Estrogen beta receptor agonists to prevent or reduce the severity of cardiovascular disease

Abstract

A method for preventing or treating vascular hyperreactivity in which a chemical compound that is an estrogen beta receptor agonist is administered to a subject suffering from or at risk of vascular hyperreactivity. Preferably, the administration is topically to the skin.

1 . A method for reducing the incidence or severity of vascular hyperreactivity in a patient in need thereof comprising administering to the patient an effective amount of a selective estrogen beta receptor agonist that has a higher relative potency for estrogen receptor beta compared to estrogen receptor alpha than that of genistein. 
   
   
       2 . The method of  claim 1  wherein the vascular hyperreactivity of the patient is manifested by coronary arterial vasospasm. 
   
   
       3 . The method of  claim 1  wherein the vascular hyperreactivity of the patient is manifested by hyperreactivity of peripheral arteries. 
   
   
       4 . The method of  claim 1  wherein the estrogen beta receptor agonist is co-administered with a hormone replacement therapy. 
   
   
       5 . The method of  claim 4  wherein the hormone replacement therapy is selected from the group consisting of estrogen, androgen, and progestin therapy. 
   
   
       6 . The method of  claim 1  wherein the estrogen beta receptor agonist is administered to the patient by topical application to skin. 
   
   
       7 . The method of  claim 6  wherein the estrogen beta receptor agonist is in a topical preparation selected from the group consisting of a liquid, cream, gel, lotion, ointment, and transdermal patch. 
   
   
       8 . The method of  claim 1  wherein the estrogen beta receptor agonist is administered to the patient by other than topical administration to skin. 
   
   
       9 . The method of  claim 8  wherein administration is by oral, rectal, vaginal, topical, sublingual, nasal, intradermal, inhalation, or sustained implant administration routes. 
   
   
       10 . A kit for administering an estrogen beta receptor agonist compound to a patient suffering from or at risk of vascular hyperreactivity comprising a container, a topical preparation containing an estrogen beta receptor agonist in the container, and instructions for dispensing an amount of the preparation which provides an amount of the estrogen beta receptor agonist that is effective to prevent or reduce the severity of vascular hyperreactivity. 
   
   
       11 . The kit of  claim 10  wherein the estrogen beta receptor agonist is 5α-androstane-3β,17β-diol. 
   
   
       12 . The kit of  claim 10  wherein the estrogen beta receptor agonist is a derivative of 5α-androstane-3β,17β-diol that has estrogen beta receptor agonist activity. 
   
   
       13 . The kit of  claim 12  wherein the derivative of 5α-androstane-3β,17β-diol is selected from the group consisting of 5α-androstan-3β,17β-diol-3 hemisuccinate, 5α-androstan-3β,17β-diol-17-sulphate sodium salt, 5α-androstan-3β,17β-diol-3-acetate, 5α-androstan-3β,17β-diol-17-acetate, 5α-androstan-3β,17β-diol-diacetate, 5α-androstan-3β,17β-diol-dibenzoate, 5α-androstan-3β,17β-diol-dihemisuccinate, 5α-androstan-3β,17β-diol-diproprionate, and 5α-androstan-3β,17β-diol-17-hexahydrobenzoate. 
   
   
       14 . The kit of  claim 10  wherein the estrogen beta receptor agonist is epiestriol. 
   
   
       15 . The kit of  claim 10  wherein the estrogen beta receptor agonist is genistein or diarylpropionitrile. 
   
   
       16 . The kit of  claim 10  wherein the topical preparation is selected from the group consisting of a liquid, cream, gel, lotion, ointment, and transdermal patch.