the combination with TFE and TIFL may significantly prevent increased levels of FSH and LH induced by sex hormone deficiency and stimulate the secretion of GnRH, which indicated that regulation of related hormones at each level of hypothalamic-pituitary-gonad axis could be one of the pharmacological mechanisms of the combination with TFE and TIFL for osteoporosis treatment. Here, PLOD1 is linked to osteoporosis.