Most women with PCOS exhibit elevated basal LH levels due to accelerated episodic release of pituitary LH [136], and thus likely hypothalamic GnRH, increased pituitary LH responsiveness to GnRH [146,147], and diminished negative feedback efficacy of both E2 and P4 [137,138], with such neuroendocrine abnormalities arising during adolescence [18,139]. This evidence concerns the gene PLOD1 and polycystic ovary syndrome.