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Long-term Outcome of GnRH Analogues Treatment of Children With Idiopathic Central Precocious Puberty

Influence of Early Adiposity Rebound, Genetic Polymorphisms and GnRHa Treatment on Long-term Outcome of Girls With Idiopathic Central Precocious Puberty.

Status
UNKNOWN
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02790112
Enrollment
418
Registered
2016-06-03
Start date
2016-04-30
Completion date
2018-10-31
Last updated
2016-06-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adiposity, Puberty, Precocious

Keywords

Body Mass Index, Body Composition, Glucose Metabolism Disorders, Bone Development, Gonadal Disorders, Fertility, Overweight, Obesity, Menarche

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.

Interventions

OTHERGnRHas

Influence of early adiposity rebound, genetic polymorphisms and GnRHa treatment on long-term outcome of treated and untreated girls with idiopathic central precocious compared to a control group. puberty.

Sponsors

Belgian Study Group for Pediatric Endocrinology
CollaboratorOTHER
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes

Inclusion criteria

* 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.

Exclusion criteria

* 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.

Design outcomes

Primary

MeasureTime frameDescription
Single nucleotide polymorphisms (SNP) analyses1 dayDNA analyses

Secondary

MeasureTime frameDescription
Ovaries follicles counting1 dayPelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Abdominal perimeter in cm1 dayMeasured at consultation
Hip perimeter in cm1 dayMeasured at consultation
Blood pressure in mmHg1 dayMeasured at consultation
Testicular volume in ml1 dayMeasured at consultation
LH in IU/L1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
SHBG by nmol/l1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Total serum testosterone by ng/dl1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Adult height in meters1 dayMeasured at consultation
Body mass index in kg/m21 dayCalculated at consultation
Body composition in %1 dayDual energy x-ray absorptiometry (DXA): fat (visceral) and lean mass.
Glucose in mg/dl1 dayFasting blood sampling
Total Cholesterol in mg/dl1 dayFasting blood sampling
LDL-Cholesterol in mg/dl1 dayMetabolic assessment (fasting blood sampling)
HDL-Cholesterol in mg/dl1 dayFasting blood sampling
Insulin in microU/ml1 dayFasting blood sampling
Lumbar bone mineralization in Tscore1 dayDual energy x-ray absorptiometry (DXA):
Femoral neck bone mineralization in Tscore1 dayDual energy x-ray absorptiometry (DXA):
Ovaries volume in ml1 dayPelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Ovaries follicles diameter in mm1 dayPelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Chronic anovulation in number1 dayNumber of mentruals cycles in a year
FSH in IU/L1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Oestradiol in ng/dl1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
DHEAS in micromol/l1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
17 hydroxyprogesterone in ng/ml1 dayMetabolic 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/ml1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Inhibine in pg/ml1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Prolactine in microgr/L1 dayMetabolic assessment (blood sampling before 10 am at the 2nd-5th day of the menstrual cycle or after 2 months of amenorrhea)
Uterine diameter in mm1 dayPelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Uterine volume in ml1 dayPelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Endometrius thickness in mm1 dayPelvic ultrasound (at 2nd-5th day of the menstrual cycle)
Total bone mineralization in Tscore1 dayDual energy x-ray absorptiometry (DXA):

Other

MeasureTime frameDescription
Quality of life1 daySelf-perception profile for adults, Messer & Harter 2012

Countries

Belgium

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026