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The Developmental Origins of Endometriosis

Recruiting
Conditions
Endometriosis
Interventions
Other: Blood samples for testosterone and SHBG measurements
Other: Saliva samples for oxytocin measurements
Registration Number
NCT05951452
Lead Sponsor
University Hospital, Montpellier
Brief Summary

Introduction:

Endometriosis is a common pathology affecting one in 10 women, characterized by the ectopic development of endometrium, which can cause pain and/or infertility. This pathology is primarily determined by hereditary factors, but it is also susceptible to environmental influences, such as the age of the onset of menstruation or exposure to chemical substances that modify the endocrine system. Recent studies have highlighted that endometriosis is more common in women with relatively short ano-genital distances (AGD), and that sensitivity to pain is closely linked to adult levels of testosterone (T) or oxytocin (OT).

Aim:

The main objective is to compare the anogenital distance (AGD) between two groups of women: one with stage III or IV endometriosis (ENDO +) and another group without endometriosis confirmed by laparoscopy (ENDO -).

The secondary objectives are to compare various factors between the 2 groups :

* Basal testosterone levels in blood.

* Variations in blood testosterone levels before and after a video stimulating empathy.

* Basal oxytocin levels in saliva.

* Variations in oxytocin levels in saliva before and after an empathy-stimulating video.

* Pelvic pain, between D2 and D5 after the start of the menstrual cycle.

For the ENDO + group only:

* Evaluate patients' quality of life, between D2 and D5 after the start of the menstrual cycle.

* Correlate pain experienced over the last 4 weeks with hormonal markers (AGD, T, OT).

Methods:

Participants in the ENDO+ group will fill in a questionnaire assessing the impact of pain experienced over the past 4 weeks on their quality of life. D0 is defined as the day when participants experience a menstrual bleed before 10 am. All participants will return for project-specific hospital appointment between D2 and D5 after the start of their menstrual cycle to measure T, Sex Hormone-Binding Globulin (SHBG) and OT.

During this consultation, the following samples will be taken:

* 10mL blood sample

* 2mL saliva sample

Both samples will be taken at t0 (before watching the video) and t1 (20 minutes after watching the video).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
40
Inclusion Criteria
  • Nulliparous woman
  • No hormonal contraception for at least 3 months
  • Regular menstrual cycles (between 26 and 32 days) or proven ovulation (positive urine ovulation test ovulation test or progesterone level >3 ng/ml in the luteal phase)
  • Normal BMI (≥ 18,5 and < 30 kg/m²)

Specific criteria (ENDO+ group) :

  • Stage III or IV endometriosis confirmed by laparoscopy or by laparotomy or MRI
  • Painful symptoms

Specific criteria (ENDO- group) :

• Patient without endometriosis confirmed by laparoscopy

Exclusion Criteria
  • Ovarian stimulation planned within 3 months
  • Adenomyosis
  • Use of a copper coil
  • Polycystic ovary syndrome
  • Pudendal neuralgia
  • Episiotomy or lesion of the posterior perineum that may modify AGD
  • Diabetes or thyroid disease
  • Chronic liver failure, chronic renal failure, cardiac pathology, autoimmune disease
  • Autism
  • Diagnosis and/or treatment for psychiatric illness
  • Chronic exposure to cocaine, methamphetamine, morphine or ecstasy within 30 days before the inclusion visit
  • Chronic exposure to Tetrahydrocannabinol (THC) within 7 days prior to inclusion.
  • Patient on treatment(s) that vary oxytocin (e.g. atosiban), testosterone or GnRH
  • Pregnant or breast-feeding patient
  • Patients who have given birth or breastfed within 6 weeks before the inclusion visit
  • Patient unable to read French
  • Failure to obtain informed consent
  • Patient not affiliated with or not benefiting from a national health insurance scheme
  • Person under legal protection, guardianship or curatorship
  • Patient participating in other research involving the human person

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ENDO +Blood samples for testosterone and SHBG measurementsPatients with endometriosis diagnosed by Magnetic Resonance Imaging (MRI) or laparoscopy
ENDO +Saliva samples for oxytocin measurementsPatients with endometriosis diagnosed by Magnetic Resonance Imaging (MRI) or laparoscopy
ENDO -Saliva samples for oxytocin measurementsPatients without endometriosis diagnosed by laparoscopy
ENDO -Blood samples for testosterone and SHBG measurementsPatients without endometriosis diagnosed by laparoscopy
Primary Outcome Measures
NameTimeMethod
Measure of the anogenital distance (AGD)At diagnosis or at inclusion

AGD is measured at enrollment for patients already diagnosed by Magnetic resonance imaging (MRI), and it is measured during the laparoscopy once the diagnosis has been confirmed.

AGD is measured by 2 different operators with a millimetric precision ruler according 2 validated methods :

* measure of the distance from the clitoral surface to the anus (AGD-AC), and

* measure of the distance from the posterior fourchette to the anus (AGD-AF). The method is described here: https://www.jove.com/v/57912/ Each operator will measure the AGD-AC and the AGD-AF 3 times. For each type of AGD, the final value will correspond to the mean of the 6 values.

Secondary Outcome Measures
NameTimeMethod
Basal total testosteronet0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video

The basal total testosterone (Ttotal(t0)) level is measured in blood

Basal bio-available testosteronet0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video

The basal bio-available testosterone (Tbio-available(t0)) level is measured in blood

Basal sex hormone-binding globulint0 : Between the second and the fifth day of the menstrual cycle, before watching an empathy-inducing video

Basal sex hormone-binding globulin (SHBG(t0)) level is mesured in blood

Oxytocin (OT) level after empathy inductiont1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

The basal OT level is measured by the dosage in the saliva of :

Total OT (OTtotal(t1))

Bio-available testosterone after empathy inductiont1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

The bio-available testosterone level after empathy induction (Tbio-available(t1)) is measured in blood

Variation in bio-available testosterone levels before and after an empathy-inducing videot1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

The level of variation in bio-available testosterone before (t0) and after watching empathy-inducing video (t1) is assessed according to: Tbio-available(t1)-Tbio-available(t0)

% of variation in Free Androgen Index before and after an empathy-inducing videot1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

% of variation in Free Androgen Index before (t0) and after watching empathy-inducing video (t1) is assessed according to: \[\[FAI(t1)-FAI(t0)\]/FAI(t0)\] × 100

Variation in oxytocin (OT) level before and after an empathy-inducing videot1 : Between the second and the fifth day of the menstrual cycle, after wathching empathy-inducing video

Variation in OT level before (t0) and after watching an empathy-inducing video (t1) is assessed in the saliva according to:

- OTtotal(t1)-OTtotal(t0)

-% of variation of OT = \[\[OT(t1)-OT(t0)\]/OT(t0)\] × 100

Total testosterone after empathy inductiont1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

The total testosterone level after empathy induction (Ttotal(t1)) is measured in blood

Sex hormone-binding globulin after empathy inductiont1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

Sex hormone-binding globulin after empathy induction (SHBG(t1)) is mesured in blood

Area under the Receiving Operator Characteristic (ROC) curve for AGDAt diagnosis (ENDO+) or at enrollment (ENDO-)

The ROC curve is a graphical representation that illustrates the performance of a binary classification model. It plots the true positive rate (sensitivity) against the false positive rate (1 - specificity) at various classification thresholds. In other words, the model's sensitivity corresponds to the model's ability to detect patients (ENDO+) while the model's specificity corresponds to the model's ability to detect a non-patient (ENDO-). The ROC curve helps assess the model's ability to correctly identify true positives while minimizing false positives.

The area under the ROC curve (AUC) can be interpreted as the probability that, among two randomly chosen subjects, a patient and a non-patient, the value of the marker is higher for the patient than for the non-sick. An AUC of 0.5 (50%) indicates that the marker is non-informative. An increase in AUC indicates an improvement in discriminatory abilities, with a maximum of 1.0 (100%).

Pelvic pain intensityt0 : Between the second and the fifth day of the menstrual cycle, before watching an empathy-inducing video

Pelvic pain will be assessed using a Visual Analogue Scale (VAS). The visual analog scale (VAS) is a validated, unidimensional subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain."

Free Androgen Index after empathy inductiont1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

Free Androgen Index after empathy induction (FAI(t1)) = (Ttotal(t1)/SHBG(t1))\*100

Variation in Sex hormone-binding globulin levels before and after an empathy-inducing videot1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

The level of variation in Sex hormone-binding globulin before (t0) and after watching empathy-inducing video (t1) is assessed according to: SHBG(t1)-SHBG(t0)

Basal oxytocin (OT) levelt0 : Between the second and the fifth day of the menstrual cycle, before wathching an empathy-inducing video

The basal OT level is measured by the dosage in the saliva of :

Total OT (OTtotal(t0))

Basal Free Androgen Indext0 : Between the second and the fifth day of the menstrual cycle, before watching an empathy-inducing video

Basal Free Androgen Index (FAI(t0)) = (Ttotal(t0)/SHBG(t0))\*100

Variation in total testosterone levels before and after an empathy-inducing videot1 : Between the second and the fifth day of the menstrual cycle, after wathching an empathy-inducing video

The level of variation in total testosterone before (t0) and after watching empathy-inducing video (t1) is assessed according to: Ttotal(t1)-Ttotal(t0)

Trial Locations

Locations (1)

CHU de Montpellier

🇫🇷

Montpellier, France

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