OBJECTIVE: To determine the lowest effective dose of an estradiol (E ) matrix-type transdermal delivery system (EMTDS; Alora) for preventing bone loss in postmenopausal women. DESIGN: This double-blind, double-dummy, randomized, placebo-controlled, multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier. Participants were randomly assigned to one of three doses of the EMTDS (0.025, 0.05, or 0.075 mg/day) or placebo administered twice weekly. Lumbar bone mineral density (LBMD) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment. Safety was assessed at regularly scheduled visits. RESULTS: EMTDS provided statistically significant and clinically meaningful changes in LBMD relative to placebo. At 2 years, LBMD declined from baseline by 0.59% in the placebo group, but it increased from baseline by 1.65% ( = 0.0065), 4.08% ( = 0.0001), and 4.82% ( = 0.0001) in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. The corresponding responder rates (defined as no change or increase in LBMD at endpoint) were 39.7% for placebo, 59.6%, 79.3%, and 83.9% in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. Mean serum E concentrations were proportional to the dose of the E transdermal system and did not accumulate over the course of the study. Adverse events were generally comparable across treatment groups, with the majority being mild or moderate in severity and unrelated to study medication. Mammogram findings and other safety assessments were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E treatment. CONCLUSIONS: The EMTDS (Alora) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women, with the benefit of treatment evident by 1 year. The lowest effective dose is 0.025 mg/day.
RCT Entities:
OBJECTIVE: To determine the lowest effective dose of an estradiol (E ) matrix-type transdermal delivery system (EMTDS; Alora) for preventing bone loss in postmenopausal women. DESIGN: This double-blind, double-dummy, randomized, placebo-controlled, multicenter study enrolled 355 nonosteoporotic postmenopausal women who had been hysterectomized with or without oophorectomy at least 12 months earlier. Participants were randomly assigned to one of three doses of the EMTDS (0.025, 0.05, or 0.075 mg/day) or placebo administered twice weekly. Lumbar bone mineral density (LBMD) was measured by dual-energy x-ray absorptiometry at screening and after 1 and 2 years of treatment. Safety was assessed at regularly scheduled visits. RESULTS: EMTDS provided statistically significant and clinically meaningful changes in LBMD relative to placebo. At 2 years, LBMD declined from baseline by 0.59% in the placebo group, but it increased from baseline by 1.65% ( = 0.0065), 4.08% ( = 0.0001), and 4.82% ( = 0.0001) in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. The corresponding responder rates (defined as no change or increase in LBMD at endpoint) were 39.7% for placebo, 59.6%, 79.3%, and 83.9% in the EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. Mean serum E concentrations were proportional to the dose of the E transdermal system and did not accumulate over the course of the study. Adverse events were generally comparable across treatment groups, with the majority being mild or moderate in severity and unrelated to study medication. Mammogram findings and other safety assessments were also comparable across groups and did not reveal any safety concerns with 2-y transdermal E treatment. CONCLUSIONS: The EMTDS (Alora) administered twice weekly improves lumbar bone mineral density in healthy postmenopausal women, with the benefit of treatment evident by 1 year. The lowest effective dose is 0.025 mg/day.