Matrix delivery transdermal 17beta-estradiol for the prevention of bone loss in postmenopausal women. The International Study Group

Osteoporos Int. 1999;9(4):358-66. doi: 10.1007/s001980050159.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Alkaline Phosphatase / blood
  • Analysis of Variance
  • Biomarkers / blood
  • Biomarkers / urine
  • Bone Density / drug effects
  • Bone Remodeling / drug effects
  • Collagen / urine
  • Collagen Type I
  • Double-Blind Method
  • Drug Administration Schedule
  • Estradiol / administration & dosage*
  • Estradiol / therapeutic use
  • Female
  • Humans
  • Lumbar Vertebrae
  • Middle Aged
  • Osteocalcin / blood
  • Osteoporosis, Postmenopausal / physiopathology
  • Osteoporosis, Postmenopausal / prevention & control*
  • Peptides / urine


  • Biomarkers
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Estradiol
  • Collagen
  • Alkaline Phosphatase