Early Breast Growth in Girls Aged 6 to 8 Years in the Current Environmental Context

Official title

Early Breast Growth in Girls Aged 6 to 8 Years in the Current Environmental Context: Clinical and Biological Parameters, Level of Impregnation With Endocrine Disruptors and Evaluation of the Impact of Environmental Health Measures

Overview

Various studies show an increase in the number of cases of early puberty in girls with breast development with a variable clinical presentation and evolution. This increasing phenomenon concerns girls between 6 and 8 years old. In a large number of cases, from 70 to 95% depending on the series, no medical cause is found and environmental factors are suspected to be involved. Descriptive studies of these patients are scarce and not always provide an overview of all the parameters in line with the concept of the exposome. The PENELOPE clinical trial will allow to analyze a large number of parameters, including the adipose tissue, its metabolism, the endocrine disruptors, and the epigenetic modifications, and to study the impact of environmental health measures in the evolution of these parameters. The data from the analyses of the endocrine disruptors of the patients will be explored in parallel in experimental models (amphibians, murine, cellular) in order to test potential mechanistic hypotheses.

Interventions

• Other Environmental health measures
  MRI will be used to confirm the presence of breast buds, to measure the size of the ovaries and uterus, as well as the fraction of fat mass (abdominal, subcutaneous, liver and bone marrow). The bood and urine tests will allow to measure different biological and metabolic parameters. The presence of endocrine disruptors will be determined in the hair. The bone age x ray will be estimate the maturity of the child's skeletal system. Photographs of the teeth will also be taken to be studied by pedia

Primary outcome measures

• Change from baseline of the size of the breast development measured by Magnetic Resonance Imaging [Time frame: Baseline, 3 months]
• Change from baseline of the size of ovaries/uterus measured by Magnetic Resonance Imaging [Time frame: Baseline, 3 months,]
• Change from baseline of the abdominal fat surface measured by Magnetic Resonance Imaging [Time frame: Baseline, 3 months]
• Change from baseline of the weight [Time frame: Baseline, 3 months, 6 months]
• Change from baseline of the height [Time frame: Baseline, 3 months, 6 months]
• Body mass index (BMI) [Time frame: Baseline, 3 months, 6 months]

Secondary outcome measures (12)

• Measurement of endocrine disruptors in hair [Time frame: Change from baseline at 90 days]
• Tanner scale [Time frame: Change from baseline at 90 and 180 days]
• Bone age determination by X ray [Time frame: Change from baseline at 90]
• Degree of severity of teeth hypomineralisation [Time frame: Baseline, 3 months]
• Follicle-stimulating hormone (FSH) level [Time frame: Change from baseline at 90 days and 180 days]
• Estradiol (E2) level [Time frame: Change from baseline at 90 days and 180 days]
• Testosterone Level [Time frame: Change from baseline at 90 days and 180 days]
• 17 hydroxyprogesterone level [Time frame: Change from baseline at 90 days and 180 days]
• Dehydroepiandrosterone sulfate level [Time frame: Change from baseline at 90 days and 180 days]
• Sex Hormone-Binding Globulin level [Time frame: Change from baseline at 90 days and 180 days]
• Thyroid Stimulating Hormone level [Time frame: Change from baseline at 90 days and 180 days]
• FT4 (Free Thyroxine hormone) level [Time frame: Change from baseline at 90 days and 180 days]

Eligibility criteria

For patients:

Inclusion criteria

• Girls aged 6 to 8 years
• Presenting a breast development (isolated or not)
• Undergoing scheduled pediatric day hospital care (HDJ)
• Who agree to participate in the study
• Whose parents agree to their child's participation in the study
• French speaking
• Whose parents speak French
• Affiliated to social security

Exclusion criteria

• Organic brain causes of precocious puberty: History of neurocerebral disease (malformations, developmental abnormalities)
• Organic causes of precocious puberty: Mac Cune Albright syndrome, ovarian cyst or tumor and adrenal hyperplasia
• History of chemotherapy or radiation therapy
• Presenting with a communication disorder
• Pregnancy
• Persons under protective measures
• Persons deprived of liberty for judicial or administrative reasons

For controls:

Inclusion criteria

• Girls aged 6 to 8
• Tanner stage 1: Absence of breasts and hairiness
• Coming for routine consultation in the pediatric HDJ at Saint-Vincent-de-Paul hospital, or at the BLM practice in Lambersart, or to radiology for an MRI for another medical other medical reason
• Agree to participate in the study
• Whose parents agree to their child's participation in the the study
• French-speaking
• Whose parents speak French
• Affiliated with social security

Exclusion criteria

• Signs of puberty (Tanner stages 2, 3, 4 and 5 for breast development) breast development)
• Previous chemotherapy or radiotherapy
• Presenting a communication disorder
• Pregnant women
• Persons under protective supervision
• Persons deprived of their liberty for judicial or administrative reasons

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

France · 2 centers

• Cabinet BLM — Lambersart
• Saint Vincent hospital — Lille

Identifiers

NCT: NCT06083415 · RT-17

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗