Correspondence

Endometriosis

N Engl J Med 2009; 360:1911-1912April 30, 2009

Article

To the Editor:

In the review article on endometriosis, Bulun (Jan. 15 issue)1 states that the presence of aromatase in endometriotic lesions appears to play an important role in the production of estradiol, and it is considered to be a key factor for endometrial proliferation.

However, Delvoux et al. recently reported the absence of aromatase activity in endometriotic lesions,2 and we also did not detect aromatase protein in the glandular and stromal compartments of ectopic endometrial tissue. We recently found that what was believed to be aromatase protein was mainly endogenous biotin labeling or iron deposits.3 Using three different protocols, we found only barely detectable amounts of aromatase messenger RNA (mRNA). Among 21 peritoneal endometriotic lesions, 16 were aromatase-negative and 5 were near the limit of detection. Our results suggest that aromatase produced within endometriotic lesions might not be as important in endometriosis as postulated in Bulun's review.

Sébastien Colette, Ph.D.
Jacques Donnez, M.D., Ph.D.
Université Catholique de Louvain, 1200 Brussels, Belgium
jacques.donnez@uclouvain.be

3 References

1. 1

   Bulun SE. Endometriosis. N Engl J Med 2009;360:268-279
   Full Text | Web of Science | Medline

2. 2

   Delvoux B, Groothuis P, D'Hooghe T, Kyama C, Dunselman G, Romano A. Increased production of 17beta-estradiol in endometriosis lesions is the result of impaired metabolism. J Clin Endocrinol Metab 2009;94:876-883
   CrossRef | Web of Science | Medline

3. 3

   Colette S, Lousse JC, Defrère S, et al. Absence of aromatase expression in human peritoneal, ovarian and rectovaginal endometriotic lesions. Presented at the 10th World Congress on Endometriosis, Melbourne, Australia, March 11–14, 2008. poster.
   

Author/Editor Response

Biologically relevant levels of aromatase and its product estradiol in vertebrate tissues are lower by a factor of 100 to 100,000 than the levels of most other steroidogenic proteins and their products. Thus, the accurate evaluation of aromatase expression and enzyme levels in extraglandular cells and tissues is a complex task and requires a laboratory with substantial expertise and experience in making such measurements. Since the mid-1990s, several laboratories in various parts of the world have consistently reported aromatase mRNA and enzyme activity in endometriotic tissues and cells.1-4 My colleagues and I have reported the presence of aromatase in endometriosis, and we have described the signaling pathway responsible for coordinated induction of aromatase and other steroidogenic genes required for the production of estradiol from cholesterol in endometriotic tissue.1 The letter by Colette and Donnez contradicts their recently published article in which they reported that aromatase mRNA was detected in all but 2 of the approximately 60 samples of ovarian, peritoneal, and deep endometriotic tissues they studied.5

Serdar E. Bulun, M.D.
Northwestern University, Chicago, IL 60611
s-bulun@northwestern.edu

5 References

1. 1

   Attar E, Tokunaga H, Imir G, et al. Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab 2009;94:623-631
   CrossRef | Web of Science | Medline

2. 2

   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

3. 3

   Kyama CM, Overbergh L, Mihalyi A, et al. Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis. Fertil Steril 2008;89:301-310
   CrossRef | Web of Science | Medline

4. 4

   Matsuzaki S, Canis M, Pouly JL, Dechelotte PJ, Mage G. Analysis of aromatase and 17beta-hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid expression in deep endometriosis and eutopic endometrium using laser capture microdissection. Fertil Steril 2006;85:308-313
   CrossRef | Web of Science | Medline

5. 5

   Heilier JF, Donnez O, Van Kerckhove V, Lison D, Donnez J. Expression of aromatase (P450 aromatase/CYP19) in peritoneal and ovarian endometriotic tissues and deep endometriotic (adenomyotic) nodules of the rectovaginal septum. Fertil Steril 2006;85:1516-1518
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Britton Trabert, Stephen M. Schwartz, Ulrike Peters, Anneclaire J. De Roos, Chu Chen, Delia Scholes, Victoria L. Holt. (2011) Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an evaluation of candidate genes. Fertility and Sterility 96:6, 1401-1406.e3
   CrossRef

2. 2

   S. Colette, S. Defrere, J. C. Lousse, A. Van Langendonckt, J. P. Gotteland, E. Loumaye, J. Donnez. (2011) Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model. Human Reproduction 26:6, 1362-1370
   CrossRef

3. 3

   P. Vercellini, P. Crosignani, E. Somigliana, P. Vigano, M. P. Frattaruolo, L. Fedele. (2011) 'Waiting for Godot': a commonsense approach to the medical treatment of endometriosis. Human Reproduction 26:1, 3-13
   CrossRef