Clinical trial NCT05551494: Urinary Concentration of Phthalate Metabolites in Women With and Without Endometriosis
Official title: Urinary Concentration of Phthalate Metabolites in Women With and Without Endometriosis: a Case-control Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Endometriosis
Keywords: phthalates
urinary biomarkers
endometriosis
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2022-09-22
Enrollment: 440
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: In this study will be recruited women with or without endometriosis, aged 18-45 years who have lived in the last 10 years in the Lombardy area. Will be excluded women with uterine fibroids, gynecological cancers or renal, hepatic, cardiovascular disease, diabetes or high blood pressure

Brief summary: Exposure to endocrine-disrupting chemicals can considerably affect female reproductive system. Exposure can occur in living environments and in specific workplaces in which these substances are produced or used. Among endocrinedisrupting chemicals, phthalates, dialkyl esters or alkyl aryl esters of orthophthalic acid (1,2-dicarboxylic acid) represent a group of structurally similar molecules, widely used in industry since 1930 in numerous manufacture processes, mainly as a plasticizer.

These substances present dangerous characteristics, particularly associated with reproductive toxicity, and their xenoestrogenicity led some authors to evaluate a possible involvement in the aetiology of endometriosis.

In this proposed study the investigators aim to clarify a potential association between endometriosis and phthalates exposure.

Women with a diagnosis of endometriosis will be recruited as "cases" while women without endometriosis as "controls". An "ad hoc" questionnaire will be administered to the patient to collect the necessary information on the characteristics of endometriosis as well as their lifestyle and work habits.

The biological monitoring will be carried out measuring the urinary levels of phthalate metabolites. In order to produce reliable data and to reduce the possible contamination caused by the contact with plastic materials, samples will be analyzed by High Performance Liquid Chromatography/Tandem Mass Spectrometry (HPLC-MS/MS).

A statistical elaboration of the data will clarify possible identifiable risk factors and associations with specific clinical situations.

The investigators expect that women with endometriosis may present higher levels of phthalates compared with women without the disease. In particular, the investigators hypothesize that women with the most severe form of the disease \[i.e. deep infiltrating endometriosis (DIE)\] may present the highest levels. These study findings will provide valuable suggestions for developing effective strategies to prevent endometriosis.

Detailed description: Exposure to phthalates can considerably affect female reproductive system. Recent evidence suggests that one of the diseases related to the high concentration of phthalate metabolites in biological fluids might be endometriosis.

This case-control study aims to evaluate the relationship between endometriosis and phthalates exposure through biomarkers analysis in urine. The investigators hypothesize that women with endometriosis, particularly those with deep infiltrating forms (i.e. the most severe form of the disease), will show higher urinary phthalate metabolites compared to women with ovarian/peritoneal forms and those without endometriosis. When deep lesions and ovarian lesions co-existed, the woman will be included in the deep infiltrating subgroup, as the former lesions are considered more severe than the latter ones.

The identification of a possible environmental risk, such as the exposure to phthalates, could allow the implementation of preventive measures aimed at reducing the exposure to such contaminants. Moreover, clinical data obtained may contribute to a better understanding of the etiology and the pathophysiology of endometriosis.

The main objective of the present study is to evaluate the levels of exposure to phthalates of a female population with endometriosis and to understand if it differs significantly from a population of women without the disease.

Identifying a possible relationship between urinary phthalates metabolite concentrations and the risk of endometriosis could represent a valuable tool for implementing specific preventive measures, especially in the workplace.

The results of our case-control study aim to shed more light on the potential association between endometriosis and phthalate exposure, specifically in the Italian context.

Secondary objectives include:

1. to evaluate potential variations in urinary phthalate metabolite levels in women with different phenotypes of the disease: peritoneal endometriosis, ovarian endometriosis, deep infiltrating endometriosis.
2. to evaluate potential variations in the levels of urinary phthalate metabolite in endometriosis patients in relation to the presence and levels of pain symptoms (dysmenorrhea, chronic pelvic pain, deep dyspareunia) and/or infertility.

The causality study will try to identify possible routes of exposure in everyday life and/or working environments, which could represent a possible source of risk. The results could identify work context in which health risks for women could be highly diversified from those for men. This identification could support the competent doctors in defining health surveillance protocols for specific sectors.

Eligibility criteria: Inclusion Criteria:

* Endometriosis group are women aged 18-45 with a diagnosis of endometriosis who report having lived in the past ten years in the Lombardy area.
* Control group are women aged 18-45 who do not have endometriosis who report having lived in the past ten years in the Lombardy area.

Exclusion Criteria:

* Pregnancy
* Uterine fibroids, gynecological cancers
* Renal, hepatic, cardiovascolar disease, diabetes or high blood pressure

Primary outcomes:
measure: Evaluate urinary concentration of phthalates
timeFrame: 24 months
Secondary outcomes:
measure: Variations in urinary concentration phthalate metabolite levels in women with different phenotypes of the disease
timeFrame: 24 months
measure: Variations in urinary concentration phthalate metabolite levels in women with different symptoms of the disease
timeFrame: 24 months
measure: Identify possible routes of exposure in everyday life and/or working environments
timeFrame: 24 months
measure: Identify work context in which health risks for women could be highly than for men
timeFrame: 24 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Laura Buggio, MD
role: PRINCIPAL_INVESTIGATOR
References: