Table 1.
Description of the investigations conducted with respect to phthalates and/or bisphenols exposure and endometriosis.
| Ref. | Substance | Type of Study | Sample | Biomarkers and Concentrations | Results | Considerations |
|---|---|---|---|---|---|---|
| [24] | BPA a | cross-sectional | 166 women with endometriosis | Urinary BPA (μg/g creat. b) 0.80 (median) |
No correlation was found between urinary BPA levels and disease severity. | Mean BPA values did not differ significantly between women with stage 0–I (0.74μg/g creat.) of endometriosis severity compared to stage II–IV (0.93 μg/g creat.). |
| [25] | BPA and BPB c | case-control | 58 women with endometriosis, 11 women controls | Serum BPA and BPB (μg/L) BPA 2.91 vs. 0.00 BPB 5.15 vs. 0.00 (arithmetic mean) |
None of the control biological samples showed the presence of BPA or BPB, whereas there was presence in 63.8% of cases. | The sample size and the absence of an evaluation of statistical significance make the data indicative but not usable for the purpose of an evaluation of correlation with onset of the disease. |
| [26] | BPA and phthalates | case-control | 30 women cases, with laparoscopic diagnosis of endometriosis and 22 women controls | Urinary BPA and phthalate metabolites. (μg/g creat.) BPA: 9.78 vs. 8.80 MMP d 62.8 vs. 105.0 MiBP e 185.0 vs. 183.0 MnBP f 83.3 vs. 76.3 MCHP g 12.6 vs. 6.87 MEHP h 30.4 vs. 30.2 MiNP i 73.2 vs. 18.9 MOP j 670.0 vs. <LOQ MBzP k 23.8 vs. <LOQ (arithmetic mean) |
Absence of statistically significant differences between the two groups. For monoisobutyl phthalate, an OR l = 1.93, 95% CI m 0.51–7.33) was obtained but not significant (χ2). | The sample size can greatly affect the consistency of the study outcome. |
| [23] | BPA, BPF n and BPS o | case-control | 35 women with laparoscopic diagnosis of endometriosis, and 89 women controls | Urinary BPA, BPF, BPS (μg/g creat.) BPA 3.6 vs. 3.0 BPS 0.1 vs. 0,2 BPF 0.1 vs. 0.1 (geometric mean) |
There is an increased risk between: BPA exposure and endometriosis- OR 1.5, 95% CI 1.0–2.3; exposure to the sum of three alkylphenols (BPA, BPF, BPS) and endometriosis -OR = 1.5, 95% CI 0.9–2.3. | Exposure to BPA is suggestive of a greater risk of endometriosis, but the study sample is numerically limited. |
| [27] | phthalates | case-control | 55 women with endometriosis, 33 women controls | Urinary phthalate metabolites (μg/g creat.) MEHHP p 18.2 vs. 12.9 MEOHP q 13.4 vs. 10.3 MnBP 41.7 vs. 32.4 MBzP 5.8 vs. 7.3 MECPP r 23.8 vs. 19.0 (arithmetic mean) |
The association between MEHHP and MEOHP levels (both metabolites of DEHP s) and endometriosis was significant. | The data were suggestive of a possible association between exposure and endometriosis, but the sample size can considerably affect the robustness of the study, in addition to the reduced number of controls compared to cases. |
| [28] | phthalates | case-control | 85 women with laparoscopic diagnosis of endometriosis and 135 women controls | Blood phthalates. (μg/mL) DnBP t 0.44 vs. 0.15 BBzP u 0.66 vs. 0.11 DnOP v 3.32 vs. 0.00 DEHP 2.44 vs. 0.45 (arithmetic mean) |
Statistically significant differences emerged between the controls and the group of women with stage I and IV of endometriosis severity; in particular for DnBP, BBzP, DEHP and DnOP (p <0.05 ANOVA w). | The results were indicative of a correlation between exposure to some phthalates and the onset of endometriosis. |
| [29] | phthalates | case-control | 92 women with endometriosis and 195 women controls | Urinary phthalate metabolites (μg/g creat.) MEHP 2.2 vs. 3.4 MEHHP 14.8 vs. 18.8 MEOHP 8.1 vs. 10.8 MBzP 4.5 vs. 5.0 MEP x 61.9 vs. 43.9 MECPP 14.4 vs. 18.0 MiBP 1.3 vs. 1.5 MnBP 9.8 vs. 10.0 (median) |
Inverse association between urinary levels of the DEHP metabolites and endometriosis was found, while a direct correlation for MBzP and MEP was identified, both without statistical significance. | Controversial data in terms of risk for incidence of endometriosis emerged, different by type of phthalate. |
| [30] | phthalates | case-control | 97 women with endometriosis and 169 women controls | Blood phthalates (μg/L) MEHP 17.4 vs. 12.4 DEHP 179.7 vs. 92.5 (arithmetic mean) |
There was a statistically significant difference between cases and controls in DEHP blood levels (179.7 ± 32.5 ng/mL vs. 92.5 ± 31.1 ng/mL) with a weak but significant association with MEHP (OR = 1.020, 95% CI 1.003–1.038 p = 0.020). | In the stratification of the sample with respect to the stages of severity of endometriosis, the data suggest a correlation between exposure and disease. The blood determination of phthalates carries a greater risk of contamination by laboratory plastic material than the urinary determination of metabolites. |
| [31] | phthalates | cross-sectional | 1227 women with self-reported diseases—of which 87 with endometriosis | Urinary phthalate metabolites (μg/L) MEHP 2.5 vs. 3.4 MBP 28.9 vs. 25.5 MEP 207.0 vs. 219.9 MBzP 14.4 vs. 14.1 MEHHP 16.5 vs. 19.7 MEOHP 11.5 vs. 13.5 (geometric mean) |
An association between endometriosis and exposure to MnBP, OR 1.36 (95% CI 0.77–2.41) and an inverse association with MEHP OR = 0.44 (95% CI 0.19–1.02) were identified. | Need for confirmation of data in prospective and case-control studies. |
| [32] | phthalates | case-control | 57 women with laparoscopic diagnosis of endometriosis and 80 women controls (stage 0–I endometriosis severity) | Urinary phthalates metabolites (μg/L) MnBP 26.5 vs. 20.0 MMP 12.0 vs. 8.3 MEHP 8.9 vs. 5.4 MEHHP 17.6 vs. 9.1 MEOHP 8.0 vs. 3.7 (arithmetic mean) |
The comparison between the urinary levels of MEHP, MnBP, MBzP, MEHHP did not reveal a significant correlation between exposure to phthalates and endometriosis. | The results do not support the hypothesis of a greater risk of endometriosis in the case of greater exposure to phthalates. |
| [33] | phthalates | case-control | 49 infertile women with endometriosis; 38 infertile women controls but without endometriosis; 21 fertile women without endometriosis | Blood phthalates (μg/L) Stage IV ofendometriosis severity vs. controls: DnBP 1.05 vs. 0.11 BBzP 1.27 vs. 0.14 DEHP 4.39 vs. 0.48 DnOP 5.35 vs. 0.03 (arithmetic mean) |
The cases showed significantly higher values of DnBP, BBzP, DnOP and serum DEHP compared to the two control groups. Furthermore, the correlation between phthalates and the severity of endometriosis seemed statistically significant. | The study supports the hypothesis of correlation between exposure to phthalates and the onset of endometriosis, although the sample size is particularly low. The blood determination of phthalates carries a greater risk of contamination by laboratory plastic material than the urinary determination of metabolites. |
| [34] | phthalates | case-control | 28 women with laparoscopic diagnosis of endometriosis, 29 women controls | Urinary phthalate metabolites (μg/g creat.) MnBP 94.1 vs. 58.0 MMP 52.4 vs. 32.1 MEP 58.0 vs. 71.4 MBzP 12.2 vs. 8.9 MEHP 4.2 vs. 3.4 5-oxo-MEHP y 19.0 vs. 7.8 5-OH-MEHP z 16.7 vs. 9.9 (arithmetic mean) |
The cases showed higher urinary levels of MnBP (94.1 vs. 58.0 μg/g creat.) than controls. | The same authors suggested producing further studies of greater statistical strength to confirm the data relating to the possible association between exposure to phthalates and endometriosis. |
| [35] | BPA | case-control | 143 women with laparoscopic diagnosis of endometriosis. 287 women controls | Urinary BPA (μg/g creat.) 1.32 vs. 1.24 (median) |
Total BPA urinary levels did not show differences between cases and controls and no correlation with the different stages of severity of the disease was found. | Limitations of the study: the sampling time of the biological material (single urine spot sample); the absence of disease in the controls was self-declared, which could make the control sample not entirely suitable. |
| [36] | BPA | case-control | 68 women with endometriosis and 60 women controls | Urinary BPA (μg/L) 5.31 vs. 1.64 (arithmetic mean) |
A significant difference between cases and controls in BPA urinary levels was found. Conflicting data emerged with respect to the identification of work activities potentially at greater risk of endometriosis and/or exposure to BPA. | The data relating to work activity were collected with self-administration of a questionnaire. This generated mixed data. The authors underlined the need to structure exposure studies directly in specific work environments. |
| [11] | phthalates | case-control (matched cohort design) |
495 women of “operative cohort” (190 with endometriosis) and 131 women of the “population cohort” (14 with endometriosis) | Urinary BPA and phthalate metabolites (μg/L) (operative/population cohort) BPA 1.5 vs. 1.6/4.2 vs. 1.7 MMP 2.1 vs. 2.4/3.7 vs. 2.7 MEP 107.2 vs. 109.6/ 152.0 vs. 138.2 MCPP A 2.7 vs. 3.4/ 5.8 vs. 4.1 MnBP 12.1 vs. 11.0/ 19.1 vs. 11.2 MECCP 24.7 vs. 22.0/54.2 vs. 20.3 MCMHP B 29.3 vs. 29.2/ 53.5 vs. 22.5 MEHHP 16.3 vs. 14.4/ 32.4 vs. 11.9 MEOHP 11.0 vs. 10.1/ 23.0 vs. 8.3 MCHP 0.03 vs. 0.04/ 0.04 vs. 0.03 MBzP 7.0 vs. 7.8/ 9.9 vs. 6.5 MEHP 4.8vs. 4.1/ 8.3 vs. 3.1 MOP 0.06vs0.06/ 0.06 vs. 0.05 MiNP 0.16vs0.16/ 0.22 vs. 0.16 (geometric mean) |
Urinary levels of the metabolites of 6 phthalates were associated with an increase in the diagnosis of endometriosis and in particular for MnOP (OR 1.38, 95% CI 1.10–1.72) and MEHP (OR 1.35, 95% CI 1.03–1.78). | The greatest significance was observed in sub-populations including laparoscopic and cytological diagnoses. |
a BPA—bisphenol A; b creat. —creatinine; c BPB—bisphenol B; d MMP—monomethylphthalate; e MiBP—mono isobutylphthalate; f MnBP—mono-n-butylphthalate; g MCHP—monocyclohexylphthalate; h MEHP—mono(2-ethylhexyl)phthalate; i MiNP—mono iso-nonylphthalate; j MOP—mono n-octylphthalate; k MBzP—monobenzylphthalate; l OR—Odds ratio; m CI—confidence interval; n BPF—bisphenol F; o BPS—bisphenol S; p MEHHP—mono(2-ethyl-5-hydroxyhexyl)phthalate; q MEOHP—mono(2-ethyl-5-oxohaxyl)phthalate; r MECPP—mono(2-ethyl-5-carboxypentyl) phthalate; s DEHP—di(2-ethylhexyl)phthalate; t DnBP—di-n-butylphthalate; u BBzP—butylbenzylphthalate; v DnOP—di-n-octylphthalate; w ANOVA—analysis of variance; x MEP—monoethylphthalate; y 5-oxo-MEHP—mono(2-ethyl-5-oxo-hexyl)phthalate; z 5-OH-MEHP—Mono-(2-ethyl-5-hydroxyhexyl) phthalate; A MCPP—Mono (3-carboxypropyl) phthalate; B MCMHP—mono(2-carboxymethylhexyl) phthalate.