Association of Exposure to Phthalate Metabolites With Sex Hormones, Obesity, and Metabolic Syndrome in US Women

Abstract

ImportanceObesity 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresUrinary 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.Main Outcomes and MeasuresSerum 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.ResultsAmong 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.Conclusions and RelevanceIn this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.

Association of heavy menstrual bleeding with cardiovascular diseases in US female hospitalizations

“…8,10,37 In addition, reduction of environmental exposure is also useful for minimizing risk of menstrual disorders and CVD events. 3,38 A higher prevalence of HMB has been reported in women with congenital cardiovascular events. 39,40 In our study, the association remained consistent between HMB and CVD outcomes even after excluding congenital cardiovascular events.…”

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

“…The population was divided into three subgroups based on body mass index (BMI): BMI of less than 25 were 'Normal weight', between 25 and 30 were 'Overweight', greater than or equal to 30 were defined as 'Obese'. PAEs metabolite levels were derived from urine samples, to control for the interference of renal metabolic differences in different individuals in the study, urinary creatinine levels were adjusted to accommodate variations in urine dilution (36,38,39), and the timing of blood sample collection was regulated to address diurnal fluctuations in sex hormone concentrations (36). For continuous variables, skewness and kurtosis tests were used to test whether the distribution of the data was approximately normal, and non-normal continuous variables were described using the median (IQR).…”

“…The reproductive toxicity of PAEs, as confirmed by numerous existing studies, encompasses adverse effects on the HPG axis, including abnormal release of gonadotropin-releasing hormone and gonadotropins, along with dysfunction of sex hormone receptors and steroid hormone synthesis (23). These factors collectively contribute to a heightened prevalence of metabolic disorders (38,51). Additionally, some researchers contend that obesity, on the contrary, heightens the risk of sex hormone imbalances (52).…”

Impact of Microplastics on the Ocular Surface

“…Phthalates are esters of phthalic acid (1,2-benzene dicarboxylic acid) used to produce polyvinyl chloride (PVC). Epidemiological studies have identified phthalates as key culprits of suppressed reproductive hormones, altered thyroid function, and the development of obesity and metabolic syndrome [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. Exposure of human corneal endothelial cells (B4G12 cell line) to phthalates increased the production of IL-1β, IL-6, and IL-8, manifesting as decreased cell proliferation and subsequent cell toxicity [ 69 ].…”