Subcutaneous Depot Medroxyprogesterone Acetate versus Leuprolide Acetate in the Treatment of Endometriosis-Associated Pain

This study compared the effectiveness and safety of a new subcutaneous formulation of depot medroxyprogesterone acetate delivering 104 mg per 0.65 mL (DMPA-SC 104) every 3 months with those of leuprolide-a widely used and effective treatment for pain from endometriosis-in a dose of 3.75 mg per month (or 11.25 mg every 3 months). Bone mineral density (BMD) was estimated after 6 months of treatment and again at a 12-month follow-up assessment. Clinical end points included dysmenorrhea, dyspareunia, pelvic pain and tenderness, and induration. In addition, productivity was monitored at 6 and 18 months. Both treatments began in the first 5 days of a normal menstrual cycle. Participants were 299 women with laparoscopically diagnosed endometriosis; 153 were randomized to receive DMPA-SC 104, and 146 leuprolide. Between two thirds and three fourths of patients in both groups completed 12 months of follow up. The 2 treatment groups were initially similar in nearly all respects. All signs and symptoms of endometriosis were lessened as effectively by treatment with DMPA-SC 104 as with leuprolide. More than three fourths of patients in each treatment group maintained improvement at 12 months. Patients reported a higher quality of life with either treatment, and those in both treatment groups were satisfied with their results. Productivity also improved significantly in both groups. Patients taking leuprolide had significant reductions from baseline BMD in the total hip and lumbar spine regions after 6 months of treatment. A similar change occurred, in the spine only, in patients given DMPA-SC 104. At 12 months, BMD values were normal at both sites in the latter group, whereas women treated with leuprolide continued to have declining values at both sites. Hot flushes were less frequent in the DMPA-SC 104 group as was amenorrhea. Serious adverse events occurred in 4% of the DMPA-SC 104 group and 2% of patients given leuprolide. The most common side effect during follow-up was breast pain, which was slightly more frequent in the DMPA-SC 104 group. There were no clinically important changes in hematologic values, biochemical assays, or urinalysis. Although further long-term trials will be needed, the present findings suggest that DMPA-SC 104 may be suitable as a first-line treatment for women having pain caused by endometriosis. (Several investigators, including my colleagues and I.