Steroid treatment for hot flashes

Abstract

Embodiments of the invention relate to methods for treating individuals suffering from hot flashes by vomeronasally administering a therapeutically effective dosage of a steroid agent. The hot flashes may be a result of postmenopause or castration suffered by the individual. In many embodiments, the method for treating individuals suffering with hot flashes is provided by administering a steroid agent containing an estrene compound, such as 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one, to the individual. In other embodiments, pharmaceutical compositions containing the steroid agent may be used to treat individuals suffering with hot flashes. Embodiments include methods for treating male castrates, as well as postmenopausal women and men, suffering from hot flashes by vomeronasally administering a steroid agent containing 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one to levitate the hot flashes.

1 . A method for treating a male castrate suffering from hot flashes, comprising vomeronasally administering a therapeutically effective dosage of a steroid agent comprising 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one to the male castrate. 
   
   
       2 . The method of  claim 1 , wherein the steroid agent is administered to the male castrate at an onset of a hot flash. 
   
   
       3 . The method of  claim 1 , wherein the steroid agent is administered to the male castrate on a daily schedule. 
   
   
       4 . The method of  claim 3 , wherein the steroid agent is administered from 2 to 8 times per day during the daily schedule. 
   
   
       5 . The method of  claim 4 , wherein the steroid agent is administered from 3 to 5 times per day during the daily schedule. 
   
   
       6 . The method of  claim 1 , wherein the therapeutically effective dosage of the steroid agent comprises 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one at a concentration within a range from about 100 ng to about 4,000 ng. 
   
   
       7 . The method of  claim 6 , wherein the concentration is within a range from about 400 ng to about 1,600 ng. 
   
   
       8 . The method of  claim 1 , wherein the steroid agent is topically administered to a vomeronasal organ of the male castrate. 
   
   
       9 . The method of  claim 8 , wherein the steroid agent is further coated with a time-release agent. 
   
   
       10 . The method of  claim 8 , wherein the vomeronasal organ is exposed to a cream, a gel, or an ointment comprising the steroid agent during the administration. 
   
   
       11 . The method of  claim 8 , wherein the vomeronasal organ is exposed to a nasal spray or a nasal powder spray comprising the steroid agent during the administration. 
   
   
       12 . The method of  claim 11 , wherein the nasal spray comprises the steroid agent and water. 
   
   
       13 . The method of  claim 12 , wherein the nasal spray further comprises at least one excipient. 
   
   
       14 . The method of  claim 13 , wherein the at least one excipient comprises propylene glycol, ethanol, or mixtures thereof. 
   
   
       15 . The method of  claim 11 , wherein the nasal powder spray comprises aerosol particulate of the steroid agent. 
   
   
       16 . The method of  claim 1 , wherein the male castrate has actual castration. 
   
   
       17 . The method of  claim 16 , wherein the male castrate has had at least one testicle surgically removed during the actual castration. 
   
   
       18 . The method of  claim 17 , wherein the male castrate has had both testicles surgically removed during the actual castration. 
   
   
       19 . The method of  claim 16 , wherein the male castrate has been administered a cancer treatment. 
   
   
       20 . The method of  claim 19 , wherein the cancer treatment was for testicular cancer, prostate cancer, or metastatic prostate cancer. 
   
   
       21 . The method of  claim 18 , wherein the male castrate is a transsexual. 
   
   
       22 . The method of  claim 1 , wherein the male castrate has chemical castration. 
   
   
       23 . The method of  claim 22 , wherein the male castrate has been administered at least one antiandrogen compound during a treatment. 
   
   
       24 . The method of  claim 23 , wherein the at least one antiandrogen compound is selected from the group consisting of bicalutamide, cyproterone, flutamide, nilutamide, derivatives thereof, salts thereof, and combinations thereof. 
   
   
       25 . The method of  claim 22 , wherein the male castrate has been administered at least one luteinizing hormone releasing hormone antagonist compound during a treatment. 
   
   
       26 . The method of  claim 25 , wherein the at least one luteinizing hormone releasing hormone antagonist compound is selected from the group consisting of buserelin, goserelin, leuprolide, triptorelin, derivatives thereof, salts thereof, and combinations thereof. 
   
   
       27 . The method of  claim 22 , wherein the male castrate has been administered a cancer treatment. 
   
   
       28 . The method of  claim 27 , wherein the cancer treatment was for prostate cancer or metastatic prostate cancer. 
   
   
       29 . The method of  claim 27 , wherein the male castrate is temporally castrated during or subsequent the cancer treatment. 
   
   
       30 . The method of  claim 27 , wherein the male castrate is permanently castrated during or subsequent the cancer treatment. 
   
   
       31 . The method of  claim 22 , wherein the male castrate has been administered the steroid agent during a treatment to reduce sexual capability. 
   
   
       32 . The method of  claim 22 , wherein the male castrate is a transsexual. 
   
   
       33 . A method for treating a male castrate suffering from hot flashes, comprising administering a therapeutically effectively amount of a steroid agent within a nasal passage of the male castrate, wherein the steroid agent binds specifically to receptors on the surface of nasal neuroepithelial cells of the male castrate to alleviate the hot flashes, and the nasal neuroepithelial cells are part of tissue other than olfactory epithelia. 
   
   
       34 . The method of  claim 33 , wherein the steroid agent is an estrene compound having the chemical formula of: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  is selected from the group consisting of one hydrogen atom, two hydrogen atoms, methyl, methylene, one halogen atom, and two halogen atoms; 
 R 2  is absent or is selected from the group consisting of hydrogen and methyl; 
 R 3  is selected from the group consisting of oxo, hydroxy, lower alkoxy, lower acyloxy, benzoyl, cypionyl, glucuronide, and sulfonyl; 
 R 4  is selected from the group consisting of hydrogen, hydroxy, lower alkoxy, lower acyloxy, and halo; 
 R 5  is absent or is selected from the group consisting of hydrogen, hydroxy, lower alkoxy, and lower acyloxy; 
 R 6  is hydrogen or halogen; 
 “a” represents optional aromatic unsaturation of ring A of the steroid, or “b”, “c”, and “d” are each optional double bonds; 
 “e”, “f”, “g”, “h”, “i”, and “j” are each optional double bonds; and 
 “e” may also form an epoxy ring with C 16  and C 17 . 
 
   
   
       35 . The method of  claim 34 , wherein “a” is present and “g”, “h”, or “i” are optional double bonds. 
   
   
       36 . The method of  claim 35 , wherein “h” and “i” are both double bonds. 
   
   
       37 . The method of  claim 34 , wherein “b” is a double bond. 
   
   
       38 . The method of  claim 34 , wherein “j” is a double bond. 
   
   
       39 . The method of  claim 34 , wherein “c” is a double bond. 
   
   
       40 . The method of  claim 34 , wherein “c” and “d” are double bonds. 
   
   
       41 . The method of  claim 34 , wherein R 2  is methyl and “e” is a double bond. 
   
   
       42 . The method of  claim 34 , wherein the estrene compound is selected from the group consisting of estra-4,16-dien-3-one; estra-1,3,5(10),16-tetraene-3-ol; estra-4,16-dien-3α-ol; estra-4,9(10),16-triene-3-one; estra-1,3,5(10),16-tetraen-3-ol-6-one; 3-methoxyl-estra-2,5(10),16-triene; estra-5(10),16-dien-3α-ol; and estra-1,3,5(10),16-tetraen-3,6α-diol. 
   
   
       43 . The method of  claim 34 , wherein R 5  is methyl. 
   
   
       44 . The method of  claim 43 , wherein the estrene compound is selected from the group consisting of estra-1,3,5(10)-trien-3-ol; estra-1,3,5(10),6-tetraen-3-ol; and estra-1,3,5(10),7-tetraen 3-ol. 
   
   
       45 . The method of  claim 34 , wherein R 1  is methylene. 
   
   
       46 . The method of  claim 45 , wherein the estrene compound is 17-methylene-estra-1,3,5(10),6,8(9)hexaen-3-ol. 
   
   
       47 . The method of  claim 34 , wherein R 1  is methylene or one hydrogen atom and R 2  is methyl. 
   
   
       48 . The method of  claim 34 , wherein “f” is a double bond and R 2  is methyl. 
   
   
       49 . The method of  claim 48 , wherein the estrene compound is selected from the group consisting of 1,3,5(10),16-estratetraen-3-ol-methyl ether; 1,3,5(10),16-estratetraen-3-ol; 1,3,5(10),16-estratetraen-3-yl acetate; and 1,3,5(10),16-estratetraen-3-yl propionate. 
   
   
       50 . The method of  claim 48 , wherein the estrene compound is 1,3,5(10),16-estratetraen-3-ol. 
   
   
       51 . The method of  claim 34 , wherein the estrene compound is estra-4,16-dien-10β-ol-3-one. 
   
   
       52 . The method of  claim 34 , wherein “e” forms an epoxy ring with C 16  and C 17 . 
   
   
       53 . The method of  claim 52 , wherein the estrene compound is 16α,17α-epoxy-estra-1,3,5(10)-trien-3-ol. 
   
   
       54 . The method of  claim 52 , wherein the estrene compound is 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one. 
   
   
       55 . A method for treating a male individual having a testosterone level of about 50 ng/dL or less and suffering from hot flashes, comprising vomeronasally administering a therapeutically effective dosage of a steroid agent comprising 16α, 17α-epoxy-10β-hydroxyestr-4-en-3-one to the male individual. 
   
   
       56 . The method of  claim 55 , wherein the testosterone level is about 20 ng/dL or less. 
   
   
       57 . The method of  claim 55 , wherein the steroid agent is administered to the male individual at an onset of a hot flash. 
   
   
       58 . The method of  claim 55 , wherein the steroid agent is administered to the male individual on a daily schedule. 
   
   
       59 . The method of  claim 58 , wherein the steroid agent is administered from 2 to 8 times per day during the daily schedule. 
   
   
       60 . The method of  claim 59 , wherein the steroid agent is administered from 3 to 5 times per day during the daily schedule. 
   
   
       61 . The method of  claim 55 , wherein the therapeutically effective dosage of the steroid agent comprises 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one at a concentration within a range from about 100 ng to about 4,000 ng. 
   
   
       62 . The method of  claim 61 , wherein the concentration is within a range from about 400 ng to about 1,600 ng. 
   
   
       63 . The method of  claim 55 , wherein the male individual is a male castrate having actual castration. 
   
   
       64 . The method of  claim 63 , wherein the male castrate has had both testicles surgically removed during the actual castration. 
   
   
       65 . The method of  claim 63 , wherein the male castrate has been administered a cancer treatment. 
   
   
       66 . The method of  claim 65 , wherein the cancer treatment was for testicular cancer, prostate cancer, or metastatic prostate cancer. 
   
   
       67 . The method of  claim 55 , wherein the male individual is a male castrate having chemical castration. 
   
   
       68 . The method of  claim 67 , wherein the male castrate has been administered at least one antiandrogen compound during a treatment. 
   
   
       69 . The method of  claim 68 , wherein the antiandrogen compound is selected from the group consisting of bicalutamide, cyproterone, flutamide, nilutamide, derivatives thereof, salts thereof, and combinations thereof. 
   
   
       70 . The method of  claim 67 , wherein the male castrate has been administered at least one luteinizing hormone releasing hormone antagonist compound during a treatment. 
   
   
       71 . The method of  claim 70 , wherein the luteinizing hormone releasing hormone antagonist compound is selected from the group consisting of buserelin, goserelin, leuprolide, triptorelin, derivatives thereof, salts thereof, and combinations thereof. 
   
   
       72 . The method of  claim 67 , wherein the male castrate has been administered a cancer treatment. 
   
   
       73 . The method of  claim 72 , wherein the cancer treatment was for prostate cancer or metastatic prostate cancer. 
   
   
       74 . The method of  claim 72 , wherein the male castrate is temporally castrated during or subsequent the cancer treatment. 
   
   
       75 . The method of  claim 72 , wherein the male castrate is permanently castrated during or subsequent the cancer treatment. 
   
   
       76 . The method of  claim 67 , wherein the male castrate has been administered the steroid agent during a treatment to reduce sexual capability. 
   
   
       77 . A method for treating an individual suffering from surgically induced hot flashes or drug induced hot flashes, comprising vomeronasally administering a therapeutically effective dosage of a steroid agent comprising 16α,17α-epoxy-10β-hydroxyestr-4-en-3-one to the individual. 
   
   
       78 - 79 . (canceled) 
   
   
       80 . The method of  claim 77 , wherein the individual is a female individual and suffers hot flashes due to a surgically induced postmenopause. 
   
   
       81 . The method of  claim 77 , wherein the individual is a female individual and lacks completely or a portion of at least one female reproductive organ. 
   
   
       82 . The method of  claim 81 , wherein the at least one female reproductive organ is selected from the group consisting of uterus, ovaries, and fallopian tubes. 
   
   
       83 . The method of  claim 77 , wherein the individual is a female individual and has been administered a hysterectomy. 
   
   
       84 . The method of  claim 77 , wherein the individual is a male individual. 
   
   
       85 . (canceled) 
   
   
       86 . The method of  claim 84 , wherein the hot flashes are drug induced hot flashes. 
   
   
       87 . The method of  claim 86 , wherein the hot flashes are drug induced by the administration of at least one luteinizing hormone releasing hormone antagonist compound to the male individual. 
   
   
       88 . The method of  claim 84 , wherein the male individual is undergoing androgen-dependent therapy. 
   
   
       89 . The method of  claim 87 , wherein the at least one luteinizing hormone releasing hormone antagonist compound is selected from the group consisting of buserelin, goserelin, leuprolide, triptorelin, derivatives thereof, salts thereof, and combinations thereof. 
   
   
       90 . The method of  claim 77 , wherein the hot flashes are drug induced by the administration of at least one estrogen antagonist. 
   
   
       91 . The method of  claim 90 , wherein the at least one estrogen antagonist is selected from the group consisting of fulvestrant, raloxifene, tamoxifen, and toremifine.