Aromatase: A key molecule in the pathophysiology of endometriosis and a therapeutic target

Khaled M. Zeitoun, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

161 Scopus citations


Objective: To provide a clinically useful model illustrating the molecular aberrations affecting estrogen biosynthesis and metabolism in endometriosis and to discuss the therapeutic role of aromatase inhibitors. Design: Literature review. Result(s): Several molecular aberrations were found in endometriotic lesions (in contrast to eutopic endometrium) that favor increased local concentrations of E2. Endometriotic stromal cells aberrantly express aromatase, which converts C19 steroids to estrogens. Aromatase activity in these cells is stimulated by prostaglandin (PG)E2. Estrogen stimulates cyclooxygenase-2, giving rise to increased PGE2 formation. Thus, this positive feedback loop produces increasing quantities of E2 and PGE2 in endometriosis. The lack of aromatase expression in eutopic endometrium is maintained by binding of an inhibitory transcription factor, COUP-TF, to the aromatase promoter. In endometriosis, however, an aberrantly expressed factor, SF-1, displaces COUP-TF to bind to this same promoter and activates aromatase expression and thus local estrogen biosynthesis. Additionally, endometriotic glandular cells are deficient in 17β-hydroxysteroid dehydrogenase type 2, which converts E2 to estrone in the eutopic endometrium in response to P. Deficiency of this enzyme in endometriosis impairs the inactivation of E2 and may be a consequence of insensitivity to P. Conclusion(s): Molecular aberrations that increase local E2 concentrations may be important in the etiology of endometriosis. These molecules may be targeted to develop novel therapeutic strategies. The clinical relevance of aromatase expression in endometriosis was shown recently by the successful treatment of an unusually aggressive case of postmenopausal endometriosis with use of an aromatase inhibitor.

Original languageEnglish (US)
Pages (from-to)961-969
Number of pages9
JournalFertility and Sterility
Issue number6
StatePublished - Dec 1999


  • 17β- hydroxysteroid dehydrogenase type 2
  • Aromatase
  • Aromatase inhibitor
  • Endometriosis
  • Endometrium
  • Estrogen
  • Progesterone

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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