Coincident events of progesterone withdrawal and hypoxia. Progesterone withdrawal results in an up-regulation of inflammatory mediators, production of MMPs, a leukocyte influx and expression of stromal KDR in the upper endometrial zones. There is coincident hypoxia and an up-regulation of VEGF. VEGF binds to its type 2 receptor, KDR and there is a paracrine/autocrine action on the up-regulation of MMP production in the same endometrial upper zone stromal cells. Menstrual sloughing takes place from the superficial regions of the endometrium. Reproduced with permission.