Alleviating the "ouch" of endometriosis

Aromatase inhibitor letrozole could offer relief to sufferers

By Maria Turner

In 1998 a post-menopausal woman presented in Dr Serdar E Bulun's office with a severe case of endometriosis. Dr Bulun is the chief of the Division of Reproductive Biology Research at Northwestern Memorial Hospital in Chicago. The woman continued to suffer from the disease despite a complete hysterectomy and the removal of both of her ovaries. "Her disease was life-threatening," said Dr Bulun. "She lost one of her kidneys. We hypothesized that local aromatase, present in the endometriosis lesions, was what was driving the disease. So we targeted the aromatase."

Dr Bulun successfully treated his patient with an aromatase inhibitor, supporting his idea that aromatase -- an enzyme which catalyzes the conversion of androgens to estrogens -- plays a key role in the pathophysiology of endometriosis.

Encouraged by his results, Dr Bulun went on to do a Phase II pilot study of the aromatase inhibitor letrozole in the treatment of endometriosis in pre-menopausal women. Letrozole is currently used in Canada to treat breast cancer in post-menopausal women. Dr Bulun and his colleagues found that the combination of letrozole and the progestin norethindrone acetate, was effective and well tolerated in pre-menopausal women with endometriosis, unresponsive to conventional treatment. The results of the study are published (appear or were published?) in the February issue of Fertility and Sterility.

Standard therapy for endometriosis is targeted at suppressing ovarian function. Among the most widely prescribed drugs for the disease are gonadotropin-releasing hormone (GnRH) analogs which act by reducing estrogen to post-menopausal levels. According to Dr Bulun and colleagues, GnRH analogs are not practical in the long-term due to associated bone loss and other side effects.

Dr Bulun's study included 10 pre-menopausal women with endometriosis who had not responded to previous medical and surgical treatments. The patients were given letrozole for six months and a progestin, norethindrone acetate, to counteract the effects of the drug on ovarian activity, and to minimize bone loss. The women also took calcium and vitamin D supplements.

The presence and the extent of the disease were diagnosed before and after treatment using laparoscopy -- a procedure that uses a viewing tube inserted in a small incision in the abdomen. (For more on laparoscopy, see Scoping out uterine fibroids on page 27). Patients kept a daily pain diary and were given monthly pelvic examinations. Bone density and hormone levels were also measured.

The endometriosis disappeared or was significantly reduced in all patients following letrozole treatment. Nine out of the 10 women experienced considerable pain relief during the study. No significant changes were seen in hormone levels and, despite fears of a potential loss of bone density, measurements of hip bone density even showed a notable improvement.

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

And Dr Bulun's patient from 1998? "She's still taking a reduced dose of the medication," he explained, "and she's doing well."