Influence of Early Adiposity Rebound, Genetic Polymorphisms and GnRHa Treatment on Long-term Outcome of Girls With Idiopathic Central Precocious Puberty.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 418
- 试验地点
- 2
- 主要终点
- Single nucleotide polymorphisms (SNP) analyses
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Single nucleotide polymorphisms (SNP) analyses
时间窗: 1 day
DNA analyses
次要结局
- Lumbar bone mineralization in Tscore(1 day)
- Body composition in %(1 day)
- LDL-Cholesterol in mg/dl(1 day)
- Adult height in meters(1 day)
- Total Cholesterol in mg/dl(1 day)
- Abdominal perimeter in cm(1 day)
- LH in IU/L(1 day)
- Prolactine in microgr/L(1 day)
- Endometrius thickness in mm(1 day)
- Body mass index in kg/m2(1 day)
- Glucose in mg/dl(1 day)
- Insulin in microU/ml(1 day)
- Femoral neck bone mineralization in Tscore(1 day)
- SHBG by nmol/l(1 day)
- Hip perimeter in cm(1 day)
- Blood pressure in mmHg(1 day)
- 17 hydroxyprogesterone in ng/ml(1 day)
- Ovaries volume in ml(1 day)
- Ovaries follicles counting(1 day)
- Oestradiol in ng/dl(1 day)
- DHEAS in micromol/l(1 day)
- Inhibine in pg/ml(1 day)
- Uterine diameter in mm(1 day)
- Uterine volume in ml(1 day)
- HDL-Cholesterol in mg/dl(1 day)
- Total bone mineralization in Tscore(1 day)
- Chronic anovulation in number(1 day)
- Testicular volume in ml(1 day)
- FSH in IU/L(1 day)
- Anti-Müllerian Hormone in ng/ml(1 day)
- Ovaries follicles diameter in mm(1 day)
- Total serum testosterone by ng/dl(1 day)