Aromatase Inhibitors: A Promising New Treatment For Endometriosis

Monday, April 27, 1998, Boca Raton, FL — The Endometriosis Research Center (ERC) recently announced valuable new research in the treatment of Endometriosis.

A team of researchers at the University of Texas Southwestern have found a promising new treatment for Endometriosis. In a preliminary study released in the April 1998 issue of Fertility and Sterility, Dr. Serdar E. Bulun and his team successfully treated a case of recurrent postmenopausal Endometriosis with Aromatase Inhibitors.

Last year, Dr. Bulun and his team found an unusual estrogen-synthesizing enzyme called Aromatase expressed in the endometrial tissue of women with Endometriosis. This enzyme allows the wayward tissues to implant on a woman's reproductive and nearby organs. In a further twist, the researchers uncovered that as this enzyme is induced by large amounts of inflammatory prostaglandins produced in the area, thus forming a vicious cycle to make its own estrogen and promote its own further growth.

Therefore, the research explains why despite surgery, hormone treatments and hysterectomies, many women continue to suffer with symptoms of Endometriosis such as severe recurrent pelvic pain. On the basis of these findings, the team conducted preliminary research on the use of Aromatase Inhibitors as a treatment for Endometriosis. According to the study, "The response to treatment in this case was strikingly successful, exemplified by the rapid disappearance of pelvic pain and near-complete eradication of a 30-mm vaginal endometriotic implant." Due to these promising results, Dr. Bulun and his team are conducting a nationwide study on the use of Aromatase Inhibitors as a treatment for recurrent, progressive Endometriosis.

Supported, in part, by an unrestricted grant from the American Society for Reproductive Medicine and Organon, Inc., the study raises important questions about the relationship of estrogen to Endometriosis.

OBGYN.net had the privilege of speaking with Dr. Serdar Bulun to get further information on his research and the current study. Dr. Andrew Cook, Medical Director for the Omega Ambulatory Surgical Institute, also addressed this issue in his "Ask Dr. Cook" column, which we have excerpted here.

OBGYN.net: Dr. Bulun, exactly what are Aromatase Inhibitors, and what they do in terms of Endo management and/or remission?

Dr. Serdar Bulun: Endometriosis is clearly an estrogen-dependent disease. Estrogen for Endometriosis is like fuel for fire. It has been classically assumed that estrogen is produced primarily in the ovaries of premenopausal women with Endometriosis, and thus GnRH agonists temporarily suppress Endometriosis in the majority but not all of these patients. Unfortunately, Endometriosis recurs in most of these patients treated with GnRH agonists. We recently demonstrated that estrogen is produced also in the endometriotic implants in the pelvis or other sites through the expression of the enzyme named Aromatase, i.e., estrogen synthase. Prostaglandins in endometriotic cells stimulate Aromatase activity to increase estrogen biosynthesis. In turn, estrogen stimulates prostaglandin formation and the growth of endometriotic implants. Thus, a positive feedback loop is formed and this favors continuous production estrogen in the endometriotic tissues. Aromatase Inhibitors break this cycle by blocking local production of estrogen in Endometriosis. They also decrease or block estrogen formation in other tissues, such as the ovary and subcutaneous fat.

OBGYN.net: How effective do you expect Aromatase Inhibitor treatment to be?

Dr. Serdar Bulun: It was extremely effective in a postmenopausal woman with an unusually aggressive form of recurrent Endometriosis. This woman had a hysterectomy and bilateral oophorectomy some 20 years ago. Thereafter, pelvic Endometriosis recurred many times, blocked a ureter and caused left renal atrophy. She had at least 3 laparotomies for resection of Endometriosis. The lesion was resistant to high-dose progestin treatment. A posterior exenteration was being considered. We elected to treat her with an Aromatase Inhibitor. Her severe pelvic pain decreased during the first month and completely disappeared from the second month on. During 9 months of treatment, the endometriotic lesion in her vagina was reduced from more than one inch to one tenth of an inch. We kept her on low dose Aromatase Inhibitor treatment from then on and she is still symptom-free after a total of 24 months of treatment.

Based on these observations, I expect that this new treatment will be very effective for Endometriosis in general.

OBGYN.net: How long until Aromatase Inhibitor treatment might be available to the general Endometriosis community?

Dr. Serdar Bulun: Not until randomized studies are completed. Possibly within a few years.

OBGYN.net: Who is a good candidate for this type of treatment? Is it for all AFS Stages of disease?

Dr. Serdar Bulun: I predict that this treatment can potentially be used for all stages of Endometriosis.

OBGYN.net: What are some side effects, if any, that your patients in the Aromatase Inhibitor study group have been reporting?

Dr. Serdar Bulun: Bone loss and hot flashes are the major side effects. These effects may be offset by concurrent use of bisphosphonates and clonidine.

OBGYN.net: Critics of Aromatase Inhibitors say that GnRH options are more effective, with less side effects. How would you address that?

Dr. Serdar Bulun: As indicated above, GnRH agonists block only ovarian estrogen secretion, whereas Aromatase Inhibitors stop estrogen biosynthesis in Endometriosis. They are two separate but related mechanisms. I predict that both drugs are important in treating Endometriosis.

OBGYN.net: What is the impact of Inhibitors on fertility?

Dr. Serdar Bulun: They may temporarily suppress ovulation or diminish egg quality, but these effects should be reversible.

OBGYN.net: Are you accepting any new patients into your team's research study at this time?

Dr. Serdar Bulun: Yes. We are conducting a large randomized study. We also treat women with Endometriosis resistant to other forms of treatment with Aromatase Inhibitors in a small compassionate use study.

OBGYN.net: Dr. Bulun, do you regard Inhibitors as the treatment of the future? Can Endometriosis patients look to this as the most effective option of management in the years to come?

Dr. Serdar Bulun: Aromatase Inhibitors are very powerful tools in the treatment of Endometriosis. Future studies will show whether they will be the most effective option or not.

OBGYN.net: Thank you, Dr. Bulun, for taking the time to speak with us. We are looking forward to future updates from your team on this promising new research.

If you are interested in joining Dr. Bulun's study, or would like additional information regarding his research, please contact him at:

Serdar E. Bulun, MD
Department of Obstetrics and Gynecology
Y.6.214A
UT Southwestern Medical Center
5323 Harry Hines Blvd
Dallas, TX 75235-9051
Tel: 214-648-4793
Fax: 214-648-8683