Taken together, the results suggest that INSL3 represents a new and important independent parameter with which to identify primary Leydig cell insufficiency and hence primary hypogonadism, and complementing the use of LH and/or T, which may be subject to influences at central/hypothalamic, pituitary, or on feedback systems. This evidence concerns the gene PLOD1 and Hypergonadotropic hypogonadism.