Methods of treating testosterone deficiency

Abstract

Methods of treating a testosterone deficiency or its symptoms with a pharmaceutical formulation of testosterone undecanoate are provided.

What is claimed is: 
     
         1 . A method of treating conditions associated with a deficiency or absence of endogenous testosterone in a subject in need thereof comprising the steps of:
 administering to the subject a defined dose of an oral pharmaceutical composition comprising testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant, wherein the defined dose is 198 mg administered twice daily;   collecting a blood sample from the subject;   measuring the serum testosterone concentration in the subject; and   increasing the dose of testosterone undecanoate to 237 mg, administered twice daily, when the measured serum testosterone concentration in the subject is less than about 425 ng/dL,   decreasing the dose of testosterone undecanoate to 158 mg, administered twice daily, when the measured serum testosterone concentration in the subject is greater than about 970 ng/dL, or   maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration in the subject is between about 425 ng/dL and about 970 ng/dL.   
     
     
         2 . The method of  claim 1 , wherein the serum testosterone concentration is measured four to eight hours after administering the oral pharmaceutical composition. 
     
     
         3 . The method of  claim 1 , wherein the oral pharmaceutical composition comprises about 19.8 percent by weight of solubilized testosterone undecanoate, about 51.6 percent by weight of oleic acid, and about 16.1 percent by weight of polyoxyethylene (40) hydrogenated castor oil. 
     
     
         4 . The method of  claim 3 , wherein the oral pharmaceutical composition further comprises about 10 percent by weight of borage seed oil and about 2.5 percent by weight of peppermint oil. 
     
     
         5 . The method of  claim 1 , wherein the testosterone concentrations are measured in serum from a blood sample collected in a plain tube drawn 5-7 hours after the morning dose and at least 7 days after starting treatment and following dose adjustment. 
     
     
         6 . The method of  claim 1 , wherein the subject is diagnosed with primary hypogonadism. 
     
     
         7 . The method of  claim 1 , wherein the subject is diagnosed with hypogonadotropic hypogonadism. 
     
     
         8 . The method of  claim 7 , wherein the subject is diagnosed with gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. 
     
     
         9 . The method of  claim 1 , wherein prior to administering the defined dose of an oral pharmaceutical composition, further comprising the step of confirming the diagnosis of hypogonadism. 
     
     
         10 . The method of  claim 9 , wherein the diagnosis of hypogonadism is confirmed if the serum testosterone concentrations measured on at least two separate days are below the normal range. 
     
     
         11 . A method of treating conditions associated with a deficiency or absence of endogenous testosterone in a subject in need thereof comprising the steps of:
 administering to the subject a defined dose of an oral pharmaceutical composition comprising testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant, wherein the defined dose is 396 mg administered twice daily;   collecting a blood sample from the subject;   measuring the serum testosterone concentration in the subject; and   decreasing the dose of testosterone undecanoate to 316 mg, administered twice daily, when the measured serum testosterone concentration in the subject is greater than about 970 ng/dL, or   maintaining the dose of testosterone undecanoate when the measured serum testosterone concentration in the subject is between about 425 ng/dL and about 970 ng/dL.   
     
     
         12 . The method of  claim 11 , wherein the serum testosterone concentration is measured four to eight hours after administering the oral pharmaceutical composition. 
     
     
         13 . The method of  claim 11 , wherein the oral pharmaceutical composition comprises about 19.8 percent by weight of solubilized testosterone undecanoate, about 51.6 percent by weight of oleic acid, and about 16.1 percent by weight of polyoxyethylene (40) hydrogenated castor oil. 
     
     
         14 . The method of  claim 13 , wherein the oral pharmaceutical composition further comprises about 10 percent by weight of borage seed oil and about 2.5 percent by weight of peppermint oil. 
     
     
         15 . The method of  claim 11 , wherein the testosterone concentrations are measured in serum from a blood sample collected in a plain tube drawn 5-7 hours after the morning dose and at least 7 days after starting treatment and following dose adjustment. 
     
     
         16 . The method of  claim 11 , wherein the subject is diagnosed with primary hypogonadism. 
     
     
         17 . The method of  claim 11 , wherein the subject is diagnosed with hypogonadotropic hypogonadism. 
     
     
         18 . The method of  claim 17 , wherein the subject is diagnosed with gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. 
     
     
         19 . The method of  claim 11 , wherein prior to administering the defined dose of an oral pharmaceutical composition, further comprising the step of confirming the diagnosis of hypogonadism. 
     
     
         20 . The method of  claim 11 , wherein the diagnosis of hypogonadism is confirmed if the serum testosterone concentrations measured on at least two separate days are below the normal range. 
     
     
         21 . A method of treating conditions associated with a deficiency or absence of endogenous testosterone in a subject in need thereof comprising the steps of:
 administering to the subject a defined dose of an oral pharmaceutical composition comprising testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant, wherein the defined dose is 158 mg administered twice daily;   collecting a blood sample from the subject;   measuring the serum testosterone concentration in the subject; and   increasing the dose of testosterone undecanoate to 198 mg, administered twice daily, when the measured serum testosterone concentration in the subject is less than about 425 ng/dL, and   treatment is discontinued when the subject's measured serum testosterone concentration in the subject is greater than about 970 ng/dL.   
     
     
         22 . The method of  claim 21 , wherein the serum testosterone concentration is measured four to eight hours after administering the oral pharmaceutical composition. 
     
     
         23 . The method of  claim 21 , wherein the oral pharmaceutical composition comprises about 19.8 percent by weight of solubilized testosterone undecanoate, about 51.6 percent by weight of oleic acid, and about 16.1 percent by weight of polyoxyethylene (40) hydrogenated castor oil. 
     
     
         24 . The method of  claim 23 , wherein the oral pharmaceutical composition further comprises about 10 percent by weight of borage seed oil and about 2.5 percent by weight of peppermint oil. 
     
     
         25 . The method of  claim 21 , wherein the testosterone concentrations are measured in serum from a blood sample collected in a plain tube drawn 5-7 hours after the morning dose and at least 7 days after starting treatment and following dose adjustment. 
     
     
         26 . The method of  claim 21 , wherein the subject is diagnosed with primary hypogonadism. 
     
     
         27 . The method of  claim 21 , wherein the subject is diagnosed with hypogonadotropic hypogonadism. 
     
     
         28 . The method of  claim 27 , wherein the subject is diagnosed with gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. 
     
     
         29 . The method of  claim 21 , wherein prior to administering the defined dose of an oral pharmaceutical composition, further comprising the step of confirming the diagnosis of hypogonadism. 
     
     
         30 . The method of  claim 21 , wherein the diagnosis of hypogonadism is confirmed if the serum testosterone concentrations measured on at least two separate days are below the normal range.