The Role of Aromatase in Endometriosis

Endometrial tissue from uterine disease-free women does not exhibit aromatase activity. In contrast, aromatase enzyme activity and mRNA levels are readily detectable in endometriosis. PGE2 stimulates both aromatase expression and activity in endometriotic stromal cells via promoter II region of the aromatase gene. This results in local production of estradiol, which induces PGE2 formation and establishes a positive feedback cycle. This mechanism seems to contribute to continuous local production of estradiol and PGE2.

ΑΙ (aromatase inhibitor) at typical dosages (for example, anastrozole 1 mg / day) reduces systemic estrogen levels in postmenopausal women by more than 85%. In premenopausal women, this effect is reduced by counter-regulation along the ovary-pituitary axis (i.e., the pituitary gland determining a decreased systemic estrogen level leads to sequential secretion of gonadotropins, which stimulate the synthesis of estrogen inhe ovaries and partially block the effect of ΑΙ, which leads to growth stimulation ovarian follicles. This also can lead to the formation of ovarian cysts.



In the past others have tried to use an intravaginal ring for the treatment of endometriosis with the controlled release of the Aromatase inhibitor anastrozole (PATENT EA 025582B1) with a daily release rate that does not induce stimulation of the ovaries by negative feed-back of the pituitary-ovarian-axis (which would cause secretion of gonadotropins and stimulation of ovarian follicular growth) and levonorgestrel in a daily release rate below the ovulation inhibition dose that provides contraceptive efficacy based on local effects (e.g. reducing and thickening of the cervical mucus impairing sperm ascension, effects on the endometrium and on tubal motility impairing implantation and egg transport). This approach has not resulted in a clinically useful treatment for endometriosis.