Objective: To determine the role of an aromatase inhibitor, letrozole, in the treatment of reproductive-age women with endometriosis and associated chronic pelvic pain.

Design: Phase 2, open-label, nonrandomized proof-of-concept study.

Setting: Outpatient tertiary-care center.

Patient(s): Ten patients with endometriosis, all previously treated both medically and surgically, with unsatisfactory results.

Intervention(s): Endometriosis was diagnosed by biopsy and scored from an initial diagnostic laparoscopy performed within 1 month before treatment was begun. Oral administration of letrozole (2.5 mg), the progestin norethindrone acetate (2.5 mg), calcium citrate (1,250 mg), and vitamin D (800 IU) was done daily for 6 months. Within 1-2 months after completion of the treatment, a second-look laparoscopy was performed to score and biopsy endometriosis.

Main outcome measure(s): Changes in American Society for Reproductive Medicine (ASRM) scores for endometriosis, pelvic pain assessed by visual analog scale, serum hormone levels (FSH, LH, E(2), and estrone [E(1)]), and bone density (DEXA scan).

Result(s): No histologically demonstrable endometriosis was present in any patient during the second-look laparoscopy. ASRM and pelvic pain scores decreased significantly in response to treatment. Overall, no significant change in bone density was detected. Gonadotropin levels were not significantly altered by treatment, and although circulating E(2) and E(1) levels were reduced, the decrease was not statistically significant.

Conclusion(s): The combination of letrozole and norethindrone acetate achieved marked reduction of laparoscopically visible and histologically confirmed endometriosis in all 10 patients and significant pain relief in nine out of 10 patients who had not responded previously to currently available treatments. On this basis, letrozole should be a candidate for the medical management of endometriosis.