A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss

Objective: To determine the effects of four doses of a 7-day transdermal 17 beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women. Methods: This was a multicenter, double-masked, randomized, placebo-control led study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, a nd 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy w as evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, p roximal femur, and total hip measured with dual-energy x-ray absorptiometry . serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentr ations were measured. Results: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day result ed in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density o f the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increa ses were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery syst em, effects of estrogen, and menopausal symptoms. Conclusion: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day ef fectively prevented bone loss in postmenopausal women. (C) 1999 by The Amer ican College of Obstetricians and Gynecologists.