Table 4.
Summary of human studies on the association between bisphenols exposure and thyroid parameters.
| Study Design | Country | Study Sample | Sample Size (N) | Age | Principal Results | BPA Concentration | Confounders | Reference |
|---|---|---|---|---|---|---|---|---|
| Prospective | Japan | Women with a history of three or more (3–11) first-trimester miscarriages. Blood samples collected 5–9 days after ovulation in at least two cycles. | 45 patients | 27–36 | No difference in serum BPA levels between patients with and without hypothyroidism. Serum TSH levels not estimated. |
Patients with hypothyroidism: Mean (SD): 2.99 ± 3.04 µg/L Patients without hypothyroidism: Mean (SD): 2.50 ± 5.70 µg/L |
- | [151] |
| Prospective | Belgium | Overweight and obese individuals. Lean individuals. For obese individuals, urine samples collected at baseline, before starting a weight loss program (N = 151) and after 3 (N = 95), 6 (N = 53), 12 months (N = 39). |
151 obese individuals 43 lean individuals |
≥18 | The obese group had higher urinary levels of BPA. Positive relationship of urinary BPA with serum TSH in lean subjects. |
Obese individuals 0—median: 1.7 µg/L 3 months—median: 2.0 µg/L 6 months—median: 1.7 µg/L 12 months—median: 1.5 µg/L Lean individuals Median: 1.2 µg/L |
[1,7,34] | [152] |
| Prospective birth cohort | USA | Pregnant women from the CHAMACOS study. Urine samples collected at 12 and 26 weeks of gestation. | 476 | ≥18 | In mothers, no association of urinary BPA (average) with FT4 and TSH levels, and negative association (BPA 26 week) with serum TT4. Inverse association between maternal BPA (average, 26 week) and TSH in male newborns but not in females. | LOD: 0.4 μg/L Mothers: GM: 1.3 µg/g cr Median: 1.2 µg/g cr |
[1,2,4,8,10,12,13,14,15,16,17,18,19,20,21] | [143] |
| Prospective birth cohort | USA | Pregnant women from the HOME study. Urine samples collected at both 16 and 26 weeks of gestation (N = 237). | 249 | ≥18 | Neither association of maternal BPA (16 week) with maternal THs or TSH levels nor of maternal BPA (average, 16 week, or 26 week) with THs or TSH levels in newborns. Significant inverse association of maternal BPA with TSH levels (average and 26 week BPA) and slight positive association with TT3 levels (26 week BPA) in females. Stronger relationship of BPA–TSH among girls born from iodine-deficient mothers. | LOD: 0.4 μg/L 16 weeks GM: 2.0 (95%CI 1.8–2.2) µg/g cr 26 weeks GM: 2.3 (95%CI 2.1–2.5) µg/g cr |
[1,2,8,9,10,15,16,17,19,20,22,23,24,25] | [148] |
| Prospective birth cohort | Japan | Pregnant women at 23–35 weeks of gestation (singleton babies). Cord blood obtained at delivery. | 283 | ≥18 | No association between BPA concentration in cord blood and TSH or FT4 levels in newborns of both sexes. | LOQ: 0.04 µg/L GM: 0.051 µg/L IQR: <LOQ–0.076 µg/L |
[19,38] | [146] |
| Nested case-control | USA | Women who delivered preterm (< 37 weeks of gestation) and controls of women who delivered a singleton infant after 37 weeks of gestation. Urine samples collected at up to 4 visits (median for each visit: 9.64, 17.9, 26.0, and 35.1 weeks of gestation). |
116 cases 323 controls |
≥18 | IQR increase in BPA concentrations across study visits was significantly associated with lower TSH and higher FT4 levels. No effect on FT3, and inverse but not significant association of BPA with TT4 levels. No association of BPA with serum FT4 at visit 3. Significant inverse association of BPA with TSH levels at visits 3 and 4 and a slight increase of serum TT3 at visit 4. | Total: GM ± SD: 1.18 ± 2.82 µg/L 1 visit: GM ± SD: 1.33 ± 2.84 µg/L 2 visit: GM ± SD: 1.04 ± 2.85 µg/L 3 visit: GM ± SD: 1.22 ± 2.84 µg/L 4 visit: GM ± SD: 1.12 ± 2.70 µg/L |
[2,3,4,8,17,19,25,35,36,37], | [139] |
| Case-control | Korea | Infants with congenital hypothyroidism and their mothers; healthy infants with their mothers. Blood samples collected. |
26 congenital hypothyroidism mother–infant pairs 12 normal mother–infant pairs |
<24 months | TBBPA levels not significantly different in the two infant groups. No significant correlation between TBBPA and any of the THs levels in infants with congenital hypothyroidism. In their mothers, positive weak correlation of TBBPA with serum FT4 and thyroid stimulating immunoglobulin. |
Normal group and their mothers TBBPA mothers: 10.93 ng/g lipid TBBPA infants: 77.65 ng/g lipid Congenital hypothyroidism group and their mothers TBBPA mothers: 8.89 ng/g lipid TBBPA infants: 83.4 ng/g lipid |
[1,47,48,49] | [140] |
| Case-control | Cyprus (n = 122) Romania (n = 90) |
Females with thyroid nodules (diameter >3mm). Females without nodules. Two spot urine samples collected in Cyprus (7 day apart from each other). In Romania one spot sample collected. |
212: 106 cases 106 controls |
≥18 | In the whole study population, median TSH and BPA levels were significantly lower in the cases. Significant positive association of BPA with TSH levels and TNs. Neither association of BPA, BPF, or ClxBPA with FT4 levels nor of BPF and ClxBPA with serum TSH. No association of BPF and ClxBPA with TNs. | LOD (BPA): 10 μg/L LOD (BPF): 13 μg/L LOD (ClxBPA): 10–17 μg/L Median: BPA: 2.25 (1.10–4.61) μg/L BPF: 0.46 (0.32–0.72) μg/L ClxBPA: 0.16 (0.15–0.19) μg/L BPA Cases: 1.75 (1.11–3.56) μg/L BPA Controls: 2.71 (1.08–5.91) μg/L |
[1,3,10,11,39,40,41] | [147] |
| Case-control | Turkey | Children with HT. Children without HT. Spot urine samples collected. |
29 cases (25 females and 4 males) 29 controls |
8–16 | No significant difference in urinary BPA levels between the two groups. Significant negative correlation between BPA and FT4 levels in HT group. No correlation between urinary BPA concentration and TPOAb levels. | LOD: 0.5 ng/mL Mean (± standard error of the mean) Cases: 7.31 ± 1.46 µg/g cr Controls: 7.72 ± 1.74 µg/g cr |
- | [155] |
| Case-control | China | Women with TNs. Women without nodules. First morning urine collected. |
1416: 705 cases 711 controls |
≥18 | Urinary BPA was significantly higher in cases than in controls. Increased prevalence of TNs with increasing urinary BPA quartiles. Significant association between urinary BPA and TNs in all age groups and in the thyroid autoantibody positive group. |
LOD: 0.1 µg/L Median: Total: 3.08 (1.60–5.81) µg/g cr Cases: 3.27 (1.77–6.53) µg/g cr Controls: 2.92 (1.44–5.27) µg/g cr |
[1,3,8,10,11,29,30,31,44,45,46] | [159] |
| Multicentre, cross-sectional | Italy | Patients with TNs. Patients with DTC. Blood collected from each patient. |
27 with TNs 28 with DTC |
≥18 | Significant correlation between urinary BPAF concentration and risk of DTC in patients with TNs. BPS and BPB concentrations higher in patients with TNs, as compared with DTCs. TSH levels higher in patients with DTCs and in subjects exposed to BPE and BPA. |
Subjects with TNs (median ± SD) BPAF: 12.47 ± 0 ng BPS: 59.29 ± 50.29 ng BPB: 29.92 ± 35.60 ng Subjects with DTC (median ± SD) BPAF: 9.44 ± 5.41 ng BPS: 34.79 ± 41.86 ng BPB: 14.36 ± 15.31 ng |
[50] | [161] |
| Cross-sectional | USA | Men who are partners of subfertile couples. Single spot urine (N = 167), second (N = 75), and third (N = 4) urine samples collected. | 167 | 18–55 | Inverse relationship of BPA with TSH levels. No effects on T3 and T4 levels. |
LOD: 0.4 µg/L GM and median: 1.3 µg/L |
[1,2,3,4,5,6] | [150] |
| Cross-sectional | USA | Adult and adolescents from the NHANES 2007–2008. Single spot urine collected. | 1346 adults 329 adolescents |
≥20 12–19 |
In adults, inverse relationship of BPA with TT4 levels. Inverse trends between BPA quintiles and both TT4 and TSH. | GM: 2.03 µg/g cr GM: 1.88 µg/g cr |
[1,2,3,7,8,9,10] | [145] |
| Cross-sectional | USA | Adults and adolescents from the NHANES 2007–2008. Urine sample collected. | 710 females; 850 males | 12–85 | Negative association between urinary multiple EDCs including BPA and TT4 levels in males but not in females. Positive but not statically significant association of EDCs with T3 levels in females. | LOD (BPA): 0.13 µg/L Males: GM: 2.19 (95% CI 1.94–2.47) µg/L Females: GM: 2.00 (95% CI 1.80–2.23) µg/L |
[1,2,4,9,10,11,26] | [142] |
| Cross-sectional | China | Workers in two semiautomatic epoxy resin factories. Spot urine collected at the end of the shift on Friday. | 28 (21 males and 7 females) |
22–62 | The workers with the highest BPA concentrations (feeding position) had higher FT3, TT3, TT4 levels, and lower TSH levels. Urinary BPA significantly associated with higher FT3 levels (when office workers were excluded). Weak positive association between BPA and serum FT4. |
Total workers: GM ± SD: 31.96 ± 4.42 μg/g cr Feeding operators: GM ± SD: 192.45 ± 2.78 μg/g cr Crushing and packing: GM ± SD: 17.08 ± 2.33 μg/g cr Office workers: GM ± SD: 11.60 ± 1.70 μg/g cr |
[11] | [141] |
| Cross-sectional | China | Population-based study. Spot morning urine collected. |
3394: 1354 males 2040 females |
≥40 | Significant positive association of urinary BPA with serum FT3 and inverse association with TSH levels both in men and in women. Positive association between high thyroid function and high urinary BPA levels. |
LOD: 0.3 μg/L Median: 0.81 µg/L IQR: 0.47–1.43 µg/L Overt and subclinical hypothyroidism subjects: GM: 0.63 (95% CI 0.52–0.77) µg/L Euthyroid subjects: GM: 0.81 (95% CI 0.78–0.83) µg/L Overt and subclinical hypothyroidism subjects: GM: 1.05 (95% CI 0.84–1.32) µg/L |
[1,3,4,8,11,17,27] | [149] |
| Cross-sectional | China | Students of primary schools. First morning urine samples collected. | 718 | 9–11 | BPA levels similar among boys and girls but increased with age. Significant inverse association between urinary BPA and thyroid volume. Risk of TNs increased with age without any association with sex or urinary iodine level. BPA inversely associated with risk of multiple TNs. | Urinary iodine: Median: 159 μg/L Urinary BPA: Median (IQR): 2.45 (1.09–5.97) µg/g cr |
[1,3,7,11,42,43] | [158] |
| Cross-sectional | China | Patients with NG. Patients with PTC. Healthy controls. Spot blood and urine samples collected in the morning. |
53 60 65 |
≥18 | Urinary BPA and urinary iodine levels in NG and PTC groups were significantly higher than those in controls. Urinary BPA levels in the females of NG group and both the male and female PTC groups were higher than those in the control group of the same sex. Urinary BPA concentration was significantly lower in the female PTC group than in the female NG group. Urinary iodine in the PTC or NG groups was higher than that of controls of the same sex. Significant correlation between urinary BPA and iodine concentrations in all groups. |
LOQ for BPA in urine: 0.1 µg/L LOQ for BPA in serum: 0.2 µg/L LOD for iodine in urine: 3 µg/L Serum BPA GM: 7.42 (4.03–13.82) µg/L Urinary BPA: GM: 2.82 (0.016–59.78) µg/g cr Urinary iodine: GM: 335.05 (71.25–2995.74) µg/g cr BPA—Control group GM: 1.06 (0.015–27.88) µg/g cr BPA—NG group GM: 5.22 (0.022–50.78) µg/g cr BPA—PTC group GM: 4.68 (0.032–29.30) µg/g cr |
[11] | [160] |
| Cross-sectional | Thailand | Subjects from the National survey NHES 2009. Serum sample collected. | 2340 | ≥15 | Significantly inverse association of serum BPA with FT4 levels in males but not in females after exclusion subjects of thyroid autoantibodies. No association with serum TSH in both sexes. | LOD: 0.3 μg/L Median: 0.33 (0–66.91) µg/L |
[1,3,7] | [144] |
| Cross-sectional | Thailand | Subjects from the National survey NHES 2009. Serum sample collected. | 2361 | ≥15 | Significant association of increasing BPA quartiles with positivity for TgAb and TPOAb both in men and women but not for TRab. Age, sex, and BMI were independent predictors of TgAb and TPOAb positivity. | LOD: 0.3 μg/L Median: 0.32 (0–66.9) µg/L |
- | [156] |
[1]: age; [2]: race and ethnicity; [3]: BMI; [4]: smoking; [5]: timing of collection of blood/urine samples by season; [6]: timing of collection of blood/urine samples by time of day; [7]: sex; [8]: education level; [9]: serum cotinine; [10]: urinary iodine; [11]: urinary creatinine; [12]: family income; [13]: country of birth; [14]: number of years spent in the United States; [15]: parity; [16]: gestational age at the time of blood collection; [17]: alcohol consumption; [18]: illegal drug use during pregnancy; [19]: newborn sex; [20]: delivery mode; [21]: age at the time of heel stick; [22]: prenatal vitamin use; [23]: Log10-PCB 153; [24]: delivery by Cesarean section; [25]: gestational week at delivery; [26]: menopausal status; [27]: occupation; [28]: total cholesterol; [29]: triglycerides; [30]: HDL-cholesterol; [31]: LDL-cholesterol; [32]: thyroglobulin antibody; [33]: thyroid peroxidase antibodies; [34]: weight loss; [35]: maternal age; [36]: health insurance provider, [37]: urinary specific gravity; [38]: days of mass screening test; [39]; thyroid hormones; [40]: study site; [41]: disease status; [42]: BSA; [43]: iodized salt consumption; [44]: total cholesterol; [45]: TgAb; [46]: TPOAb; [47]: obesity and other related diseases; [48]: medication; [49]: medical history; [50]: other EDCs.