Methods for treating postmenopausal women using ultra-low doses of estrogen

Abstract

The present invention provides methods for treating physical conditions resulting from postmenopausal estrogen decline in a postmenopausal subject, and in particular methods for reducing the risk of osteoporotic bone fractures in a postmenopausal subject. The present invention also provides a kit useful for carrying out the methods of the present invention.

1 . A method for treating a physical condition resulting from estrogen decline in a postmenopausal subject, the method comprising administering to the subject an amount of estrogen which is effective to produce a resulting serum level of the estrogen in the subject that is equivalent to a serum estradiol level in the subject of not more than about 20 pg/ml, wherein:
 the estrogen is administered orally, parenterally, or transdermally;   the physical condition is selected from the group consisting of osteoporosis, headaches, nausea, depression, hot flashes, decrease in bone mineral density, and increased risk or incidence of bone fracture; and   the resulting serum level of the estrogen is responsive to the administering of the estrogen.   
     
     
         2 . The method of  claim 1 , wherein the administration of the estrogen does not substantially increase the risk of endometrial or breast cancer in the postmenopausal subject. 
     
     
         3 . The method of  claim 1 , comprising administering to the subject an amount of estrogen which is effective to produce a resulting serum level of the estrogen in the subject that is equivalent to a serum estradiol level of between about 5 pg/ml and about 15 pg/ml. 
     
     
         4 . The method of  claim 1 , wherein the physical condition is selected from the group consisting of postmenopausal estrogen decline, increased risk of osteoporotic bone fracture due to postmenopausal osteoporosis, and loss of bone mineral density. 
     
     
         5 . The method of  claim 1 , wherein the amount of estrogen which is administered is effective to produce a serum level of the estrogen equivalent to a serum estradiol level in the subject of between about 5 pg/ml and about 10 pg/ml. 
     
     
         6 . The method of  claim 1 , comprising transdermally administering less than about 25 μg of estrogen per day to the subject, orally administering between about 0.08 and about 0.19 mg of estrogen per day to the subject, or parenterally administering less than about 20 μg per day of estrogen per day to the subject. 
     
     
         7 . A method for reducing the risk of osteoporotic bone fracture in a subject afflicted with or susceptible to postmenopausal osteoporosis, the method comprising transdermally administering less than about 25 μg of estrogen per day to the subject in the substantial absence of exogenous progestin. 
     
     
         8 . The method of  claim 7 , comprising transdermally administering less than about 20 μg of estrogen per day to the subject. 
     
     
         9 . The method of  claim 7 , wherein the postmenopausal subject comprises a woman having a uterus and ovaries. 
     
     
         10 . The method of  claim 7 , wherein the estrogen comprises 17-β-estradiol. 
     
     
         11 . The method of  claim 7 , comprising the step of testing the serum estradiol level of the subject prior to administration of the estrogen, and determining that the serum estradiol level of the subject to be treated is normal for postmenopausal women in the same age group as the subject. 
     
     
         12 . The method of  claim 7 , wherein the transdermal administration of estrogen to the subject is effective to produce a resulting serum level of the estrogen in the subject that is equivalent to a serum estradiol level in the subject of not more than about 20 pg/ml. 
     
     
         13 . A method for treating a physical condition resulting from postmenopausal estrogen decline in a postmenopausal subject, the method comprising transdermally administering less than about 25 μg of estrogen per day to the subject, orally administering between about 0.08 and about 0.19 mg of estrogen per day to the subject, or parenterally administering less than about 20 μg per day of estrogen per day to the subject, in the substantial absence of exogenous progestin. 
     
     
         14 . The method of  claim 13 , wherein the physical condition is selected from the group consisting of postmenopausal estrogen decline, increased risk of osteoporotic bone fracture due to postmenopausal osteoporosis, and loss of bone mineral density. 
     
     
         15 . The method of  claim 13 , comprising transdermally administering less than about 20 μg of estrogen per day to the subject. 
     
     
         16 . The method of  claim 13 , wherein the postmenopausal subject comprises a woman having a uterus and ovaries. 
     
     
         17 . The method of  claim 13 , wherein the estrogen comprises 17-β-estradiol. 
     
     
         18 . The method of  claim 13 , comprising the step of testing the serum estradiol level of the subject prior to administration of the estrogen, and determining that the serum estradiol level of the subject to be treated is normal for postmenopausal women in the same age group as the subject. 
     
     
         19 . The method of  claim 13 , wherein the administration of estrogen to the subject is effective to produce a resulting serum level of the estrogen in the subject that is equivalent to a serum estradiol level in the subject of not more than about 20 pg/ml. 
     
     
         20 . The method of  claim 13 , comprising transdermally administering the estrogen to the subject via a transdermal patch that delivers the estrogen in an amount that is equivalent to about 14 μg of 17 β-estradiol per day.