A cross sectional study of urinary phthalates, phenols and perchlorate on thyroid hormones in US adults using structural equation models (NHANES 2007-2008)

Abstract

Background: Biomonitoring data shows that people are exposed to phthalates, phenols and perchlorates. Many of these compounds are endocrine disrupting compounds that affect thyroid hormone levels. Yet the effect of these compounds on thyroid hormone levels are often evaluated individually rather than as a mixture. Our objective was to examine the association between 11 urinary endocrine disrupting compounds and thyroid hormones using structural equation models.

Methods: Using data from the National Health and Nutrition and Examination Survey 2007-2008, we fit a latent variable utilizing urinary measurements of 9 compounds in females (perchlorate, bisphenol A, benzophenone-3, mono-2ethyl5carboxypentyl phthalate, mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono(2ethyl5hydroxyhexyl) phthalate, mono-benzyl phthalate, and mono-isobutyl phthalate) and 8 compounds in males (without benzophenone-3). The association of the latent variable with serum thyroid hormones (Total T3, Total T4, and Thyroid Stimulating Hormones) was assessed in females (N = 710) and males (N = 850) over the age of 12 controlling for age, race, and urinary creatinine.

Results: In males, urinary endocrine disrupting compound levels were negatively associated with thyroxine (β: -0.19, 95% Confidence Interval (95% CI): -0.31, -0.05). In females, urinary endocrine disrupting compound levels were positively associated with triiodothyronine serum concentrations (β: 0.09, 95% CI: -0.03, 0.21) however this association was not statistically significant.

Conclusions: This cross-sectional analysis provides additional evidence that environmental exposure to phthalates and phenols is associated with endocrine-related processes. Furthermore, these results suggested sex-specific differences in exposure to endocrine disrupting mixtures, and the exposure-response between endocrine disrupting mixtures and thyroid hormone levels. Specifically, higher exposure to a mixture of endocrine disrupting compounds was associated with lower levels of total T4 in males but not in females. While a structural methodological framework was used to assess these complex relationships, the cross sectional nature of this analysis limits causal inference and further research is needed to determine the clinical significance of these findings.

Keywords: EDCs; Endocrine disrupting compounds; Structural equation modeling; Thyroid hormones.

Figure 1.

Relationship between the hypothalamic-pituitary-thyroid axis and EDCs. EDCs can disrupt the axis and influence thyroid homeostasis by (a) binding to transport molecules, (b) binding to receptors, (c) mimicking THs, and (d) blocking iodine from entering the thyroid.

Figure 2.

A priori model of relationship between 11 EDC compounds and THs after adjustment for creatinine. The latent Exposure variable represent exposure to a mixture of EDCs. Perchlorate is represented by “Perchlor”, benzophenone-3 is represented by “Benzo”, and triclosan is represented by “Tri”, mono-2ethyl5carboxypentyl phthalate is represented by “MECPP”, mono-n-butyl phthalate is represented by “MnBP”, mono-(3-carboxypropyl) phthalate is represented by “MCPP”, mono-ethyl phthalate is represented by “MEP”, mono(2ethyl5hydroxyhexyl) phthalate is represented by “MEHHP”, mono-benzyl phthalate is represented by “MBzP”, and mono-isobutyl phthalate is represented by “MiBP”.

Figure 3.

SEM of relationship between EDC and THs in males after adjusted EDCs for creatinine, T3 for age, and TSH for Smoking Status. Not pictured: correlation between TSH and BMI.

Figure 4.

SEM of relationship between EDC and THs in females after adjusting EDCs for being Non-Hispanic Black (NHB) and T3 and TSH for age. Not pictured: correlation between T4 and BMI and correlation between BMI and benzophenone-3.