Objectives: (A) Major 1) To compare the effectiveness of norethindrone acetate (NA) with agonist (Lupron- Depot-3 LD) in relieving pain from endometriosis, 2) To compare the effects of NA and Lupron treatment on bone density; (B) Minor: 1) To compare the effects of NA and Lupron treatment on lipid profile, 2) To determine the effects of treatment on quality of life, 3) To determine whether NA has fewer adverse effects than GnRH agonist (LD). 112 women with symptomatic endometriosis diagnosed surgically, will be treated double blind fashion with NA or Lupron-Depot-3 for 24 weeks in Phase I study. After 24 weeks both groups will be treated only with NA until 52 week in Phase II study (Phase III). Both groups will be followed for an additional 52 weeks to assess any return of clinical symptoms and to determine whether laboratory tests of drug related changes return to pretreatment levels. Treatment regimens are as follow: For the first 24 weeks, women in the NA group will be treated with 5 mg NA daily and a placebo injection every 12 weeks, In case of bleeding, the NA dose will be increased 5 mg every 2 weeks (max 15 mg) until bleeding stops, and then decreased by 2.5 mg every 4 weeks to a final dose of 7.5 mg which will be maintained for the remainder of the 24 weeks. For the first 24 weeks, women in the GnRH groups will receive Lupron-Depot-3 injections every 12 weeks plus placebo pills daily - bleeding will be treated as NA group. After 24 weeks, in the second phase of the study all women will be on identical regimens of 5 mg NA pills daily and no injections. On the first treatment day, subjects will have the following tests/assessments: menstrual and daily diary, questionnaires and physical examination each visit. All tests, except bone density will be repeated at 12, 24, 52 of treatment and then again 3 and 12 months during follow-up period. DEXA will be performed once every 6 months during treatment and 12 month follow-up period. The objectives will be compared between the group at 12, 24 and 52 weeks of treatment and at 6 month intervals during the follow-up period.
