Arginase deficiency is an urea cycle disorder that generally presents with mental retardation and spasticity, yet uncommonly with episodes of hyperammonemia. A female adolescent with arginase deficiency developed hyperammonemic episodes temporally related to her menstrual cycle, which ceased upon adequate treatment with depot medroxy progesterone acetate. A similar case was previously reported. A catamenial trigger should be considered in adolescent female arginase-deficient patients with episodes of hyperammonemia.