Aromatase inhibitors and cyclooxygenase-2 (COX-2) inhibitors in endometriosis: new questions--old answers?
The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies for endometriosis-associated pain or recurrent disease are primarily aimed at downregulating ovarian function or antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is providing important results for the development of new, specific treatment modalities. Aromatase overexpression has recently been detected in endometriotic tissue. Aromatase (p450arom) is responsible for converting C19 androgens into estrogen in several types of human tissue. Aromatase activity causes local estrogen biosynthesis, which, in turn, stimulates prostaglandin E2 production by upregulating cyclooxygenase-2 (COX-2). Thus, a positive feedback cycle develops between the two systems. Another abnormality in endometriosis, the deficient 17beta-hydroxysteroiddehydrogenase type II (17beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations increase the amount of local estradiol and prostaglandin E2 in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance and even invasiveness. Consequently, aromatase and COX-2 are thought to be promising new therapeutic targets. Thus, specific aromatase inhibitors (e.g. Letrozol/Femara, Anastrozol/Arimidex or Exemestan/Aromasin) or selective COX-2 inhibitors (e.g. Celecoxib/Celebrex, Rofecoxib/Vioxx, Valdecoxib/Bextra) are of great interest and should be studied in clinical trials in premenopausal woman with endometriosis to expand the spectrum of currently available treatment options.
Ebert
Andreas D
AD
Charité Endometriosis Research Center Berlin, Department of Gynecology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. andreas.ebert@charite.de
Bartley
Julia
J
David
Matthias
M
D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism*; D004717:Endometrium / Q000201:enzymology; D005260:Female; D006801:Humans
D047072:Aromatase Inhibitors; D052246:Cyclooxygenase 2 Inhibitors