Phthalate metabolites and sex steroid hormones in relation to obesity in US adults: NHANES 2013-2016

Abstract

BackgroundObesity and metabolic syndrome pose significant health challenges in the United States (US), with connections to disruptions in sex hormone regulation. The increasing prevalence of obesity and metabolic syndrome might be associated with exposure to phthalates (PAEs). Further exploration of the impact of PAEs on obesity is crucial, particularly from a sex hormone perspective.MethodsA total of 7780 adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 were included in the study. Principal component analysis (PCA) coupled with multinomial logistic regression was employed to elucidate the association between urinary PAEs metabolite concentrations and the likelihood of obesity. Weighted quartiles sum (WQS) regression was utilized to consolidate the impact of mixed PAEs exposure on sex hormone levels (total testosterone (TT), estradiol and sex hormone-binding globulin (SHBG)). We also delved into machine learning models to accurately discern obesity status and identify the key variables contributing most to these models.ResultsPrincipal Component 1 (PC1), characterized by mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) as major contributors, exhibited a negative association with obesity. Conversely, PC2, with monocarboxyononyl phthalate (MCNP), monocarboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) as major contributors, showed a positive association with obesity. Mixed exposure to PAEs was associated with decreased TT levels and increased estradiol and SHBG. During the exploration of the interrelations among obesity, sex hormones, and PAEs, models based on Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms demonstrated the best classification efficacy. In both models, sex hormones exhibited the highest variable importance, and certain phthalate metabolites made significant contributions to the model’s performance.ConclusionsIndividuals with obesity exhibit lower levels of TT and SHBG, accompanied by elevated estradiol levels. Exposure to PAEs disrupts sex hormone levels, contributing to an increased risk of obesity in US adults. In the exploration of the interrelationships among these three factors, the RF and XGBoost algorithm models demonstrated superior performance, with sex hormones displaying higher variable importance.

Association between sex hormone binding globulin and metabolic syndrome in US adults: insights from National Health and Nutrition Examination Survey (NHANES) 2013–2016

“…Obesity and MetS represent significant health challenges in the U.S, and they are associated with disturbances in sex hormone regulation [ 8 ]. Human sex hormone-binding globulin (SHBG) is a serum protein with a strong and specific ability to bind to androgens and estrogens [ 9 ].…”

“…Research has revealed that the prevalence of low SHBG levels in the American population is 3.3% in males and 2.7% in females. Risk factors associated with low SHBG levels include elevated body mass index, diabetes, race (Hispanic, non-Hispanic black, or non-Hispanic white), chronic obstructive pulmonary disease, coronary heart disease, smoking and exposure to phthalates [ 8 , 10 ]. SHBG levels are independently associated with the risk of diabetes, dementia, non-alcoholic fatty liver disease, hypertension, coronary heart disease, and ischemic stroke [ 11 – 14 ], all of which are associated with a higher risk of MetS.…”