No abstract

Aromatase expression in the endometrium seems to play a pivotal role in the development of endometriotic lesions. Because inflammatory mediators such as prostaglandin E2 appear to activate aromatase in the cells of the endometrial stroma, it was hypothesised that the ensuing inflammation caused by the arrival of aromatase-positive cells in the peritoneal cavity would stimulate local estrogen production, which would in turn facilitate the development of endometriotic lesions by suppressing macrophage phagocytosis. Aromatase expression in the eutopic endometrium will also hamper ovum nidation, thus causing infertility. Progestins, such as gestodene and danazol, are potent inhibitors of aromatase expression in the endometrium, and the use of vaginal rings with danazol in doses that do not block ovulation is associated with the occurrence of pregnancy in patients with severe endometriosis without the need for surgery. A local effect on the endometrium suppressing aromatase expression has been suggested as a possible mechanism of action for the danazol ring.

Epigenetic changes favoring the transcription of the aromatase gene in the endometrium allow endometrial cells to survive in ectopic locations by producing estrogens that spare them from destruction through activated macrophages. Local estrogen production hastens prostaglandin synthesis by stimulating COX-2 activity, thus creating a self-perpetuating sequence of augmented estrogen formation and enhanced inflammation. Repetitive retrograde menstruation reintroduces aromatase-positive endometrial cells endowed with the capacity to implant and invade the peritoneum. In order to control endometriosis, an effective medication must inhibit aromatase, block COX-2, decrease fibrosis and induce amenorrhea. Within this framework, progestins, either alone or in the form of oral contraceptives, appear as first-line treatment for endometriosis owing to their capacity to block enzymes such as aromatase and COX-2.

BackgroundThe effect of resveratrol on the management of endometriosis-related pain was investigated in 12 patients who failed to obtain pain relief during use of an oral contraceptive containing drospirenone + ethinylestradiol.Methods and resultsThe addition of 30 mg of resveratrol to the contraceptive regimen resulted in a significant reduction in pain scores, with 82% of patients reporting complete resolution of dysmenorrhea and pelvic pain after 2 months of use. In a separate experiment, aromatase and cyclo-oxygenase-2 expression were investigated in the endometrial tissue of 42 patients submitted to laparoscopy and hysteroscopy for the management of endometriosis. Sixteen of these patients were using oral contraceptives alone prior to hospital admission, while the remaining 26 were using them in combination with resveratrol. Inhibition of both aromatase and cyclo-oxygenase-2 expression was significantly greater in the eutopic endometrium of patients using combined drospirenone + resveratrol therapy compared with the endometrium of patients using oral contraceptives alone.ConclusionThese results suggest that resveratrol potentiates the effect of oral contraceptives in the management of endometriosis-associated dysmenorrhea by further decreasing aromatase and cyclo-oxygenase-2 expression in the endometrium.

Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.