The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer

Postmenopausal estrogens originate from the peripheral conversion of androgens, which are produced by the adrenal glands and the ovaries. Estrogens are considered to contribute to the neoplastic development of endometrium. Hyperplasia of ovarian stroma is associated with an increased androgen production by the ovaries and with the development of endometrial pathology. We hypothesize that, in cases of endometrial pathology, an increased production of aromatizable androgens by postmenopausal ovaries will lead to elevated prehormone availability for estrogen formation in utero. Following the conversion of ovarian androgens, a reaction catalyzed by the cytochrome P450 aromatase, estrogens may function as a local mitogenic factor eventually leading to the development of endometrial cancer. We consider the local availability of androgens and the local activity of aromatase relevant for this process. If this hypothesis proves to be right it may give rise to the introduction of aromatase inhibitors in treatment strategies of hormone dependent endometrial malignancies.