Urinary Concentration of Phthalate Metabolites in Women With and Without Endometriosis

NCT ID: NCT05551494

Last Updated: 2022-09-22

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 440 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-03-22
• Study Completion Date: 2024-03-30

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.

Conditions

Endometriosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Endometriosis group

Cases will include women aged 18-45 with a surgical diagnosis of endometriosis in the previous 24 months or with a current nonsurgical diagnosis of endometriosis who report having lived in the past ten years in the Lombardy area. At study entry, we will collect urinary sample.

Urinary sample

Intervention Type: DIAGNOSTIC_TEST

At study entry, we will collect urinary samples from women. Participants will be asked with an interview on demographic and lifestyle characteristics, health-related behaviours, the existence and duration of infertility, medical history, and history of hormonal or surgical treatments for endometriosis. Pain symptoms will be evaluated through a 10 cm long one-dimensional visual-analogue scale (VAS).

In addition, women will be asked to report about their habits about consumption of plastic

Control group

Control group are women aged 18-45 attending our outpatient clinic for periodical gynaecological care, contraception, or cervical cancer screening programme, and without a previous clinical or surgical diagnosis of endometriosis who report having lived in the past ten years in the Lombardy area. At study entry, we will collect urinary sample.

Urinary sample

Intervention Type: DIAGNOSTIC_TEST

At study entry, we will collect urinary samples from women. Participants will be asked with an interview on demographic and lifestyle characteristics, health-related behaviours, the existence and duration of infertility, medical history, and history of hormonal or surgical treatments for endometriosis. Pain symptoms will be evaluated through a 10 cm long one-dimensional visual-analogue scale (VAS).

In addition, women will be asked to report about their habits about consumption of plastic

Interventions

Urinary sample

At study entry, we will collect urinary samples from women. Participants will be asked with an interview on demographic and lifestyle characteristics, health-related behaviours, the existence and duration of infertility, medical history, and history of hormonal or surgical treatments for endometriosis. Pain symptoms will be evaluated through a 10 cm long one-dimensional visual-analogue scale (VAS).

In addition, women will be asked to report about their habits about consumption of plastic

Intervention Type: DIAGNOSTIC_TEST

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Direzione Ginecologia

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laura Buggio, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Locations

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Paolo Vercellini, Professor

Role: CONTACT

paolo.vercellini@unimi.it

0255032218

Laura Buggio, MD

Role: CONTACT

laura.buggio@policlinico.mi.it

0255032218

Facility Contacts

Laura buggio, MD

Role: primary

laura.buggio@policlinico.mi.it

+393388720855

Dhouha Dridi, MD

Role: backup

dhouha.dridi@policlinico.mi.it

+393429370961

Other Identifiers

2706

Identifier Type: -

Identifier Source: org_study_id