Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women

Abstract

After cessation of estradiol secretion by the ovaries at menopause, the estrogens made by mechanisms of intracrinology are inactivated intracellularly at their site of formation and action, thus maintaining serum estradiol at biologically inactive concentrations to avoid stimulation of the endometrium. The absence of enzymes that are able to transform DHEA into estrogens in the endometrium explains the typical endometrial atrophy in all normal postmenopausal women in the presence of variable concentrations of circulating endogenous DHEA. According to these mechanisms, the inactive sex steroid precursor DHEA administered intravaginally acts exclusively in the vagina, whereas all serum sex steroids remain well within the biologically inactive postmenopausal reference range, thus avoiding any stimulation of the already atrophic endometrium.