Aromataseinhibitoren bei Endometriose?

Zusammenfassung In Endometriosegewebe kommt es zu einer Überexpression der Aromatase. Die Aromataseüberexpression hat eine verstärkte lokale Östrogenbiosynthese zur Folge, die wiederum über die Hochregulation der Cyklooxygenase-2 (COX-2) eine Stimulation der Prostaglandin-E2-Produktion nach sich zieht. Dadurch entsteht eine Art positiver Feedbackmechanismus zwischen beiden Systemen. Außerdem wurde die Defizienz der 17β-Hydroxysteroiddehydrogenase-Type-II-Expression als eine weitere Abnormalität in Endometriosegeweben beschrieben, was die lokale Umwandlung von Östradiol in Östron erschwert. Diese beiden molekularen Aberrationen führen zu einer steigenden lokalen Konzentration von Östradiol und Prostaglandin E2. In verschiedenen menschlichen Zelllinien sind diese wiederum mit Zellproliferation, Migration, Angiogenese, Apoptoseresistenz und sogar Invasivität assoziiert. Konsequenterweise werden die Aromatase und die COX-2 als therapeutische Targets angesehen. Spezifische Aromataseinhibitoren oder selektive COX-2-Blocker sind viel versprechende Substanzen, die in kontrollierten klinischen Studien auf Sicherheit und Wirksamkeit bei Endometriose geprüft werden müssen, um das Spektrum der derzeit verfügbaren Therapieoptionen zu erweitern. Abstract Aromatase overexpression has been detected in endometriotic tissue. Aromatase activity gives rise to local estrogen biosynthesis, which in turn stimulates prostaglandin E2 production by upregulation of cyclooxygenase-2 (COX-2), thus establishing a positive feedback cycle. Another abnormality in endometriosis, i.e., the deficiency in 17ß-hydroxysteroid dehydrogenase type II (17ß-HSD type II) expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing amounts 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 promising new therapeutic targets. Specific aromatase inhibitors or selective COX-2 inhibitors are of great interest to be studied in clinical trials in premenopausal woman with endometriosis to extend the spectrum of currently available treatment options. Similar content being viewed by others Literatur Ailawadi R, Jobanputra S, Kataria M et al. (2004) Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 81:290–296 Alshafie GA, Abou-Issa HM, Seibert K, Harris RE (2000) Chemotherapeutic evaluation of celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model. Oncol Rep 7:1377–1381 Attia GR, Zeitoun K, Edwards D et al. (2000) Progesterone receptor isoform A but not B is expressed in endometriosis. 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Author information Authors and Affiliations Corresponding author Additional information Mit Unterstützung durch die Förderung des Stifterverbandes für die Deutsche Wissenschaft. Rights and permissions About this article Cite this article Ebert, A.D. Aromataseinhibitoren bei Endometriose?. Gynäkologische Endokrinologie 2, 208–215 (2004). https://doi.org/10.1007/s10304-004-0085-2 Issue date: DOI: https://doi.org/10.1007/s10304-004-0085-2