Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial.
This 2-year, double-masked, randomized, placebo-controlled trial was designed to evaluate the safety and efficacy in preventing bone loss in postmenopausal women of two doses of transdermal 17betaestradiol (estradiol) delivered by a matrix patch, compared with placebo. One hundred and sixty healthy, hysterectomized postmenopausal volunteers aged 40-60 years with serum estradiol levels < 20 pg/ml were started on treatment at four centers in The Netherlands. Every 6 months, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, non-dominant wrist and left hip, and markers of bone turnover were assessed in urine and serum. The treatment arms were: estradiol, 100 microg/day (E-100, n = 53), oestradiol, 50 microg/day (E-50, n = 54), placebo (P-100, placebo to E-100, n = 27 or P-50, placebo to E-50, n = 26). Treatment was continued for up to 2 years. After 24 months, BMD of the lumbar spine in the E-100 group differed by 7.7% [5.8-9.5%] (mean [95% confidence interval]) from the placebo group and showed a mean (s.e.m.) increase in BMD from baseline of 5.9% (0.69%). For the E-50 group the difference compared with placebo was 6.2% [4.4-8.0%] and the absolute increase was 4.5% (0.62%); in the placebo group, the absolute change was -2.3% (0.48%). In the total wrist, the changes were: E-100: difference compared with placebo 2.5% [1.5 3.6%], absolute increase 0.6% (0.3%); E-50: difference compared with placebo 2.9% [1.8-3.9%], absolute increase 0.7% (0.25%); and absolute change on placebo: -2.5% (0.35%). In the total hip, the changes were: E-100: difference compared with placebo 3.7% [2.2-5.2%], absolute increase 2.8% (0.5%); E-50: difference compared with placebo: 3.2% [1,8-4.7%], absolute change 2.4% (0.36%); and absolute change on placebo -1.4% (0.66%). Three markers of bone turnover--serum bone-specific alkaline phosphatase, serum osteocalcin and urinary CTX--fell significantly during the trial. Breast pain was reported by 8% of women on placebo, by 6% of women on E-50 and by 17% of women on E-100. Estradiol delivered by the E-50 matrix patch effectively reversed bone loss in hysterectomized postmenopausal women with few side-effects. The marginal additional gain in BMD with the higher dose may be offset by a more important side effect profile.
Arrenbrecht
S
S
The R.W. Johnson Pharmaceutical Research Institute, Switzerland. stefan.arrenbrecht@freesurf.ch
Boermans
A J M
AJ
D000279:Administration, Cutaneous; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014955:Wrist Joint / Q000503:physiopathology
D004958:Estradiol