Aromatase inhibitors: A promising new treatment for endometriosis

02/10/04

Northwestern Memorial Hospital physician publishes findings of pioneering study in February issue of Fertility and Sterility

Letrozole (Femara), an aromatase inhibitor currently used to prevent breast cancer recurrence in postmenopausal women, shows promise in the treatment of endometriosis, according to the results of a pioneering pilot study conducted by Serdar Bulun, M.D., chief of the Division of Reproductive Biology Research at Northwestern Memorial Hospital. His findings were published in the February issue of Fertility and Sterility.

"This study demonstrates the potential of aromatase inhibitors to significantly and rapidly reduce disease severity and pain, offering women a new and more effective way of suppressing endometriosis with fewer side effects," explains Dr. Bulun. "Endometriosis is caused when tissue similar to the lining of the uterus grows elsewhere in the body and affects about 10 to 15 percent of women of reproductive age. It causes chronic pelvic pain and contributes to infertility."

Within the past 10 years, the research team led by Dr. Bulun pioneered the molecular model that the aromatase enzyme, which produces estrogen, is present in the endometrial tissue of women with endometriosis. His team discovered that this enzyme is able to reproduce itself, creating a vicious cycle of estrogen production.

"This explains why despite surgery, hormone treatments and hysterectomies, many women continue to suffer with symptoms of endometriosis," explains Dr. Bulun. "Endometriosis is an estrogen-dependent disease, so estrogen for endometriosis is like fuel for fire. We need to attack the root problem the aromatase in order to eliminate this cycle, halt the local production of estrogen and treat women with this disease."

Dr. Bulun evaluated 10 patients with moderate to severe endometriosis, all previously treated both medically and surgically with unsatisfactory results. Each of these patients took letrozole, along with progestin, for six months. Dr. Bulun evaluated the endometriosis objectively by performing laparoscopy a surgical endoscopic procedure to visualize the pelvic structures at the beginning and end of the study. In all patients, a second-look laparoscopy showed the endometriosis had either disappeared or was strikingly reduced.

The study also showed a very significant reduction in pain associated with endometriosis. Nine out of 10 patients reported significant pelvic pain relief, as measured by the American Society for Reproductive Medicine (ASRM) scores for endometriosis and pelvic pain assessed by visual analog scale. The mean score for pretreatment pain was 6.22 out of a maximum of 10. After treatment, the mean score was reduced to 2.52.

Currently, one of the most commonly used treatments for endometriosis are Gonadotropin-releasing hormone (GnRH) analogues, a group of drugs that decrease the production of estrogen to the levels a woman has after menopause; however, these drugs have unpleasant side effects, such as bone loss, and can only be used for a short period of time. Surgical options also exist, but symptoms of endometriosis return rapidly in more than 50% of women who undergo surgery.

Study participants also took calcium citrate and vitamin D to reduce the risk of bone loss. Overall, no significant change in bone density was detected.

The most common side effects were occasional irregular bleeding and mild hot flashes, which were tolerated well.

"These results appear extremely promising and constitute the rationale for further investigation of this regimen as a first-line treatment for endometriosis," said Dr. Bulun.

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Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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