Hormone Treatment of Endometriosis: the Estrogen Threshold Hypothesis

In women with recurrent pelvic pain caused by endometriosis, hormonal therapy with a gonadotropin-releasing hormone agonist is an effective alternative to surgical therapy. The basis for medical treatment of endometriosis is that endometriosis lesions are dependent on estradiol for continued growth. Further, end organ tissue varies in its sensitivity to estradiol. This forms the basis of the estrogen threshold hypothesis, that is, that a concentration of estradiol that will partially prevent bone loss may not stimulate endometrial growth. Thus there is a hierarchy of organ response to estradiol such that calcium metabolism is most sensitive followed by gonadotropin secretion, vaginal epithelial growth, lipid metabolism, and liver protein production. Similarly, breast cancer is most sensitive and endometriosis is least sensitive to estrogen. These differences may allow the design of regimens with a gonadotropin-releasing hormone agonist that maintain a therapeutic response and ameliorate potential adverse effects.