Methods and compositions for treating benign gynecological disorders

Abstract

An improvement in a method of treating benign gynecological disorders is described. In the method, treatment of a benign gynecological disorder with a composition comprised of a gonadotropin releasing hormone (GnRH) compound and an estrogenic compound, and optionally, an androgenic compound, is extended to premenopausal women who are not receiving an exogenously supplied progestin on a regular or periodic basis. Treatment in accord with the invention does not increase significantly the risk of endometrial hyperplasia. The method is also suitable for contraception.

1 . A method of treating benign gynecological disorders in a patient population composed of premenopausal women having no history of endometrial hyperplasia, and who are not receiving exogenously supplied progesterone on a regular or periodic basis, comprising 
 administering by daily intranasal administration, over an extended period of time between about 6 and 12 months, a formulation containing a GnRH compound, in an amount effective to suppress ovarian estrogen and progesterone production, and an estrogenic compound in an amount effective to prevent signs and symptoms of estrogen deficiency.    
     
     
         2 . The method of  claim 1 , wherein the GnRH compound is selected from the group consisting of deslorelin, leuprolide, nafarelin, goserelin, decapeptyl, buserelin, histrelin, gonadorelin, abarelix, cetrorelix, azaline B, and degarelix.  
     
     
         3 . The method of  claim 2 , wherein said formulation is an aqueous formulation, and said administering is effective to deliver a daily spray volume between 30 μL and 200 μL.  
     
     
         4 . The method of  claim 3 , wherein the spray volume administered includes between 0.15 mg and 0.6 mg of 17β-estradiol.  
     
     
         5 . The method of  claim 4 , wherein said administering further includes administering an androgen in an amount sufficient to prevent signs and symptoms of androgen deficiency.  
     
     
         6 . The method of  claim 5 , wherein the androgen is testosterone in an amount between 0.15 mg and 1 mg.  
     
     
         7 . The method of  claim 4 , wherein said spray volume further includes 2-hydroxypropyl-β-cyclodextrin, in a mole ratio of cyclodextrin to total steroid of between 1:1 and 3:1.  
     
     
         8 . The method of  claim 1 , wherein said formulation is an aerosolizable dry powder.  
     
     
         9 . The method of  claim 8 , wherein the dry powder also includes testosterone, in a mole ratio of estrogenic compound: testosterone of between 1:1 and 1:2.