Abstract
Circulating plasma levels of 17 beta-estradiol after the administration of fixed dosages of 17 beta-estradiol show great variability depending upon product formulation, route of administration, and interindividual variation in absorption and metabolism. Two new 17 beta-estradiol transdermal delivery systems, Systen(R)50 (also called Evorel(R)) and Menorest(R)50 have recently been approved in Europe for the treatment of climacteric symptoms. Both transdermal systems deliver 17 beta-estradiol at a rate of 50 mu g/day. The present study was undertaken to compare the plasma profiles of 17 beta-estradiol delivered by these 2 products in 30 healthy postmenopausal women according to a randomised,monocentric, single-blind, crossover protocol. Two 4-day patch application periods were separated by a 7-day washout period. Plasma 17 beta-estradiol concentrations were determined 24 hours and 30 minutes before and then 0, 2, 4, 8, 12, 24, 48, 60, 72, 84 and 96 hours after the first patch administration. 17 beta-Estradiol measurements were performed using a specific direct radioimmunoassay developed at the French Fondation de Recherche en Hormonologie laboratory. Bioequivalence was assessed by analysis of variance. The results demonstrated that the 2 products were similar in terms of maximum plasma concentration; however, mean concentration, concentration at 96 hours and area under the concentration-time curve were significantly (p < 0.05) greater with Menorest(R)50. Furthermore, 17 beta-estradiol concentrations decreased more rapidly with Systen(R)50 than with Menorest(R)50. These differences in the plasma profiles of 2 transdermal systems both delivering 50 mu g/day of 17 beta-estradiol may have important clinical consequences both in terms of tolerance and effectiveness.