Three-year follow-up of the use of transdermal 17β-estradiol matrix patches for the prevention of bone loss in early postmenopausal women

OBJECTIVE: A total of 325 of 569 postmenopausal women who were initially recruited into two 2-year, double-blind, placebo-controlled, dose-ranging studies of a matrix transdermal formulation of 17 beta -estradiol (Menorest) participated in open-label extensions for a third year. STUDY DESIGN: Those patients originally randomly assigned to receive 17 beta -estradiol continued active treatment with dosages of 25, 50, 75, or 100 mug/d, whereas those originally randomly assigned to receive a placebo patch were switched to an active patch of identical size that delivered 17 beta -estradiol at 25, 50, 75, OF 100 mug/d. Follow-up was conducted, and bone density and other parameters were compared. RESULTS: Overall, gains in bone mass were maintained in patients who received 3 years of active treatment. In patients originally randomly assigned to receive placebo, initial losses in bone mass during the first 2 years were reversed and replaced with marked increases after the switch to active treatment. Ail patients who had initially received placebo showed significant, dose-related, clinically relevant increases (2.77% +/- 0.99%; P = .0048; to 7.36% +/- 0.74%; P = .0001) in lumbar spine bone mineral density relative to the end of the second year of the original study; smaller final-year increases were noted among the patients who had been actively treated for all 3 years. Similar trends were reported for femoral, trochanter, and total hip bone mineral densities. Mean total body bone mineral density either increased or remained unchanged in all dosage groups. These results were accompanied by parallel changes in levels of serum and urinary markers of bone turnover, with all markers approaching or returning to premenopausal levels by month 36. The high tolerability of this formulation during years 1 and 2 was maintained during year 3; 5.5% of patients withdrew from treatment because of adverse events in the final year. CONCLUSION: The Menorest formulation of transdermal 17 beta -estradiol maintained bone mineral density gains in postmenopausal women and was well tolerated through a 3-year treatment period. It was also effective in reversing the initial bone loss associated with late commencement of therapy.