Abstract: The present invention is directed to a transdermal delivery system for an active substance. The active substance is estrogen or its derivatives and preferably is 17-beta-estradiol. The system comprises an impermeable backing layer and a matrix affixed thereto. The matrix comprises, on a weight percentage basis, from about 60 to about 95% of an adhesive polymer, from about 5 to about 20% of a solvent, from about 0.2 to about 4% of a skin penetration enhancer, and from about 0.5 to about 5% of the active substance. The system is free of any discrete permeable, polymeric, diffusion-controlling membrane.