Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists
- Mark D Hornstein, MD
Mark D Hornstein, MD
- Professor of Obstetrics, Gynecology & Reproductive Biology
- Harvard Medical School
- William E Gibbons, MD
William E Gibbons, MD
- Division of Reproductive Endocrinology
- Department of Obstetrics and Gynecology
- Baylor College of Medicine
- Chief of Reproductive Medicine for the Pavilion for Women
- Texas Children's Hospital
Pelvic pain due to endometriosis can be treated with medical therapy, surgical intervention, or a combination of both. In most cases, women with chronic pelvic pain (CPP) thought to be due to endometriosis are initially treated empirically with nonsteroidal anti-inflammatory drugs (NSAIDS) and combined estrogen-progestin contraceptives. (See "Treatment of chronic pelvic pain in women".)
If these medications do not resolve the pain, laparoscopy is usually performed to determine a definitive diagnosis. If the diagnosis of endometriosis is confirmed at laparoscopy, conservative surgery involving excision, fulguration, or laser vaporization of endometriotic implants and adhesiolysis is often attempted. (See "Endometriosis: Surgical management of pelvic pain".)
Pain can continue after conservative surgery. Recurrence of endometriosis is estimated as 21.5 percent at two years and 40 to 50 percent at five years after surgery . For women with persistent pain or selected patients who have not responded to empiric treatment with NSAIDs or oral contraceptives , administration of a gonadotropin releasing hormone (GnRH) agonist is usually effective.
Side effects of GnRH agonists, such as vasomotor symptoms and accelerated bone loss, limit treatment duration to six months. However, treatment can be extended beyond six months if add-back therapy is combined with the GnRH agonist.
BASIS FOR HORMONAL TREATMENT
Compared to eutopic endometrium, endometriotic implants are characterized by overproduction of prostaglandins and local production of estrogens and cytokines, which synergize the activities of each other, promote implantation of ectopic endometrium, and cause the pain associated with endometriosis . In addition, aromatase overactivity results in increased COX2 expression favoring prostaglandin E production, which, in turn, upregulates estrogen synthesis pathways. Interventions that reduce ovarian estrogen production reduce this synergistic process, thereby reducing or eliminating endometriosis-related pain. (See "Endometriosis: Pathogenesis, clinical features, and diagnosis".)
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- BASIS FOR HORMONAL TREATMENT
- PHARMACOLOGY OF GnRH AGONISTS
- Side effects
- Gonadotropin releasing hormone agonists after conservative surgery
- Recurrence of symptomatic endometriosis
- Symptomatic rectovaginal endometriosis
- GnRH WITH ADD-BACK THERAPY
- GnRH antagonists
- - Progestin-only add-back
- - Estrogen plus progestin add-back
- - Nonsteroidal add-back
- - Other
- Concurrent versus delayed initiation of hormonal add-back
- Duration of therapy
- LOW DOSE GNRH
- Titration method
- Longer interval method
- Addition of an aromatase inhibitor
- SUMMARY AND RECOMMENDATIONS