A dose-ranging trial of a matrix transdermal 17 beta-estradiol for the prevention of bone loss in early postmenopausal women

This international, randomized, double-blind, placebo-controlled, parallel group, dose-ranging trial was designed to determine the efficacy of 2 years of therapy with a mew matrix transdermal 17 beta-estradiol (Menorest) in p reventing bone loss in early postmenopausal women, and to identify an appro priate dose. Two hundred ninety-two ambulatory women with natural or surgic al menopause for 1-6 years were randomized to receive patches delivering 17 beta-estradiol 50, 75, or 100 mu g/day twice weekly for 25 days per 28 day cycle (with dydrogesterone 10 mg twice daily from days 11 to 24) or placeb o, for 24 months. The primary outcome measure was the percentage change fro m baseline in lumbar spine bone mineral density (BMD) at 2 years. Secondary endpoints were percentage changes from baseline in three sites of proximal femur BMD and total body BMD, and in biochemical bone turnover markers. At 2 years, the difference from placebo in percentage change from baseline of L1-4 spine BMD was 6.2%, 7.6%, and 7.8% in the 50, 75, and 100 mu g/day gr oups, respectively. Lumbar spine bone increased in 65.5%, 76.8%, and 81.0% of patients in the respective active treatment groups, compared with 4.9% o n placebo. BMD increased significantly relative to placebo in the femoral n eck, trochanter, total hip, and total body. Serum osteocalcin, bone alkalin e phosphatase and urinary type I collagen C-telopeptide decreased significa ntly and dose dependently in 17 beta-estradiol patients vs. placebo. For ex ample, at 2 years, the difference between placebo and the 50 mu g/day group , expressed in percentage change from baseline, was 3.25% at the femoral ne ck, 3.92% at the trochanter, 3.52% for total hip, and 2.40% for the total b ody. Breast pain and skin reactions were more common in the actively treate d groups, but tolerability was generally good. Therefore, after 2 years, 17 beta-estradiol was well-tolerated and highly effective at doses of between 50 and 100 mu g/day in preventing bone loss and reducing bone turnover in early postmenopausal women. The dose of 50 mu g/day, the lowest dose tested , is a suitable dose. There was little clinical benefit of increasing the d osage from 75 to 100 mu g/day. (C) 1999 by :Elsevier Science Inc. All right s reserved.