The relationship between the extraglandular production of estrone and the occurrence of endometrial neoplasia

In a series of studies involving the determination of the mechanism(s) of estrogen production in women with endometrial neoplasia, it has been ascertained that the estrogenic hormonal milieu of endometrial adenocarcinoma is the near-exclusive production at extraglandular site(s) of the estrogen product hormone, estrone from the aromatization of plasma androstenedione. Further, the results of these studies indicate that those metabolic aberrations which give rise to the capability for increased extraglandular estrone production are precisely the same as those constitutional stigmata and/or ovarian abnormalities that are known to be associated with an increased incidence of endometrial neoplasia. Increased estrone production at extraglandular site(s) occurs as a consequence of one of two events; i.e., increased availability of the plasma precursor, androstenedione, or increased extent of conversion of the plasma precursor, androstenedione, to its product hormone, estrone at extraglandular site(s). Thus, a hypothesis has emerged which relates the estrogenic hormonal milieu of near-exclusive estrone production to the occurrence of endometrial neoplasia and suggests that those constitutional stigmata which are associated with an increased occurrence of endometrial neoplasia are identical with those that give rise to metabolic mechanism(s) for increasing extraglandular estrone production.