Correspondence

Gonadotropin-Releasing Hormone Agonists for Endometriosis

N Engl J Med 2008; 359:2844-2845December 25, 2008

Article

To the Editor:

In his article on gonadotropin-releasing hormone (GnRH) agonists as a treatment for endometriosis, Olive (Sept. 11 issue)1 describes a 36-year-old woman with pelvic pain who did not have a response to hormonal treatment initiated on a presumption of endometriosis. In our view, all medical treatments resulting in suppression of ovarian function are equally effective for treating endometriosis.2 Hence, the failure of one treatment constitutes reasonable grounds for recommending surgery, which is of proven efficacy for providing lasting relief of pelvic pain.3 Surgery may also prevent disease extension and its possible toll on fecundity.4

When surgery is contraindicated, it may be appropriate to revert to other treatments, such as the use of aromatase inhibitors in association with ovarian blockade with oral contraceptives. This approach aims at blocking not just ovarian function but also the local in situ production of estrogen identified in endometriotic implants and eutopic endometrium.5 Although aromatase inhibitors must be handled by experts only (and their use for this application has not been approved by the Food and Drug Administration), they are the only alternative that is possibly superior to ovarian blockade alone.6

Dominique de Ziegler, M.D.
Bruno Borghese, M.D.
Charles Chapron, M.D.
Cochin University Hospital, 75014 Paris, France
dominique.deziegler@svp.aphp.fr

6 References

1. 1

   Olive DL. Gonadotropin-releasing hormone agonists for endometriosis. N Engl J Med 2008;359:1136-1142
   Full Text | Web of Science | Medline

2. 2

   Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005;20:2698-2704
   CrossRef | Web of Science | Medline

3. 3

   Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steril 1994;62:696-700
   Web of Science | Medline

4. 4

   Chapron C, Fritel X, Dubuisson JB. Fertility after laparoscopic management of deep endometriosis infiltrating the uterosacral ligaments. Hum Reprod 1999;14:329-332
   CrossRef | Web of Science | Medline

5. 5

   Bukulmez O, Hardy DB, Carr BR, Word RA, Mendelson CR. Inflammatory status influences aromatase and steroid receptor expression in endometriosis. Endocrinology 2008;149:1190-1204
   CrossRef | Web of Science | Medline

6. 6

   Nawathe A, Patwardhan S, Yates D, Harrison GR, Khan KS. Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG 2008;115:818-822[Erratum, BJOG 2008;115:1069.]
   CrossRef | Web of Science | Medline

Author/Editor Response

Although many drugs suppress ovarian function, they do so to varying degrees. The profound hypoestrogenism of GnRH agonists has been compared with the euestrogenic inhibition of ovulation seen with oral contraceptives in two randomized trials, in which the GnRH agonist was found to produce significantly better pain relief in one or more end points.1,2 Furthermore, similar effectiveness of comparators used for primary therapy does not rule out a drug's value in sequential therapy. In a randomized trial by Ling,3 the majority of patients who did not have pain relief with oral contraceptives had a successful response to a GnRH agonist.

Surgery, while proven efficacious, has been randomly compared with the use of a GnRH agonist and has been shown to be less effective.4 Finally, the suggestion that aromatase inhibitors with oral contraceptives should be the next medical step is unfounded, since no randomized trials have compared this regimen with any other. The recommendation of surgery or aromatase inhibitors as the next intervention is not based on a reading of the best available evidence.

David L. Olive, M.D.
Wisconsin Fertility Institute, Middleton, WI 53562
dlolive1@aol.com

Since publication of his article, Dr. Olive reports receiving consulting fees from Novartis.

No further potential conflict of interest relevant to this letter was reported.

4 References

1. 1

   Vercellini P, Trespidi L, Colombo A, Vendola N, Marchini M, Crosignani PG. A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril 1993;60:75-79
   Web of Science | Medline

2. 2

   Zupi E, Marconi D, Sbracia M, et al. Add-back therapy in the treatment of endometriosis-associated pain. Fertil Steril 2004;82:1303-1308
   CrossRef | Web of Science | Medline

3. 3

   Ling FW. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Obstet Gynecol 1999;93:51-58
   CrossRef | Web of Science | Medline

4. 4

   Zupi E, Sbracia M, Marconi D, Sorrenti G, Zullo F, Polumba S. Role of medical therapy in the treatment of endometriosis associated pelvic pain: a randomized controlled study. J Minim Invasive Gynecol 2005;12:Suppl:6-6
   CrossRef | Web of Science | Medline