Unravelling the link between phthalate exposure and endometriosis in humans: a systematic review and meta-analysis of the literature

Conforti, Alessandro; Carbone, Luigi; Simeon, Vittorio; Chiodini, Paolo; Marrone, Vincenzo; Bagnulo, Francesca; Cariati, Federica; Strina, Ida; Alviggi, Carlo

doi:10.1007/s10815-021-02265-3

Cited by 13 publications

(4 citation statements)

References 75 publications

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“…Our findings are consistent with those of the previous studies [21], [22]. However, our findings are not in agreement with another previous study that has not discovered a significant connection between DEHP levels and endometriosis (p = 0.161), but a statistically significant weak association between MEHP levels and endometriosis (p = 0.020) in their case-control study [23].…”

Section: Discussionsupporting

confidence: 72%

Association of Phthalate Exposure with Endometriosis and Idiopathic Infertility in Egyptian Women

EL-Desouky

Elyamany²,

Hanon³

et al. 2022

Open Access Maced J Med Sci

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BACKGROUND: Phthalates are compounds found in medical supplies, cellophane wraps, beverage containers, metal can linings, and other products. They have the potential to be significant endocrine disruptors. In experimental animals, thereby affecting their reproductive capacity. Endometriosis is a gynecological condition defined by ectopic endometrial glands and stromal development. Exposure to phthalates has been linked to the development of endometriosis in numerous studies. The dangers of phthalates to women’s reproductive health and fertility have been widely reported. AIM: So far, the relationship between phthalates and infertility is not proven so we decided to see if there was a link between the urine phthalate metabolite levels and endometriosis or idiopathic infertility in Egyptian women. METHODS: Our research was carried out at the infertility outpatient clinic of the Faculty of Medicine of Cairo University. It included 100 female subjects aged 18−40-years-old. Group A (idiopathic infertility; n = 40), Group B (endometriosis; n = 40), and Group C (control; n = 20) were the three age-matched groups that were studied. Using high-performance liquid chromatography (HPLC), the urine levels of mono-2-ethylhexyl phthalate (MEHP) were quantified. RESULTS: The comparison between the study groups has revealed statistically significant differences regarding the urine MEHP levels between Groups A and B. An analysis of the urine MEHP levels in the study Groups A and B has also revealed that the significantly higher urinary MEHP levels are correlated with the use of dietary plastic containers, the use of cosmetics, and the patients’ estrogen levels. Moreover, the urinary MEHP levels of Group A were associated with a history of abortions. CONCLUSIONS: Higher levels of urinary MEHP are positively associated with female reproductive disorders, specifically endometriosis, idiopathic infertility, and abortion.

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Section: Discussionsupporting

confidence: 72%

Association of Phthalate Exposure with Endometriosis and Idiopathic Infertility in Egyptian Women

EL-Desouky

Elyamany²,

Hanon³

et al. 2022

Open Access Maced J Med Sci

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“…In the case of endometriosis, a significant increase in the risk of develop endometriosis has been estimated in women with higher DEHP exposure (OR = 1.42; 95% CI: 1.19–1.70) [ 10 ]. In addition, in other studies, higher levels of both the parental compound and its metabolites (MEHP, MEHHP, and MEOHP) have been detected in the plasma, serum, peritoneal fluid, and urine of women with endometriosis compared with healthy controls [ 5 , 11 , 12 , 13 , 14 , 15 , 16 ]. One of the mechanisms that could explain the relationship between DEHP exposure and an increased risk of endometriosis could be the induction of the above-mentioned molecular abnormalities in the eutopic endometrium of women with endometriosis.…”

Section: Introductionmentioning

confidence: 89%

“…Endocrine disrupting chemicals (EDCs) interfere with hormonal and immunological signaling and alter the epigenetics of target cells [ 3 , 4 ]. Specifically, a link between phthalate exposure and the risk of endometriosis has been described in several population-based case-control studies [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Endometrial Cells Acutely Exposed to Phthalates In Vitro Do Not Phenocopy Endometriosis

González-Martín

Palomar

Medina-Laver

et al. 2022

IJMS

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Environmental factors that have been linked to an increased endometriosis risk include exposure to di-(2-ethylhexyl)-phthalate (DEHP), an endocrine disruptor. This study aims to investigate whether DEHP in vitro exposure in primary endometrial stromal cells (EnSC), primary endometrial epithelial cells (EnEC), and the human endometrial adenocarcinoma cell line Ishikawa properly mimics alterations described in the eutopic endometrium of women with endometriosis. Primary EnSC and EnEC, isolated from six fertile egg donors, and Ishikawa cells were exposed to DEHP (0.1, 1, and 10 µM) and were assessed for viability, endometriosis markers (IL-6, VEGF-A, HOXA10, EZH2, and LSD1), steroid receptor gene expressions (ER-1, ER-2, PR-T, PR-B, and PGRMC1), and invasive capacity. Viability after 72 h of DEHP exposure was not significantly affected. None of the endometriosis markers studied were altered after acute DEHP exposure, nor was the expression of steroid receptors. The invasive capacity of EnSC was significantly increased after 10 µM of DEHP exposure. In conclusion, acute DEHP exposure in primary endometrial cells does not fully phenocopy the changes in the viability, expression of markers, or steroidal receptors described in endometriosis. However, the significant increase in EnSC invasiveness observed after DEHP exposure could be a link between DEHP exposure and increased endometriosis likelihood.

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“…Huan et al found that exposure to PAEs, especially DEHP, was associated with the occurrence of endometriosis ( Yi et al, 2023 ). In a meta-analysis, Conforti et al found that endometriosis was associated with increased urinary levels of MBP/MnBP, MEOHP, and MEHHP, but not for others ( Conforti et al, 2021 ).…”

Section: Reproductive Toxicity Of Phthalic Acid Estersmentioning

confidence: 99%

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women

Wang,

Zhao,

Feng

et al. 2024

Front. Cell Dev. Biol.

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Recently, there has been a noticeable increase in disorders of the female reproductive system, accompanied by a rise in adverse pregnancy outcomes. This trend is increasingly being linked to environmental pollution, particularly through the lens of Endocrine Disrupting Chemicals (EDCs). These external agents disrupt natural processes of hormones, including synthesis, metabolism, secretion, transport, binding, as well as elimination. These disruptions can significantly impair human reproductive functions. A wealth of animal studies and epidemiological research indicates that exposure to toxic environmental factors can interfere with the endocrine system’s normal functioning, resulting in negative reproductive outcomes. However, the mechanisms of these adverse effects are largely unknown. This work reviews the reproductive toxicity of five major environmental EDCs—Bisphenol A (BPA), Phthalates (PAEs), Triclocarban Triclosan and Disinfection Byproducts (DBPs)—to lay a foundational theoretical basis for further toxicological study of EDCs. Additionally, it aims to spark advancements in the prevention and treatment of female reproductive toxicity caused by these chemicals.

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Unravelling the link between phthalate exposure and endometriosis in humans: a systematic review and meta-analysis of the literature

Cited by 13 publications

References 75 publications

Association of Phthalate Exposure with Endometriosis and Idiopathic Infertility in Egyptian Women

Association of Phthalate Exposure with Endometriosis and Idiopathic Infertility in Egyptian Women

Endometrial Cells Acutely Exposed to Phthalates In Vitro Do Not Phenocopy Endometriosis

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women

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