New low dose depot medroxyprogesterone acetate subcutaneous injection is equivalent to leuprolide acetate for endometriosis-associated pain

Abstract

To compare the efficacy and safety of a new low dose subcutaneous formulation of depot medroxyprogesterone acetate (DMPA-SC) with leuprolide acetate (LA) for endometriosis-associated pain. This 18-month (6 month treatment; 12 month follow-up), randomized, evaluator-blind, multicenter, comparator-controlled trial was conducted in the United States and Canada. Premenopausal women (18–49 years) with laparoscopically diagnosed endometriosis, or with persistent, recurrent endometriosis-associated symptoms for at least 3 months, were included. Treatment consisted of DMPA-SC 104 mg every 3 months or LA 11.25 mg given intramuscularly every 3 months. Efficacy endpoints included response to treatment in 5 endometriosis-associated pain categories; safety endpoints included bone mineral density (BMD) changes, hot flushes, and adverse events. All 274 randomized subjects received at least 1 dose of study medication and constituted the intent-to-treat population (DMPA-SC, 136; LA, 138); 69.3% completed treatment. Treatment with DMPA-SC was statistically equivalent (P<.02) to LA for alleviating 4 of the 5 signs/symptoms of endometriosis (dysmenorrhea, dyspareunia, pelvic pain, and pelvic tenderness) at month 6. Statistically significant and clinically meaningful improvements in the composite score were observed at month 6 in each treatment group (mean change, -6.2[DMPA-SC]; -7.7[LA]). Twelve months after stopping treatment (month 18), DMPA-SC was statistically equivalent (P<.02) to LA in reducing all 5 endometriosis symptoms (dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and induration). Significant and clinically meaningful improvements were observed at month 18 in the composite score (mean change of -5.3[DMPA-SC] vs. -5.1[LA]). BMD decline with DMPA-SC was significantly less compared to LA at month 6 and 18 (Table 1). The median average daily number of hot flushes (recorded in patient diaries) and the maximum severity of hot flushes were significantly lower in the DMPA-SC group than in the leuprolide group beginning at month 1 and continuing throughout the 6-month treatment period. The percentage of subjects with at least one treatment-related adverse event was similar between DMPA-SC (47.7%) and LA (45.2%) groups. DMPA-SC 104 mg every 3 months is equally effective as LA 11.25 mg IM every 3 months for endometriosis-associated pain. BMD decline with DMPA-SC was significantly less than LA after 6 months treatment and returned to baseline 12 months post-discontinuation, while LA did not.