A cross-sectional study of phthalate exposure and correlation with testosterone and sex hormone-binding globulin (SHBG) in females in the United States of America (USA).
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Lipid-based chemicals that are added to plastic materials to increase their functionality, phthalates are diesters of orthophthalic acid that contaminate various levels of the environment. Human phthalate toxicity is best recorded as endocrine disrupting chemicals, anatomical and physiological risks to a fetus, and disturbance to musculoskeletal, dermatologic, and reproductive systems. Testosterone and sex-hormone binding globulin (SHBG) are essential components for the regulation of the reproductive system, and dysregulation can result in decreased libido, anovulation, infertility, or effect on peripheral systems. The purpose of this study was to examine the correlation of urinary phthalate metabolites with abnormal testosterone and SHBG levels in the US female population aged 15-55 years. This study examines the correlation between urinary phthalate exposure and serum female hormone levels using data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES). Weighted complex logistic regression analysis was conducted to assess the relationship between urinary creatinine-standardized phthalate concentrations and infertility status, as determined by serum testosterone and SHBG in females aged 15-55 years (N = 4,411). Subject demographic characteristics and medical and reproductive health conditions were included in the model as covariates. Among 4,411 study participants, the overall rate of infertility based on the testosterone (normal range: 15-70 ng/dl) was 24.2% (testosterone < 15: 22.4% and testosterone > 70: 1.8%) and rate of infertility based on the SHBG levels (normal range: 17.4-52.1 nmol/L) was 62.2% (SHBG < 17.4: 2.3% and SHBG > 52.1: 59.9%). Abnormal levels of testosterone were associated with increasing Mono-isononyl phthalate (MNP) [odds ratio (OR) = 1.041, 95% CI = 1.008, 1.075] and Cyclohexane 1,2-dicarboxylic acid monohydroxy isononyl ester (MHNCH) [OR = 1.030, 95% CI = 1.005, 1.055]. In the regression model for quantitative measures of SHBG, decreased SHBG levels were significantly associated with increased Mono(carboxyisononyl) phthalate (MCNP) (p = 0.034) and MHNCH (p = 0.002). Additionally, age, race, and BMI were significant predictors of female infertility in relation to SHBG levels. Analysis observed statistically significant correlation between testosterone-MNP, testosterone-MHNHC, SHBG-MCNP, and SHBG-MHNHC. Demographic factors associated with abnormal testosterone included age, country of birth, and alcohol use, and those associated with abnormal SHBG included age, education level, country of birth, body mass index (BMI), income status (FIPR), alcohol use, first menstrual cycle, and uterine cancer diagnosis. Further studies will be needed to determine causation and the mechanism of how phthalates affect testosterone and SHBG levels in females.