Methods of treating testosterone deficiency

Abstract

Methods of treating a testosterone deficiency or its symptoms with a pharmaceutical formulation of testosterone esters are provided. In some embodiments, the subject has adequately controlled blood pressure.

1 - 26 . (canceled) 
     
     
         27 . A method of treating one or more conditions associated with a deficiency or absence of endogenous testosterone in a subject, comprising:
 administering a defined dose of testosterone undecanoate selected from 158 mg, 198 mg, 237 mg, 316 mg and 396 mg to the subject in an oral pharmaceutical composition twice daily, once in the morning and once in the evening;   measuring serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the defined dose and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate when the defined dose is 158 mg, 198 mg, 237 mg, or 316 mg, and when the measured serum testosterone concentration is less than about 425 ng/dL, 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate when the defined dose is 198 mg, 237 mg, or 316 mg, or 396 mg, or discontinuing treatment when the defined dose is 158 mg, when the measured serum testosterone concentration is greater than about 970 ng/dL; 
 wherein the oral pharmaceutical composition comprises the testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant. 
   
     
     
         28 . The method of  claim 27 , wherein the maximum defined dose is 396 mg administered twice daily. 
     
     
         29 . The method of  claim 27 , wherein the measuring is performed from serum collected in a plain tube. 
     
     
         30 . The method of  claim 27 , wherein the one or more conditions are selected from primary hypogonadism and hypogonadotropic hypogonadism. 
     
     
         31 . The method of  claim 30 , wherein the one or more conditions is hypogonadotropic hypogonadism caused by gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. 
     
     
         32 . The method of  claim 27 , wherein the defined dose is 158 mg and either:
 the dose of testosterone undecanoate is increased to 198 mg when the serum testosterone concentration is less than about 425 ng/dL; or   the administration of testosterone undecanoate is discontinued when the serum testosterone concentration is greater than about 970 ng/dL.   
     
     
         33 . The method of  claim 32 , wherein the dose of testosterone undecanoate is increased to 198 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the increased dose of 198 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 237 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 158 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         34 . The method of  claim 27 , wherein the defined dose is 198 mg and either:
 the dose of testosterone undecanoate is increased to 237 mg when the serum testosterone concentration is less than about 425 ng/dL; or   the dose of testosterone undecanoate is decreased to 158 mg when the serum testosterone concentration is greater than about 970 ng/dL.   
     
     
         35 . The method of  claim 34 , wherein the dose of testosterone undecanoate is increased to 237 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the increased dose of 237 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 316 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 198 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         36 . The method of  claim 34 , wherein the dose of testosterone undecanoate is decreased to 158 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the decreased dose of 158 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 198 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 discontinuing treatment when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         37 . The method of  claim 27 , wherein the defined dose is 237 mg and either:
 the dose of testosterone undecanoate is increased to 316 mg when the serum testosterone concentration is less than about 425 ng/dL; or   the dose of testosterone undecanoate is decreased to 198 mg when the serum testosterone concentration is greater than about 970 ng/dL.   
     
     
         38 . The method of  claim 37 , wherein the dose of testosterone undecanoate is increased to 316 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the increased dose of 316 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 396 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 237 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         39 . The method of  claim 37 , wherein the dose of testosterone undecanoate is decreased to 198 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the decreased dose of 198 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 237 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 158 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         40 . The method of  claim 27 , wherein the defined dose is 316 mg and either:
 the dose of testosterone undecanoate is increased to 396 mg when the serum testosterone concentration is less than about 425 ng/dL; or   the dose of testosterone undecanoate is decreased to 237 mg when the serum testosterone concentration is greater than about 970 ng/dL.   
     
     
         41 . The method of  claim 40 , wherein the dose of testosterone undecanoate is increased to 396 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the increased dose of 396 mg and 6 hours after administration of a morning dose; and   either: 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 316 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         42 . The method of  claim 40 , wherein the dose of testosterone undecanoate is decreased to 237 mg and the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the decreased dose of 237 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 316 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 198 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         43 . The method of  claim 27 , wherein the defined dose is 396 mg, and the dose of testosterone undecanoate is decreased to 316 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
     
     
         44 . The method of  claim 43 , wherein the method further comprises:
 remeasuring the serum testosterone concentration in the subject at steady state after at least seven days of daily administration of the decreased dose of 316 mg and 6 hours after administration of a morning dose; and   either: 
 increasing the dose of testosterone undecanoate to 396 mg when the serum testosterone concentration is less than about 425 ng/dL; 
 maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration is between about 425 ng/dL and about 970 ng/dL; or 
 decreasing the dose of testosterone undecanoate to 237 mg when the serum testosterone concentration is greater than about 970 ng/dL. 
   
     
     
         45 . The method of  claim 27 , wherein the ratio (w/w) in the composition of total lipophilic surfactant to total hydrophilic surfactant is in the range of about 6:1 to about 3.5:1. 
     
     
         46 . The method of  claim 27 , wherein the lipophilic surfactant is a fatty acid. 
     
     
         47 . The method of  claim 27 , wherein the hydrophilic surfactant is a hydrogenated castor oil ethoxylate. 
     
     
         48 . The method of  claim 27 , wherein the oral pharmaceutical composition comprises a digestible oil. 
     
     
         49 . The method of  claim 27 , wherein the lipophilic surfactant is oleic acid and the hydrophilic surfactant is polyoxyethylene (40) hydrogenated castor oil. 
     
     
         50 . The method of  claim 49 , wherein the oral pharmaceutical composition further comprises borage seed oil and peppermint oil. 
     
     
         51 . The method of  claim 27 , wherein the subject has adequately controlled blood pressure.