Phthalates and Sex Steroid Hormones Among Men From NHANES, 2013–2016

Abstract

Context Phthalates are commonly found in commercial packaging, solvents, vinyl, and personal care products, and there is concern for potential endocrine-disrupting effects in males. The commonly used di-2-ethylhexyl phthalate (DEHP) has progressively been replaced by seldom studied compounds, such as bis-2-ethylhexyl terephthalate and 1,2-cyclohexane dicarboxylic acid di-isononyl ester (DINCH). Objective To investigate the associations between the urinary phthalate metabolites and serum sex steroid hormone concentrations in a nationally representative sample of adult males. Design, Setting, Participants, and Intervention This was a cross-sectional analysis of data from the 2013–2016 National Health and Nutrition Examination Survey among 1420 male participants aged ≥20 years. Main Outcome Measures Serum levels of total testosterone, estradiol, SHBG, and derived sex hormone measurements of free testosterone, bioavailable testosterone, and free androgen index were examined as log-transformed continuous variables. Results Phthalate metabolites were not statistically significantly associated with sex hormone concentrations among all men. However, associations varied by age. High molecular weight phthalates were associated with lower total, free, and bioavailable testosterone among men age ≥60. Specifically, each doubling of ΣDEHP was associated with 7.72% lower total testosterone among older men (95% confidence interval, -12.76% to -2.39%). Low molecular phthalates were associated with lower total, free, and bioavailable testosterone among men age 20 to 39 and ∑DINCH was associated with lower total testosterone among men age ≥40. Conclusions Our results indicate that males may be vulnerable to different phthalate metabolites in age-specific ways. These results support further investigation into the endocrine-disrupting effects of phthalates.

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

“…Similarly, in men with benign prostatic hyperplasia, estradiol levels, testosterone and steroidogenic enzymes aromatase, and 5α-reductase were increased [ 107 ]. Other studies observed associations between postnatal exposure to phthalates in healthy and infertile men and decreased testosterone [ 80 , 194 , 195 , 196 , 197 , 198 ]. Epidemiological studies yielded some conflicting results in the association between phthalate exposure and estradiol levels in men.…”

Comprehensive Insight from Phthalates Occurrence: From Health Outcomes to Emerging Analytical Approaches

“…Many phthalates, even at a low concentration, are known endocrine disruptors ( Figure 3 ) that have an influence on the development of organisms and their reproductive system [ 33 ]. For instance, PAEs have been recognized to induce changes in oxidative stress, disturb sex hormone balances, which can decrease fertility and increase the rate of reproductive defects and malformations [ 33 , 34 , 35 , 36 ]. Interference with testosterone activity, especially early in life, can have irreversible effects on male reproduction [ 37 ].…”

Free testosterone and cardiometabolic parameters in men: comparison of algorithms

“…As indicated by the name, FAI is not an estimate of the free testosterone concentration but simply an index of the balance between serum testosterone and SHBG. While it is recognized that FAI is not based on any biophysical characterization, it continues to be used by investigators ( 9 , 10 ). Several algorithms based on law-of-mass-action equations requiring information on the level of TT and SHBG have been developed with varying degree of correlation with equilibrium dialysis and some have been suggested as reasonable alternatives to direct measurements ( 1 ).…”