Objective: Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17β-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis.
Methods: This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters.
Results: In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years.
Conclusions: Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.
This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial with 500 osteopenic postmenopausal women that compared transdermal microdose E2 (0.014 mg/day) versus oral raloxifene (60 mg/day), administered for 2 years. Microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine (the primary efficacy endpoint). Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.
From 1Bayer Schering Pharma AG, Berlin, Germany; and 2Center for Clinical and Basic Research (CCBR), Byvej, Denmark.
Received July 28, 2008; revised and accepted September 22, 2008.
Funding/support: This study was supported by Bayer Schering Pharma AG, Berlin, Germany. Editorial support was provided by PAREXEL MMS.
Financial disclosure: Dr. Schaefers and Mr. Muysers are full-time employees of Bayer Schering Pharma AG. Dr. Alexandersen is a full-time employee of CCBR. Dr. Christiansen is the chief executive officer of Nordic Biosciences.
Address correspondence to: Matthias Schaefers, MD, Bayer Schering Pharma AG, Müllerstr. 178, 13353 Berlin, Germany. E-mail: firstname.lastname@example.org