Estradiol Transdermal System

Estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mg of estradiol daily, depending on the phase of the menstrual cycle. After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism and estrogen replacement therapy acts to reduce the elevated levels of these hormones seen in postmenopausal women.

In two 12-week, double-blind, placebo-controlled studies, a total of 442 postmenopausal women received TRADENAME (either 0.05, 0.075, or 0.1 mg per day) and 151 received placebo patches. On average, these patients had approximately 12 to 13 hot flushes per day upon study entry. After 4 weeks of treatment, all 3 TRADENAME groups showed a significantly greater reduction in the mean daily number and severity of hot flushes vs. placebo.

Occasional elevated blood pressure. Hypercoagulability.

The TRADENAME transdermal system releases 17b-estradiol continuously upon application to intact skin. Estradiol USP (17b-estradiol) is a white, crystalline powder, chemically described as estra-1,3,5(10)-triene-3,17b-diol. It has an empirical formula of C18H24O2 and molecular weight of 272.37.1. TRADENAME has three layers: Proceeding from the visible surface toward the surface attached to the skin, these layers are (1) the backing, a layer composed of a translucent coextruded polymeric barrier film that provides structural support and protects the middle layer from the environment, (2) the opaque middle adhesive/drug matrix layer that contains 17b-estradiol, acrylic adhesive, polyvinylpyrrolidone, and aluminum acetylacetonate, and (3) the release liner, a metallic film coated with silicone that protects the adhesive layer during storage and must be removed and discarded just before the system is applied. Release of estradiol from the system is primarily controlled by the adhesive, which ensures adhesion of the middle layer to the backing and of the product to the skin.