INS and Insulin resistance: The causal relationship is still uncertain, but supporting the role of insulin resistance in early menarche are the clinical studies of Ibañez et al. Focusing on girls born small for gestational age (SGA) experiencing early puberty, they revealed that treatment with metformin, which enhances insulin sensitivity, delayed pubertal progression and age at menarche by nearly 1 year compared to the untreated group [38].