Objective: To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA- SC 104) with that of leuprolide acetate in treatment of endometriosis. Design: Phase 3, multicenter, randomized, evaluator- blinded, comparator- controlled trial. Setting: Clinical trial sites in Canada and United States. Patient(s): Two hundred seventy- four women with surgically diagnosed endometriosis. Intervention(s): Intramuscular injections of DMPA- SC (104 mg) or leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months of posttreatment follow- up. Main Outcome Measure(s): Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density (BMD), hypoestrogenic symptoms, bleeding, and weight. Result(s): The depot medroxyprogesterone acetate given SC was statistically equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (month 6) and in reducing all five symptoms after 12 months’ follow- up (month 18). Patients in the DMPA- SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6, with scores returning to baseline at 12 months’ follow- up. No statistically significant differences in median weight changes were observed between groups. Compared with leuprolide, DMPASC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding. Conclusion(s): Efficacy of DMPASC 104 was equivalent to that of leuprolide for reducing endometriosis- associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding. Objective: To compare the efficacy and safety of SC depot medroxyprogesterone acetate (DMPA-SC 104) with that of leuprolide acetate in treatment of endometriosis. Design: Phase 3, multicenter, randomized, evaluator- blinded, comparator- controlled trial. trial sites in Canada and United States. Patient (s): Two hundred seventy-four women with surgically diagnosed endometriosis. Intervention (s): Intramuscular injections of DMPA- SC (104 mg) or leuprolide acetate months for 6 months, with 12 months of posttreatment follow-up. Main Outcome Measure (s): Reduction in five endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, pelvic induration); change in bone mineral density Result (s): The depot medroxyprogesterone acetate given SC was expressed equivalent to leuprolide in reducing four of five endometriosis symptoms or signs at the end of treatment (m onth 6) and in reducing all five symptoms after 12 months’ follow-up (month 18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than did leuprolide patients at month 6, with scores returning to baseline at 12 months Compared with leuprolide, DMPASC 104 was associated with fewer hypoestrogenic symptoms but more irregular bleeding. Conclusion (s): Efficacy of DMPASC 104 was equivalent to that of leuprolide for reducing endometriosis-associated pain, with less impact on BMD and fewer hypoestrogenic side effects but more bleeding.