也包含在验证分析中。使用修正泊松模型估计关联的调整相对风险（RR）及其 95%置信区间。
在这项包括 2004 名女性的研究中，平均（标准差）年龄为 46.6（18.5）岁（14.7%西班牙裔参与者、62.7%非西班牙裔白种人参与者和 13.2%非西班牙裔黑人参与者；17.4%的参与者出生在美国境外[加权百分比]）；230 名（11.8%）女性 TT 水平较高，210 名（10.4%）女性 SHBG 水平较低，825 名（39.8%）女性肥胖，965 名（45.5%）女性代谢综合征（加权百分比）。在 13 种邻苯二甲酸酯代谢物中，有 8 种代谢物的最高三分位水平大于 6.2ng/mL（范围 0.5-75.2ng/mL）。单（2-乙基-5-羧基戊基）邻苯二甲酸酯（RR，1.84[95%CI，1.33-2.54]）、单（2-乙基-5-氧代己基）邻苯二甲酸酯（RR，1.77[95%CI，1.21-2.59]）、单（2-乙基-5-羟基己基）邻苯二甲酸酯（RR，1.94[95%CI，1.34-2.81]）和单苄基邻苯二甲酸酯（RR，1.75[95%CI，1.21-2.54]）的高水平暴露与 SHBG 水平较低有关，但与 TT 水平较高无关。这些代谢物的某些高水平暴露也与肥胖和代谢综合征有关。大多数关联仅与绝经前或绝经后妇女有关。
在这项横断面研究中，某些邻苯二甲酸酯代谢物的暴露可能与 SHBG 水平降低、肥胖和代谢综合征有关，具体取决于绝经状态。
