Treatment of menopause associated symptoms

Abstract

Described are estradiol-containing pharmaceutical compositions and, and methods using the same to alleviate menopause-related symptoms, such as hot flushes, by topically administering estradiol at low effective doses.

1 . A method of alleviating at least one menopause-associated symptom in a female patient in need thereof, comprising topically administering to said patient an amount of a composition comprising estradiol effective to administer an estradiol dose of about 0.25-0.42 mg/day.  
   
   
       2 . The method of  claim 1 , wherein the estradiol dose is about 0.35-0.40 mg/day.  
   
   
       3 . The method of  claim 1 , wherein the estradiol dose is about 0.375 mg/day.  
   
   
       4 . The method of  claim 1 , wherein the menopause-associated symptom is selected from the group consisting of vasomotor symptoms, vulvar atrophy, vaginal atrophy, and combinations thereof.  
   
   
       5 . The method of  claim 1 , wherein the menopause-associated symptom is hot flushes.  
   
   
       6 . The method of  claim 1 , wherein the method is effective to achieve at least one effect selected from the group consisting of decreasing the severity of vasomotor symptoms, decreasing the frequency of vasomotor symptoms, decreasing the severity of vulvar atrophy, decreasing the severity of vaginal atrophy, and combinations thereof.  
   
   
       7 . The method of  claim 1 , wherein the composition is a hydroalcoholic gel that comprises (i) about 0.025-0.035% (w/w) estradiol, (ii) about 0.1-1.5% (w/w) gelling agent, (iii) about 30-50% (w/w) C2-C6 alcohol, and (iv) water.  
   
   
       8 . The method of  claim 7 , wherein the gelling agent comprises at least one polyacrylic acid.  
   
   
       9 . The method of  claim 8 , wherein the gelling agent comprises at least one carbomer.  
   
   
       10 . The method of  claim 9 , wherein the gelling agent comprises at least one selected from the group consisting of Carbopol® 980, Carbopol® 934P, Carbopol® 1342, Carbopol® 1382, and mixtures thereof.  
   
   
       11 . The method of  claim 7 , wherein the composition comprises (i) about 0.03% (w/w) estradiol, (ii) about 0.5-1% (w/w) polyacrylic acid polymer, (iii) about 40% (w/w) absolute ethanol, and (iv) water.  
   
   
       12 . The method of  claim 1 , wherein the composition is a hydroalcoholic gel that comprises (i) about 0.03% (w/w) estradiol; and (ii) about 40% (w/w) absolute ethanol, wherein said composition has a Brookfield viscosity at 20° C. of between 30-120 Pa.s.  
   
   
       13 . The method of  claim 12 , wherein said Brookfield viscosity is 35-100 Pa.s.  
   
   
       14 . The method of  claim 12 , wherein said Brookfield viscosity is 50-60 Pa.s.  
   
   
       15 . A hydroalcoholic gel composition suitable for topical administration comprising (i) about 0.025-0.035% (w/w) estradiol, (ii) about 0.1-1.5% (w/w) gelling agent, (iii) about 30-50% (w/w) C2-C6 alcohol, and (iv) water.  
   
   
       16 . The composition of  claim 15 , wherein the gelling agent comprises at least one polyacrylic acid.  
   
   
       17 . The composition of  claim 16 , wherein the gelling agent comprises at least one carbomer.  
   
   
       18 . The composition of  claim 17 , wherein the gelling agent comprises at least one selected from the group consisting of Carbopol® 980, Carbopol® 934P, Carbopol® 1342, Carbopol® 1382, and mixtures thereof.  
   
   
       19 . The composition of  claim 15 , wherein the composition comprises (i) about 0.03% (w/w) estradiol, (ii) about 0.5-1% (w/w) polyacrylic acid polymer, (iii) about 40% (w/w) absolute ethanol, and (iv) water.  
   
   
       20 . A hydroalcoholic gel composition suitable for topical administration comprising (i) about 0.03% (w/w) estradiol; and (ii) about 40% (w/w) absolute ethanol, wherein said composition has a Brookfield viscosity at 20° C. of between 30-120 Pa.s.  
   
   
       21 . The composition of  claim 20 , wherein said Brookfield viscosity is 35-100 Pa.s.  
   
   
       22 . The composition of  claim 21 , wherein said Brookfield viscosity is 50-60 Pa.s.  
   
   
       23 . A unit dose composition suitable for topical administration comprising about 0.25-0.42 mg estradiol.  
   
   
       24 . The unit dose composition of  claim 23 , comprising about 0.35-0.40 mg estradiol.  
   
   
       25 . The unit dose composition of  claim 23 , comprising about 0.375 mg estradiol.