Long-term Outcome of GnRH Analogues Treatment of Children With Idiopathic Central Precocious Puberty
- Conditions
- AdiposityPuberty, Precocious
- Interventions
- Other: GnRHas
- Registration Number
- NCT02790112
- Lead Sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Brief Summary
This study evaluates the influence of early adiposity rebound, genetic polymorphisms and GnRHa treatment on long-term outcome of girls with idiopathic central precocious puberty.
- Detailed Description
Gonadotropin-releasing hormone (GnRH) analogs are the mainstay of treatment for central precocious puberty (CPP) since 1985. The relatively short time period elapsed since the introduction of this therapy has not allowed until now to carry out exhaustive studies on the long-term evolution of treated patients. This project will analyze the long-term outcomes of patients with CPP treated or not with GnRHas on adult height, body mass index, body composition, metabolic disorders, bone mineralization, gonadal function, and fertility in comparison to a control group. Overweight before puberty is associated to earlier menarche, and conversely, earlier menarche predispose to adult obesity and metabolic disorders. Nevertheless, it is unclear if adult adiposity is a direct consequence of early puberty or if early puberty is a marker of a predisposition to excess adiposity from prepuberty through adult life. Recent data in rodent models support the hypothesis that early nutritional status determines a risk for both childhood and adult obesity and influences pubertal timing. In girls, early weight gain in childhood has been associated with early menarche. Pattern of growth rather than absolute level of fatness seem to be of most importance. So the first aim of this study is to compare the outcomes of CCP patients with or without an early adiposity rebound and to demonstrate that adiposity rebound more than CPP per se or the GnRHas therapy affect the outcomes. Moreover, recent genome-wide association studies have identified obesity-related gene variants associated with earlier age at menarche. The investigators hypothesized that there might be a genetic basis underlying the early programming of both childhood and adulthood adiposity and puberty timing. The investigators thus aim to determine if those obesity-related gene variants associated with an early but not precocious menarche could also be found in CPP, especially in girls with an early adiposity rebound and if their presence may affect adult health.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 418
- History of idiopathic CPP (ICPP) treated with GnRHas.
- A diagnosis of CPP made according to the following criteria: 1) secondary pubertal signs (Tanner stage 2) before 8 years in girls and 9 years in boys; 2) accelerated growth velocity (GV); 3) BA advanced for CA ≥ 1 year; 4) GnRH-stimulated peak LH >5 IU/L.
- A diagnosis of idiopathic CPP according the following criteria: 1) no hypothalamic-pituitary organic lesions at magnetic resonance imaging; 2) no known medical condition that might affect the onset of puberty.
- To determine whether the supposed long-term effects of treatment are instead consequences of the disease itself, untreated ICPP girls aged of ≥ 18 years, will also be included. For comparative purposes, age-matched normal (menarche > 10 y) volunteers will be recruited as a control group.
- In the treated ICCP group if 1) treatment with GnRHas for < 2 years; 2) non-compliance; 3) no gonadotropin suppression observed.
- For all patients: 4) small for gestational age; 5) chronic disease and/or treatment; 6) being < 4 years from menarche.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description GnRHas - controls patients GnRHas Compared long term outcome of treated patients with idiopathic central precocious puberty and control patients for: hormonal assessment; DNA for candidate single nucleotide polymorphisms (SNP) analyses; pelvic ultrasound; dual energy x-ray absorptiometry (DXA) Not GnRHas - Controls patients GnRHas Compared long term outcome of untreated patients with idiopathic central precocious puberty and control patients for: hormonal assessment; DNA for candidate single nucleotide polymorphisms (SNP) analyses; pelvic ultrasound; dual energy x-ray absorptiometry (DXA) GnRHas - Not GnRHas patients GnRHas Compared long term outcome of treated and untreated patients with idiopathic central precocious puberty : hormonal assessment; DNA for candidate single nucleotide polymorphisms (SNP) analyses; pelvic ultrasound; dual energy x-ray absorptiometry (DXA)
- Primary Outcome Measures
Name Time Method Single nucleotide polymorphisms (SNP) analyses 1 day DNA analyses
- Secondary Outcome Measures
Name Time Method Lumbar bone mineralization in Tscore 1 day Dual energy x-ray absorptiometry (DXA):
Body composition in % 1 day Dual energy x-ray absorptiometry (DXA): fat (visceral) and lean mass.
LDL-Cholesterol in mg/dl 1 day Metabolic assessment (fasting blood sampling)
Adult height in meters 1 day Measured at consultation
Total Cholesterol in mg/dl 1 day Fasting blood sampling
Abdominal perimeter in cm 1 day Measured at consultation
LH in IU/L 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Prolactine in microgr/L 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Endometrius thickness in mm 1 day Pelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Body mass index in kg/m2 1 day Calculated at consultation
Glucose in mg/dl 1 day Fasting blood sampling
Insulin in microU/ml 1 day Fasting blood sampling
Femoral neck bone mineralization in Tscore 1 day Dual energy x-ray absorptiometry (DXA):
SHBG by nmol/l 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Hip perimeter in cm 1 day Measured at consultation
Blood pressure in mmHg 1 day Measured at consultation
17 hydroxyprogesterone in ng/ml 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Ovaries volume in ml 1 day Pelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Ovaries follicles counting 1 day Pelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Oestradiol in ng/dl 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
DHEAS in micromol/l 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Inhibine in pg/ml 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Uterine diameter in mm 1 day Pelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Uterine volume in ml 1 day Pelvic ultrasound (at 2nd-5th day of the menstrual cycle)
HDL-Cholesterol in mg/dl 1 day Fasting blood sampling
Total bone mineralization in Tscore 1 day Dual energy x-ray absorptiometry (DXA):
Chronic anovulation in number 1 day Number of mentruals cycles in a year
Testicular volume in ml 1 day Measured at consultation
FSH in IU/L 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Anti-Müllerian Hormone in ng/ml 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Ovaries follicles diameter in mm 1 day Pelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Total serum testosterone by ng/dl 1 day Metabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Trial Locations
- Locations (1)
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium