Intracrinology: The New Science of Sex Steroid Physiology in Women

The control of DHEA action is completely different from that of E2 and testosterone, as engineered by the 500 million years of evolution which have added 30 or more intracrine enzymes controlling DHEA action in the human. In fact, the essential characteristics which differentiate the exposure to E2 and testosterone from the exposure to DHEA, an inactive compound by itself, derive from the major differences between endocrinology and intracrinology, which can be summarized as follows:The arrest of estrogen secretion by the ovaries at menopause causes an abrupt decrease of serum estradiol (E2) below the level of biological activity (established at 9.3 pg E2/ml (95th centile)), thus avoiding stimulation of the endometrium and decreasing the risk of endometrial cancer. As much as the arrest of E2 secretion by the ovaries is essential to protect the uterus, it is important that sex steroids continue to be available in the tissues other than the uterus where estrogens and androgens are needed for normal morphology and functioning. To this end, evolution, through 500 million years, has progressively provided the peripheral tissues with the sophisticated sets of enzymes which make androgens and estrogens from dehydroepiandrosterone (DHEA). The biologically inactive precursor DHEA appeared much later or approximately 20 million years ago with the primates. All elements were then in place for the installment of intracrinology or the cell-specific formation and inactivation of estrogens and androgens in peripheral tissues from the precursor DHEA, a molecule inactive by itself.