Table 3.
Major studies depicting associations between endocrine disruptors and obesity.
| Author, Year | Study Design/Population | Main Findings | Comments |
|---|---|---|---|
| Bisphenol A and obesity | |||
| Lin et al. (2023) [178] | Umbrella review of systematic reviews with meta-analyses on the association of BPA exposure with multiple outcomes, including obesity | - Higher BPA exposure significantly associated with obesity risk in both sexes (females: OR 1.51; males: OR 1.88) - Significant associations with generalized and abdominal obesity (OR 1.22 and 1.41, respectively) as well as overweight in adults (OR 1.25) - Significantly increased risk for type 2 DM (OR 1.28) |
Higher BPA exposure associated with obesity in children and adults, with less heterogeneity among studies in females |
| Deodati et al. (2023) [179] | Case–control study among n = 122 children (n = 66 and n = 56 with and without obesity, respectively) matched for age and gender | - Significantly higher creatinine-adjusted urinary BPA concentrations in obesity than normal weight (10.77 vs. 5.50 µg/g, respectively) among girls, but not boys. - Significantly higher risk of obesity in children with BPA levels above the median eating packaged food (OR = 11.09) |
Potential gender-specific relationship between BPA exposure and higher odds of childhood obesity in girls |
| Chen M et al. (2023) [180] | Cross-sectional study among n = 426 children aged 7 years old | - Urinary concentrations of BPA substitutes BPS, BPAF exhibit a significant positive association with BMI, WC, overweight/obesity only among boys - No associations between adiposity measures and BPA or other substitute compounds |
Associations between BPS, BPAF, but not BPA exposure and obesity in boys |
| Bi J et al. (2022) [181] | Prospective observational study including n = 796 individuals with normal weight, among whom 133 developed overweight or obesity during follow-up | - Presence of a statistically significant inverted U-shaped relationship between serum BPA and incident overweight/obesity - Significant positive correlation between log10-BPA and increase in waist-to-hip ratio - Serum adiponectin mediates 46% of association between BPA and incident overweight/obesity |
Non-monotonic relationship between baseline BPA and incident overweight/obesity among individuals with normal weight, potentially indirectly mediated by adiponectin |
| Choi et al. (2022) [182] | Cross-sectional study including 1046 adult participants in NHANES (2013–2016) and 3268 adult participants of the Korean National Environmental Health Survey (2015–2017) | Those in the higher urinary BPA tertiles had significantly higher odds for obesity (OR = 1.58 and 1.41 for 3rd and 2nd vs. 1st tertile, respectively) Similar associations for urinary BPF and BPS |
Exposure not only to BPA but also to substitutes BPF and BPS is associated with adult obesity |
| Gajjar et al. (2021) [183] | Prospective observational cohort of n = 212 children with urinary BPA and BPS measurements at 8 years and body composition assessments at 8 years (bioimpedance) and 12 years (DXA) | No evidence for a synchronous or prospective association of urinary BPA or BPS with increased adiposity | |
| Wu et al. (2020) [184] | Cross-sectional study including n = 2372 children and adolescents (aged 6–19) participating in NHANES | BPA levels significantly associated with higher weight in a statistical approach implementing weighted quantile sum statistical model but not in other approaches | Evidence for an association between BPA exposure and childhood/adolescent obesity |
| Ribeiro et al. (2020) [185] | Meta-analysis of studies investigating BPA exposure and multiple adverse health outcomes, including obesity | - BPA is significantly associated with overweight (OR 1.254), obesity (OR 1.503) and increased WC (OR 1.503) in adults - OR 1.8 for childhood obesity |
Positive association between BPA exposure and generalized as well as abdominal obesity |
| Wu et al. (2020) [186] | Meta-analysis of 10 observational studies | - Statistically significant dose–response positive relationship between BPA and overweight/obesity risk in both sexes - 11% increase in obesity risk for every 1 ng/mL of BPA |
Continuous positive relationship between BPA and obesity irrespective of sex |
| Jacobson et al. (2019) [187] | Cross-sectional study including n = 1831 children and adolescents (aged 6–19) participating in NHANES | Urinary BPS and BPF but not total bisphenols or BPA were significantly associated with, particularly abdominal obesity | Substitute bisphenol exposure may predispose individuals to childhood/adolescent obesity |
| Liu et al. (2019) [188] | Cross-sectional study including n = 745 children and adolescents (aged 6–17 years) participating in NHANES | Urinary BPA (OR 1.74) and BPF (OR 1.54) are significantly associated with obesity, with stronger associations between boys Similar findings for abdominal obesity |
Urinary BPA and its substitute BPF associated with obesity, particularly in boys |
| Zhang et al. (2019) [189] | Cross-sectional study including n = 1269 adults participating in NHANES | Among other chemicals, increased urinary BPA and BPS are significantly associated with higher obesity prevalence | Exposure to BPA, and BPS may predispose individuals to adulthood obesity, although the authors recommend considering the joint effects of different chemical exposures |
| Hao et al. (2018) [190] | Prospective study (mean follow-up: 4 years) among 888 Chinese adults without abdominal obesity at baseline | OR = 2.30 for incident abdominal obesity each unit increase in log [BPA] urinary concentration after adjustment for confounding factors Individuals in the lowest tertile of BPA concentrations had the lowest risk for incident central obesity (ORs 1.73 and 1.81 for those in the 2nd and 3rd tertiles, respectively) |
Prospective association of BPA exposure with incident central obesity in Chinese adults |
| Do et al. (2017) [191] | Cross-sectional analysis of data from n = 4733 adults aged (18 to 79 years) | For each natural-log unit increase in urinary BPA concentration, significant increase of 0.33 kg/m2 in BMI and 1.00 cm in waist circumference | Dose–response relationship between BPA exposure and generalized as well as abdominal obesity |
| Song et al. (2014) [192] | Prospective (10 years) cohort study of 977 women with baseline measurements of urinary BPA and 9 phthalate biomarkers | After adjustment for dietary and lifestyle variables, those in the highest BPA quartile gained on average an additional 0.23 kg/year (0.07–0.38) of body weight during follow-up | BPA exposure is associated with greater longitudinal weight gain in women |
| Bhandari et al. (2013) [193] | Cross-sectional analysis of data from n = 2200 children and adolescents (aged 6 to 18 years) from NHANES (2003–2008) | - OR for obesity = 2.55 for children in the highest vs. lowest quartile of urinary BPA - Associations more robust among males and non-Hispanic Whites |
BPA is associated with childhood/adolescent obesity, with potential gender- and race-specific effects |
| Shankar et al. (2012) [194] | Cross-sectional analysis of data from n = 3967 adult participants in NHANES (2003–2008) | ORs = 1.69 and 1.59 for generalized and abdominal obesity for the 4th vs. 1st quartile of urinary BPA concentrations, persistent after adjustment for several confounders and consistent among gender and race–ethnic groups | BPA exposure is associated with central and abdominal obesity in both genders and all race groups, irrespectively of traditional risk factors |
| Trasande et al. (2012) [195] | Cross-sectional analysis of data from n = of 2838 children and adolescents (aged 6–19 years) participating in NHANES | - Lowest prevalence of obesity in the 1st vs. 2nd-4th quartiles of ascending urinary BPA concentrations (10.3% vs. 20.1%, 19.0% and 22.3%, respectively) - Association of BPA and obesity significant in Whites but not Blacks or Hispanics |
Association between BPA exposure and obesity likely exhibits race-specific effects |
| Wang et al. (2012) [196] | Cross-sectional study of n = 3390, aged >40 years | - Those in the highest quartile of urinary BPA concentrations showed significantly higher prevalence of generalized (OR = 1.50) and abdominal obesity (OR = 1.28) - Among participants without overweight or obesity, higher BPA was significantly associated with IR (OR 1.94) |
Evidence for a positive association between BPA exposure and obesity, as well as IR among lean individuals |
| Carwile et al. (2011) [197] | Cross-sectional study including n = 2747 adults (aged 18–74) participating in NHANES (2003–2006) | Higher risk of general (OR 1.74) and abdominal (OR 1.58) obesity among individuals in the highest vs. lowest quartile of urinary BPA concentration | BPA exposure is associated with general and abdominal obesity in US adults |
| Phthalates and obesity | |||
| Deodati et al. (2023) [179] | Case–control study among n = 122 children (n = 66 and n = 56 with and without obesity, respectively) matched for age and gender | - Early downstream metabolites of Di(2-ethylhexyl) phthalate in urine significantly higher in girls with obesity than normal weight - Significant positive correlation of Di(2-ethylhexyl) phthalate metabolites with serum leptin levels |
Significant correlation of certain phthalate metabolites with increased adiposity in girls |
| Stevens DR et al. (2023) [198] | Prospective study among n = 438 infants from the Healthy Start prospective pregnancy cohort. | - Significant inverse association between maternal urinary mono-benzyl and di- n-butyl phthalate at 28th gestational week and percentage fat mass at birth in male infants |
Maternal phthalate exposure in pregnancy is inversely associated with fat mass in male, but not female, infants at birth |
| Li et al. (2023) [199] | Case–control study among n = 240 children with overweight/obesity (OBE) and n = 240 age- and gender-matched controls | Among 9 phthalates, monomethyl phthalate and monobutyl phthalate were significantly higher in controls than children with overweight/obesity but not after adjustment for physical activity and caloric intake. | No significant differences in phthalate concentrations between OBE and controls |
| Wu et al. (2022) [200] | Meta-analysis of observational studies for the association between phthalate compounds and obesity in adult and pediatric populations | - Mono-n-butyl-, monobutyl-, monoisobutyl-, monoethyl- and mono(2-ethyl-5-carboxypentyl) phthalate significantly associated with obesity, specific compounds more strongly correlate with general or abdominal obesity - Stronger associations in women and in studies from the United States and Europe |
Compound-specific effects on general and abdominal obesity, with potential gender- and study-site-specific effects |
| Boyer et al. (2023) [201] | Measurement of the concentrations of 9 phthalates in n = 379 pregnant women, in relation to gestational weight gain (difference between pre-pregnancy and median 35.1 weeks weight) | Significant direct association between mono-(3-carboxypropyl) phthalate and mono-n-butyl phthalate was positively associated with gestational weight gain (1.81 kg and 0.77 kg at 35 weeks) interquartile range increase among women with obesity | Phthalate exposure is associated with greater weight gain in pregnancy, particularly among women with obesity at baseline |
| Vieyra et al. (2023) [202] | Prospective observational study n = 1125 participants of the Woman Health Initiative (WHI) with available urine phthalate measurements and DXA-based estimations of VAT and SAT | Significant positive associations of baseline di-isobutyl phthalate biomarkers, monocarboxy-isononly phthalate, and di(2-ethylhexyl) phthalate with VAT three years later, which persisted after adjustment for SAT | Higher levels of certain urinary phthalate compounds are longitudinally associated with higher VAT over time in postmenopausal women |
| Milankov et al. (2023) [203] | Cross-sectional study among n = 60 women with PCOS | Total urinary phthalate concentrations significantly positively correlate with BMI, waist circumference, waist-to-height ratio, VAI, FPG and HOMA-R | Increased phthalate exposure associated with obesity, insulin resistance and hyperglycemia in women with PCOS |
| Wang et al. (2023) [204] | Cross-sectional study among n = 798 students (7–10 years) | Significantly increased risk of abdominal obesity for the fourth vs. first quartile (OR = 5.29 and 3.73) and 273% (OR = 3.73; 95% CI: 1.57, 8.86) of urinary concentrations of monoethyl phthalate and monoisobutyl phthalate | Monoethyl-phthalate and monoisobutyl-phthalate exposure are associated with abdominal obesity in children |
| Peng et al. (2023) [205] | Prospective observational analysis of n = 1369 women in the Study of Women’s Health Across the Nation Multi-Pollutant Study | Significantly higher levels of spot urinary phthalates (except mono-carboxy-isononyl phthalate) were associated with faster increases in body fat percentage and fat mass, but not total body weight change over time | Urinary phthalate concentrations positively correlated with fat gain in middle-aged women |
| Kupsko et al. (2022) [206] | Prospective observational study of 514 mother–child pairs in pregnancy until twelve years post-term | Higher maternal urine di (2-ethylhexyl) phthalate metabolites significantly associated with greater odds of high and increasing weight in infants Higher di-isononyl phthalate metabolites significantly associated with greater odds increasing weight in infants |
Exposure to certain phthalates during pregnancy exerts a significant impact in infant weight trajectories during childhood |
| Ribeiro et al. (2019) [207] | Meta-analysis of 29 studies for the association between phthalate compounds and obesity in adult and pediatric populations | - The low number of studies for many phthalate compounds precludes meta-analysis - Statistically significant association solely between mono(2-ethyl-5-carboxypentyl) phthalate and obesity in adults (OR = 1.67) |
Positive association between many phthalate compounds and adiposity measures, most formally non-significant; possible publication-bias-related effects |
| Díaz Santana et al. (2019) [208] | Cross-sectional (n = 997) and prospective (n = 660) observational study among participants of the Woman Health Initiative (WHI) | - Significant positive associations between urinary phthalate biomarker concentrations and obesity in cross-sectional analysis - Baseline urinary mono-(2-ethyl-5-oxohexyl)-, monoethyl-, mono-hydroxybutyl- and mono-hydroxyisobutyl phthalate significantly correlate with weight gain after 3 years - No associations with weight changes at 6 years |
Exposure to certain phthalates may predispose individuals to obesity and short-term weight gain |
| Rodriguez-Carmona, et al. (2019) [209] | Prospective cohort study among n = 178 pregnant women | Higher urinary mono-3-carboxypropyl pthalate is significantly associated with moderately increased weight gain over the next 5.2–10.7 years Higher mono-benzyl phthalate significantly associated with lower weight gain in the same timeframe |
Prospective association between phthalate exposure in pregnancy and prospective weight changes in women |
| Buckley et al. (2016) [210] | Prospective cohort study assessing the fat mass of n = 180 children (4–9 years) in relation to maternal third-trimester urinary phthalate concentrations in pregnancy | - No continuous associations between maternal urinary phthalate concentrations and fat mass in offspring, without apparent gender-specific effects - 3.06% lower fat mass in children in the highest vs. lowest quartile of summed di(2-ethylhexyl) phthalate metabolites |
No evidence for an impact of maternal phthalate exposure and increased infantile fat mass |
| Valvi et al. (2015) [211] | Prospective cohort study of n = 391 mothers with creatinine-adjusted measurements of urinary phthalates in the 1st and 3rd trimesters of pregnancy | High-molecular-weight phthalate metabolites in maternal urine significantly associated with lower BMI z-scores in boys and higher in girls 4–7 years of age | Potential gender-specific effects of maternal phthalate exposure and infantile BMI trajectories |
| Yaghjyan et al. (2015) [212] | Cross-sectional analysis including n = 6005 women without diabetes participating in NHANES (1999–2004) | - Significant positive associations between monobutylphthalate, mono-2-ethylhexyl- to mono(2-ethyl-5-hydroxyhexyl) phthalate ratio and BMI, WC | Among the observed associations, the higher mono-2-ethylhexyl- to mono(2-ethyl-5-hydroxyhexyl) phthalate ratio may be reflective of slower oxidative metabolism of mono-2-ethylhexyl-pthalate |
| Song et al. (2014) [192] | Prospective cohort study of n = 977 women with baseline measurements of urinary BPA and 9 phthalate biomarkers | After adjustment for dietary and lifestyle variables, significant albeit moderate positive dose–response relationship between phthalic acid, monobenzyl- and monobutyl-phthalate and weight gain over 10 years | Exposure to certain phthalates is associated with accelerated weight gain in women |
| Lind et al. (2012) [213] | Prospective cohort study among n = 1016 individuals of 70 years of age | Baseline serum concentrations of mono-isobutyl phthalate and mono-methyl phthalate significantly positively associated with DXA- and abdominal MRI-derived indices of adiposity in women two years later, but not in men | Circulating concentrations of certain phthalates are associated with increased adiposity only in women, suggesting possible sex-specific associations of phthalates with obesity |
| Hatch et al. (2008) [214] | Cross-sectional analysis of data of n = 4369 NHANES participants (1999–2002) | - Positive trends of BMI and WC across quartiles of concentrations of mono-benzyl, mono-2-ethyl-5-oxohexyl, mono-ethyl, mono-n-butyl, mono-2-ethyl-5-hydroxyhexyl, particularly among males 20–59 years old - Similar trends across mono-ethyl phthalate quartiles in adolescent girls, less strong in adult women - Inverse trend for mono-2-ethylhexyl phthalate in adolescent girls and several inverse associations in adults 60–80 years - No associations in children |
Exposure to several phthalates may be associated with increased adiposity, but age-group- and gender-specific effects likely exist |
| Stahlhut et al. (2007) [78] | Cross-sectional analysis of data of n = 1443 men participating in NHANES (1999–2002) | - Urinary concentrations of monobenzylphthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate and monoethylphthalate are significantly associated with increased waist circumference, after adjustment for confounders - Monobutylphthalate, monobenzylphthalate and monoethylphthalate concentrations exhibit significant positive correlations with HOMA-R |
Exposure to certain phthalates is associated with higher abdominal obesity and insulin resistance |
Abbreviations: BMI: body mass index; BPA/BPF/BPS: bisphenol A, F and S; DXA: dual X-ray absorptiometry; FPG: fasting plasma glucose; HOMA-R: Homeostatic Model Assessment for Insulin Resistance; NHANES: National Health and Nutrition Examination Survey; PCOS: polycystic ovary syndrome; SAT: subcutaneous adipose tissue; VAI: visceral adiposity index; VAT: visceral adipose tissue, WC: waist circumference.