Synthetic progestins occupy progesterone receptors and thereby block progesterone function. Being foreign to human metabolism, they are less readily metabolized and excreted. Some progestins may also bind to testosterone or estrogen receptors, unlike real progesterone. Progesterone receptors exist in almost all tissues of the body including the brain, connective tissue, the immune system, mucosal cells, hair follicle cells, all the sex glands, Schwann cells, etc. When progesterone bonds with its receptor in target tissues it enters the cell nucleus to activate specific genes for specific cell functions.
Progesterone is a specific molecule.
Its action is a result of its specific molecular configuration. Progesterone participates within a complex hormonal network that includes cortisol, all the various estrogens, testosterone and thyroid as well as hypothalamic feed-back centers. Synthetic progestins disrupt this complex hormonal network. They will never fulfill the role of real progesterone in human metabolism. When Dr. Pike claims that progestins may increase breast cell proliferation and the risk of breast cancer, he is speaking of synthetic progestins, and not progesterone.