Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group.
A total of 277 early postmenopausal women were enrolled in this placebo-controlled 2-year study to examine the efficacy of a matrix transdermal 17beta-estradiol system, at three different dosages (25, 50 and 75 mg/day) combined with sequential oral dydrogesterone 20 mg/day, in preventing bone loss. At 2 years, the difference from placebo in percentage change from baseline of L1-4 lumbar spine bone mineral density (BMD) (assessed by dual-energy X-ray absorptiometry) was 4.7% +/- 0.7% with estradiol 25 mg/day, 7.3% +/- 0.7% with estradiol 50 mg/day and 8.7% +/- 0.7% with estradiol 75 mg/day (all values mean +/- SEM). There were also significant increases in femoral neck, trochanter and total hip BMD with all doses of estradiol compared with placebo. Additionally, most patients had a significant gain (increase greater than 2.08%) in lumbar spine bone mass compared with placebo. Patients who received estradiol also experienced clinically significant and dose-related decreases in total serum osteocalcin, serum bone alkaline phosphatase and urinary C-telopeptide, with all three markers of bone turnover returning to premenopausal levels. Estradiol was well tolerated during the 2-year treatment period. Transdermal estradiol is effective and well tolerated at dosages between 25-75 mg/day in the prevention of bone loss in postmenopausal women; 25 mg/day offers an effective option for those women who cannot tolerate higher doses.
Cooper
C
C
Southampton General Hospital, Southampton, UK.
Stakkestad
J A
JA
Radowicki
S
S
Hardy
P
P
Pilate
C
C
Dain
M P
MP
Delmas
P D
PD
D000279:Administration, Cutaneous; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology / Q000517:prevention & control*; D010455:Peptides / Q000652:urine
D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D004958:Estradiol; D003094:Collagen; D000469:Alkaline Phosphatase