Intracrinology and menopause: the science describing the cell-specific intracellular formation of estrogens and androgens from DHEA and their strictly local action and inactivation in peripheral tissues

Abstract

The secretion of estrogens by the ovaries stops at menopause. Afterward, dehydroepiandrosterone (DHEA) becomes the only source of both estrogens and androgens during all the postmenopausal years. To maintain very low and biologically inactive concentrations of estrogens and androgens in the circulation, DHEA is transformed intracellularly into cell-specific small amounts of estrogens and androgens (except in the endometrium) which then act and are inactivated locally in the same cells, thus avoiding biologically significant systemic exposure to active sex steroids. The secretion of DHEA, however, mainly of adrenal origin, has already decreased by an average of 60% at the time of menopause and it continues to decrease thereafter with a parallel lowering in available intracellular estrogens and androgens. Consequently, after the arrest of estrogen secretion by the ovaries, the loss of DHEA becomes practically responsible for the symptoms and signs of menopause. Replacing what is missing, namely DHEA, at the right place, at the right time, and in the right amount, seems to be the logical and physiological approach for the treatment of menopausal symptoms and signs, as recently demonstrated for pain at sexual activity (dyspareunia), the most bothersome symptom of vulvovaginal atrophy due to menopause.