THERAPUETIC APPLICATION OF AROMATASE INHIBITOR FOR LEIOMYOMA OF THE UTERUS AND ENDOMETRIOSIS

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1. Leiomyoma of the uterus expresses estrogen synthetase (aromatase) and synthesize estrogen in situ. Preoperative GnRH agonist therapy abolishes aromatase expression in leiomyoma tissues in situ in addition to aromatase expression in the ovary. This combined suppression may explain why GnRH agonists induced shrinkage of leiomyoma more rapidly and more profoundly than natural menopause.2. Addition of androstenedione stimulates cell proliferation of leiomyoma cells in culture. This growth stimulatory action was completely canceled by the pretreatment with an aromatase inhibitor (fadrozole).3. Oral administration of fadrozole (1mg/kg/day,>1 weeks) induced anovulatory state in rats. Estrus cycles were recovered within 1 week after the discontinuation of fadrozole.4. Oral fadrozole (2mg/day) induced rapid and profound regression of leiomyoma and resolved bulk-related symptoms of a perimenopausal woman. The potential uses of aromatase inhibitors was demonstrated.5. AF-1/AD4BP binds to a nuclear half site of the most proximal promoter of aromatase (PII) and up-regulates the transcription of aromatase in endometriosis cells. Cis elements of PII promoter of aromatase, therefore its regulation, were quite different between endometriosis and the ovary, suggesting that tissues-specific and promoter-specific modulation of aromatase expression is possible.