Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.
OBJECTIVE
Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-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.
Schaefers
Matthias
M
Bayer Schering Pharma AG, Berlin, Germany. matthias.schaefers@bayerhealthcare.com
Muysers
Christoph
C
Alexandersen
Peter
P
Christiansen
Claus
C
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*
D050071:Bone Density Conservation Agents; D004967:Estrogens; D020849:Raloxifene Hydrochloride; D004958:Estradiol