Correspondence

Endometriosis

N Engl J Med 1994; 330:70January 6, 1994

Article

To the Editor:

I was dismayed by the minimal discussion of potential side effects of therapy in the recent review article on endometriosis by Olive and Schwartz (June 17 issue)1. Although short-term use of gonadotropin-releasing hormone (GnRH) agonists is associated with a reversible decline in bone mineral density,2 long-term therapy could lead to a sustained loss of bone. Low bone density is one of the major risk factors for osteoporosis, a disease that affects many women at great expense to society in terms of medical costs and decreased quality of life3,4. Treatment of endometriosis with GnRH agonists has become popular despite the availability of equally efficacious and bone-neutral drugs1; without adequate monitoring for skeletal side effects, women who currently have endometriosis may needlessly be put at risk for osteoporosis later in life.

If it is determined that a GnRH agonist is the best treatment for a particular patient's endometriosis, measurements of bone mineral density at base line and during treatment (dual-energy x-ray absorptiometry is very precise5) would permit the longitudinal evaluation of skeletal changes, so that providers and patients could make informed decisions about the long-term costs and benefits of GnRH-agonist therapy.

Marie Luz Villa, M.D.
Stanford University School of Medicine, Palo Alto, CA 94304

5 References

1. 1

   Olive DL, Schwartz LB. Endometriosis. N Engl J Med 1993;328:1759-1769
   Full Text | Web of Science | Medline

2. 2

   Whitehouse RW, Adams JE, Bancroft K, Vaughan-Williams CA, Elstein M. The effects of nafarelin and danazol on vertebral trabecular bone mass in patients with endometriosis. Clin Endocrinol (Oxf) 1990;33:365-373
   CrossRef | Web of Science | Medline

3. 3

   Chesnut CH III. Osteoporosis and its treatment. N Engl J Med 1992;326:406-408
   Full Text | Web of Science | Medline

4. 4

   Cummings SR, Kelsey JL, Nevitt MC, O'Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 1985;7:178-208
   Web of Science | Medline

5. 5

   Wahner HW, Dunn WL, Brown ML, Morin RL, Riggs BL. Comparison of dual-energy x-ray absorptiometry and dual photon absorptiometry for bone mineral measurements of the lumbar spine. Mayo Clin Proc 1988;63:1075-1084
   Web of Science | Medline

Author/Editor Response

Dr. Olive replies:

To the Editor: I would like to thank Dr. Villa for her comments expanding on the effects of GnRH agonists on bone mineral density. She correctly points out that whereas short-term use “is associated with a reversible decline in bone mineral density, long-term therapy could lead to a sustained loss of bone.” The source of her concern that women with endometriosis who are treated with GnRH agonists “may needlessly be put at risk for osteoporosis later in life” is unclear, however.

The recommended course of GnRH-agonist treatment is up to six months; bone loss over this period has been demonstrated to be reversible when the medication is discontinued1. There are no data to suggest that measurements of bone mineral density at base line and during treatment are either informative or cost effective in women so treated; in fact, given the apparently reversible nature of the bone loss, I would not expect such studies to be of value.

The use of GnRH agonists for longer periods, however, raises a different issue. Such use is clearly contraindicated in the absence of monitoring of bone mineral density. Recent attempts to eliminate the decline in bone mass with long-term treatment have involved the addition of small doses of estrogen,2 sodium etidronate,3 or clomiphene (unpublished data) to GnRH-agonist therapy. These so called “add-back” regimens seem to be effective in maintaining bone density despite long-term exposure to GnRH agonists. Since such regimens are still in the investigational stage, however, monitoring of bone mineral density is an integral aspect of such studies.

It is clear that when using these medications, the clinician should keep in mind the potential for adverse effects on bone. If a woman at high risk for such side effects should need treatment for endometriosis, the astute clinician should be alert to options for monitoring bone loss or even the use of alternative drugs. A blanket request for bone-mineral evaluation in all patients treated with GnRH agonists, however, is justified neither scientifically nor -- given the current climate regarding health care reform -- financially.

David L. Olive, M.D.
Yale University School of Medicine, New Haven, CT 06510

3 References

1. 1

   Dodin S, Lemay A, Maheux R, Dumont M, Turcot-Lemay L. Bone mass in endometriosis patients treated with GnRH agonist implant or danazol. Obstet Gynecol 1991;77:410-415
   Web of Science | Medline

2. 2

   Barbieri RL. Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol 1992;166:740-745
   Web of Science | Medline

3. 3

   Surrey ES, Fournet N, Voigt B, Judd HL. Effects of sodium etidronate in combination with low-dose norethindrone in patients administered a long-acting GnRH agonist: a preliminary report. Obstet Gynecol 1993;81:581-586
   Web of Science | Medline