-Estrogen Deficiency: Insufficient steroid precursors (e.g., in severe FAO or GSD) can reduce estrogen levels, impairing bone health and pubertal progression.-Insulin Sensitivity Loss: When estrogen production is perturbed, beneficial effects on insulin signaling and lipid metabolism are diminished.-Increased CV Risk: Loss of estrogen’s anti-inflammatory influence can raise the risk of vascular complications (e.g., endothelial dysfunction in PKU). This evidence concerns the gene INS and endothelial dysfunction.