Part of “CHAPTER 98 – ENDOMETRIOSIS“

Suppression of ovarian estrogen production is the most reliable method for causing the regression of endometriosis lesions. For many years, surgical oophorectomy has been the main option for permanently reducing ovarian estrogen production. Long-term improvement in pelvic pain caused by endometriosis occurs in ˜90% of women who have a bilateral oophorectomy.18 In the United States, endometriosis is the second most common indication for hysterectomy and oophorectomy. For young women who have not completed their families, bilateral oophorectomy is not a good option. The gonadotropin-releasing hormone (GnRH) analogs—which can reversibly suppress ovarian estrogen production—have become the mainstay for the treatment of pelvic pain caused by endometriosis.

GnRH agonists are analogs of the native decapeptide, GnRH, with chemical changes in amino acids 6 and 10. The introduction of D-amino acids at position 6 of native GnRH can result in GnRH agonist analogs that are resistant to degradation by endopeptidases (and thus have long half-lives), have high affinity for the GnRH receptor, and have long receptor occupancy.19 Paradoxically, initial treatment with a GnRH
analog stimulates LH and FSH secretion, but prolonged treatment suppresses it (greater for LH than for FSH). The suppression of secretion results in suppression of ovarian follicle growth and a 95% decrease in estrogen production; the circulating estradiol concentration is in the range of that observed in menopausal women (15 pg/mL) (Table 98-2). Studies of surgical staging of endometriosis lesions before and after treatment with a GnRH analog demonstrated that serum estradiol levels in the range of 15 pg/mL reliably cause them to atrophy. In these studies, GnRH analogs produce significant decrease in pelvic pain in 85% of treated women and reduce the number and size of endometriosis implants.20,21,22 and 23