REVIEW Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance

Conversion of C19 steroids to estrogens is catalyzed by aromatase in human ovary, placenta and extraglandular tissues such as adipose tissue, skin and the brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2 (PGE2). This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient hydroxysteroid dehydrogenase (17-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quan-tities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.