Higher Prepubertal IGF-1 Concentrations Associate to Earlier Pubertal Tempo in Both Sexes

Abstract

Introduction: Pubertal onset is triggered by multiple neuroendocrine interactions. The role of prepubertal IGF-1 in this process has not been explored in both sexes. Our objective is to analyze the association of prepubertal IGF-1 concentration with age at thelarche (B2) and menarche (M) in girls and age at gonadarche (G2) in boys. Methods: Longitudinal study (n=1196 boys and girls) within the Growth and Obesity Chilean cohort Study (GOCS). At ages ≈ 6.7 years blood sample for IGF-1. Subjects analyzed into 4 groups according to the onset age of the pubertal event. Results: Higher prepubertal IGF-1 levels were observed at earlier ages of thelarche (p=0.003) and menarche onset (p=0.041). A taller prepubertal height was observed at younger ages of thelarche and menarche (p=<0.001 and 0.002, respectively). The proportional hazard regression (HR) models showed that with an increase of 1 SD in IGF-1, the HR of presenting thelarche at younger ages was 1.25 and this association was maintained when adjusted for confounding variables. Similarly, the HR of presenting menarche at earlier ages was 1.21. This association was maintained only when adjusting for BMI but not using further confounders. In boys, prepubertal IGF-1 showed a tendency to be significantly higher in children with earlier gonadarche and taller height (both p<0.001). The HR of presenting gonadarche at younger ages was 1.22 and this association was maintained after adjusting for confounders. Conclusions: higher IGF-I levels in mid-childhood are associated with earlier puberty onset. The role of IGF-I in the onset of puberty requires further investigation.

Genetic correlation and Mendelian randomization analyses support causal relationships between dietary habits and age at menarche

“…IGF-1 levels are associated with age and play a key role in growth 68 . A few longitudinal studies have shown that higher IGF-1 levels are related to earlier puberty onset 69 and higher breast cancer risk 70 . Oily fish were positively associated with circulating IGF-I concentrations 71 .…”

Not Only Metabolic Complications of Childhood Obesity

“…On the other hand, GH secretion in individuals with obesity is reduced [ 95 ]. Interestingly, greater levels of IGF-1 before puberty were demonstrated to be associated with an earlier onset of thelarche and menarche among girls [ 96 ]. Similarly, higher growth before puberty was linked to lower ages of thelarche and menarche [ 96 ].…”

“…Interestingly, greater levels of IGF-1 before puberty were demonstrated to be associated with an earlier onset of thelarche and menarche among girls [ 96 ]. Similarly, higher growth before puberty was linked to lower ages of thelarche and menarche [ 96 ]. In the case of boys, higher pre-pubertal IGF-1 levels were associated with earlier gonadarche and increased height [ 96 ].…”

“…Similarly, higher growth before puberty was linked to lower ages of thelarche and menarche [ 96 ]. In the case of boys, higher pre-pubertal IGF-1 levels were associated with earlier gonadarche and increased height [ 96 ]. A German study found that children with obesity showed higher growth at birth than their normal-weight counterparts and had an accelerated growth rate thereafter, which was associated with increased levels of IGF-1, insulin, and leptin in these children [ 97 ].…”

IGF-1 and IGF-2 as Molecules Linked to Causes and Consequences of Obesity from Fetal Life to Adulthood: A Systematic Review

“…Children with obesity are usually taller than their normal-weight peers, which may be caused by increased circulating levels of IGF-1 [3,20,52,53], as GH release is suppressed, which implies that their height is rather GF-independent [20] or might be caused by increased adrenal androgens [54]. One study [30] reports the higher stature of obese children but also lower IGF-1 compared to a normal-weight control group.…”