The science of local sex steroid synthesis in peripheral tissues from inactive precursors such as DHEA
Before menopause, estrogens come from two sources, namely the ovaries, as an essential component of reproduction, and the adrenals which secrete DHEA, an inactive compound in itself transformed inside the peripheral tissue cells into cell-specific amounts of estrogens and androgens.
At menopause, the secretion of estrogens stops while the secretion of DHEA, which started decreasing earlier at the age of 30, continues to decrease during the following years. Most importantly, after menopause, only DHEA remains as the main source of both estrogens and androgens. During the postmenopausal years, the rapidly decreasing serum levels of DHEA cause a parallel decrease of androgens and estrogens in peripheral tissues.
In both men and women, DHEA is circulating at a high level throughout life, even though it decreases with age. More than 35 enzymes were identified and permit the metabolization of DHEA into active sex steroids. These enzymes were shown to be expressed in many peripheral tissues, including in the vaginal mucosa. Intracrinology is a multistep process essentially controlling the transformation of DHEA exclusively inside the cells, thus not significantly contributing to the circulating levels of estrogens and androgens.