Breast, Environmental Exposure, Puberty, Precocious
Conditions
Keywords
Early puberty, Endocrine disruptors, Girls, Breast growth, Environmental Health Measure
Brief summary
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
OTHEREnvironmental 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 pediatric odontology researchers on the on molar and incisor hypomineralization, known as MIH.
Sponsors
Lille Catholic University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
6 Years to 8 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of the weight | Baseline, 3 months, 6 months | This parameter will allow to describe the clinical evolution of the weight after application of environmental health measures |
| Change from baseline of the height | Baseline, 3 months, 6 months | This parameter will allow to describe the clinical evolution of the height after application of environmental health measures |
| Body mass index (BMI) | Baseline, 3 months, 6 months | This parameter will allow to describe the clinical evolution of the BMI after application of environmental health measures |
| Change from baseline of the size of the breast development measured by Magnetic Resonance Imaging | Baseline, 3 months | This parameter will allow to describe the clinical evolution of breast development after application of environmental health measures |
| Change from baseline of the size of ovaries/uterus measured by Magnetic Resonance Imaging | Baseline, 3 months, | This parameter will allow to describe the clinical evolution of ovaries and uterus after application of environmental health measures |
| Change from baseline of the abdominal fat surface measured by Magnetic Resonance Imaging | Baseline, 3 months | This parameter will allow to describe the clinical evolution of the abdominal fat surface after application of environmental health measures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone age determination by X ray | Change from baseline at 90 | Determination of bone age to determine the maturity of the child's skeletal system. |
| Degree of severity of teeth hypomineralisation | Baseline, 3 months | The dree of severity is determine according to a scale: 1: \<30% of the tooth's enamel surface area visibly disrupted, 2: 31 to 49% of the tooth's enamel surface area visibly disrupted, 3: \>50% of the tooth's enamel surface area visibly disrupted |
| Follicle-stimulating hormone (FSH) level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Estradiol (E2) level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Testosterone Level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| 17 hydroxyprogesterone level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Dehydroepiandrosterone sulfate level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Sex Hormone-Binding Globulin level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Thyroid Stimulating Hormone level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| FT4 (Free Thyroxine hormone) level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Androstenedione level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Insulin level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Insulin-like Growth Factor-1 level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Glycated hemoglobin (HbA1C) level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Leptine level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Luteinizing hormone (LH) level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Glycemia level | Change from baseline at 90 days and 180 days | Blood test for determining the evolution of this parameter from baseline |
| Measurement of endocrine disruptors in hair | Change from baseline at 90 days | Describe the evolution of the amount of endocrine disruptors in hair after the implementation of environmental health measures. from 70 to 100 mg of hair will cut as close as possible to the scalp at the posterior vertex, and stored at room temperature to measure endocrine disruptors such as parabens, phthalates, bisphenols and pesticides. |
| Tanner scale | Change from baseline at 90 and 180 days | The Tanner scale is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on external primary and secondary sex characteristics. Breast: Tanner I: no glandular tissue Tanner II: breast bud forms, areola begins to widen Tanner III: breast begins to become more elevated, and extends beyond the borders of the areola, Tanner IV: increased breast sizing and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast Tanner V: breast reaches final adult size Pubis hair: Tanner I: no pubic hair Tanner II: small amount of long, downy hair Tanner III: hair becomes more coarse and curly, and begins to extend laterally Tanner IV: adult-like hair quality, extending across pubis but sparing medial thighs Tanner V: hair extends to medial surface of the thighs |
Countries
France
Contacts
CONTACTMarie-Paule LEBITASY
CONTACTElodie MOUTAILLER
PRINCIPAL_INVESTIGATORPatricia RANNAUD-BARTAIRE, PhD
Hôpital Saint-Vincent de Paul
Outcome results
None listed