Estradiol is the predominant estrogen secreted by the ovary during the reproductive era.  The initial decline in ovarian function during perimenopause ultimately leads to an almost complete cessation of ovarian production of estrogens in the postmenopausal years.  Thus, postmenopausal women are deficient principally in estradiol. 
It is well recognized that in some women this deficiency rapidly results in the development of vasomotor symptoms and in atrophic changes within the genital tract.  Additionally, certain psychological symptoms--such as anxiety, forgetfulness and difficulty in concentrating (i.e. "menopausal syndrome")--increase in frequency during the climactic and early postmenopausal years.  Ovarian failure also has long-term consequences because postmenopausal women are at an increased risk of developing osteoporosis and certain fractures. 
Replacement of estrogen during the climactic and postmenopausal period not only relieves all the acute symptoms but also appears to protect against both the development of osteoporosis and the occurrence of the fractures. 
Currently, exogenous estrogen therapy is mainly prescribed by the oral route of administration: this therapy has certain disadvantages.  High doses of estrogen must be administered because of the rapid metabolism and inactivation of estrogens by the gut wall and liver (first pass effect).  It has been estimated that up to 30% of the administered dose is inactivated even before it reaches the systemic circulation. 
The potential advantage of delivering estradiol transdermal is that gut wall and hepatic metabolism may be avoided, thus not only allowing the use of lower total daily doses but also diminishing the risks of hepatic enzyme induction and its sequelae.  Transdermal delivery of estradiol can control menopausal symptoms effectively without inducting adverse metabolic changes. 
U.S. Pat.  No.  4,379,454 discloses a transdermal delivery system for estradiol.  This system is a permeable membrane-controlled reservoir system that uses ethanol as a skin penetration enhancer.  The estradiol is dissolved in the ethanol and both penetrate through the skin.  A permeable membrane is used for containing the diffusion rate.  An adhesive is applied on the permeable membrane.  The stability of this system is short and the delivery rate is not constant.  Moreover, the enhancer, ethanol, reacts with adhesive and causes lose of adhesion and, consequently, the system falls off the skin. 
U.S. Pat.  No.  4,390,520 discloses a transdermal delivery system for indomethacin.  This system is a drug-containing adhesive device.  The system comprises, in relevant part, indomethacin and a skin penetration enhancer, polyoxyethylene sorbitan mono-oleate ("polysorbate"), which are mixed into a adhesive copolymer, such as 2-ethylhexyl acrylate-vinyl acetate copolymer.  The indomethacin is dissolved directly into the copolymer. 
U.S. Pat.  No.  4,420,470 discloses a transdermal delivery system for drugs useful in suppressing or preventing attacks of angina pectoris; the drugs are isosorbide dinitrate and pentaerythritol tetranitrate.  This system is a drug-containing adhesive device.  The system comprises, in relevant part, the drug and skin penetration enhancer, such as polyethylene glycol, mixed with an adhesive copolymer, such as 2-ethylhexyl acrylate-vinyl acetate copolymer. 
U.S. Pat.  Nos.  4,291,014; 4,321,252; and 4,438,139, which are deemed cumulative of one another, each disclose a transdermal delivery system for estrogen-type drugs.  These systems are generally monolithic-type devices, i.e., an adhesive is interposed between the skin and matrix.  For example, U.S. Pat.  No.  4,438,139 discloses a matrix comprising a polar plasticizer, polyvinyl alcohol, polyvinyl pyrrolidone and estrogen.  The polar plasticizer is polyethylene glycol and is necessary to make the matrix flexible and to increase the reliability of diffusional release of the estrogen.  Additionally, a detergent (i.e. surfactant), such as sorbitan, and an absorption facilitator, may be added. 
U.S. Pat.  Nos.  4,058,122 and 4,077,407, which are deemed cumulative of one anther, each disclose a drug delivery system for estrogen.  These systems are generally reservoir-type devices.  For example, U.S. Pat.  No.  4,058,122 discloses a system comprising a wall, having a passageway, which surrounds an active agent.  In operation, the wall is permeable to external fluids which cross through the wall and which create an osmotic pressure within the wall.  The osmotic pressure forces the drug from behind the wall and through the passageway.  Materials which are added to the wall (lamina) to control flux through the wall include polyethylene glycol.  Dispersants, which are added to the wall to produce an integral composite, include polyoxyethylenated sorbitan oleate having a to 20 moles of ethylene oxide.