Methods and Compositions for the Treatment of Alopecia and Other Disorders of the Pilosebaceous Apparatus

Abstract

Insulin sensitivity increasing substances (ISIS), including but not limited to D-chiro-inositol, thiazolidinedione and derivatives, and biguanides, are useful in the treatment of hair loss and other disorders of the pilosebaceous apparatus (hirsutism, acne, etc.) associated with conditions of excess insulin and/or insulin resistance. The treatment comprises administering to a mammal, such as a human, at least one ISIS either alone or in combination with at least one agent, such as an androgen receptor blocker (ARB) and/or a steroid enzyme inhibitor or inducer (STI). Additionally, an activity enhancing agent may be included for topical administration.

1 . A method of treating a disorder of the pilosebaceous apparatus of a mammal, comprising administering to the mammal a thiazolidinedione compound in an amount effective to treat the disorder in the mammal, in a manner so as to reach an affected area of the pilosebaceous apparatus.  
   
   
       2 . The method of  claim 1 , wherein the disorder is alopecia.  
   
   
       3 . The method of  claim 2 , wherein treating the disorder comprises at least one of inhibiting, reducing and reversing the loss of hair in the mammal.  
   
   
       4 . The method of  claim 1 , wherein the thiazolidinedione compound is administered topically to the affected site.  
   
   
       5 . The method of  claim 1 , wherein the thiazolidinedione compound is administered orally.  
   
   
       6 . The method of  claim 1 , wherein the mammal is a human.  
   
   
       9 . The method of  claim 1 , wherein the thiazolidinedione compound is selected from the group consisting of troglitazone, ciglitazone, pioglitazone, rosiglitazone and englitazone.  
   
   
       10 . The method of  claim 9 , wherein the thiazolidinedione compound is troglitazone.  
   
   
       11 . The method of  claim 1 , further comprising administering to the mammal a steroid enzyme inhibitor or inducer (STI) in an amount effective to inhibit or induce the activity of a steroid enzyme in the mammal.  
   
   
       12 . The method of  claim 11 , wherein the steroid enzyme inhibitor or inducer (STI) is selected from the group consisting of a 5-alpha reductase inhibitor (ARI), a 3-alpha hydroxy steroid dehydrogenase inhibitor, and a 17-beta hydroxy steroid dehydrogenase inducer.  
   
   
       13 . The method of  claim 1 , further comprising administering to the mammal an androgen receptor blocking agent (ARB) in an amount effective to block androgen receptor activity in the mammal.  
   
   
       14 . The method of  claim 13 , wherein the androgen receptor blocking agent ARB is a steroidal or a non-steroidal compound selected from the group consisting of cytoproterone acetate, flutamide, bicalutamide, nilutamide, RU-58841, canrenone, spironolactone, progesterone, 4MA, ketoconazole, and cimetidine.  
   
   
       15 . The method of  claim 1 , further comprising administering to the mammal both an androgen receptor blocking agent (ARB) in an amount effective to block androgen receptor activity, and a steroid enzyme inhibitor or inducer (STI) in an amount effective to inhibit or induce the activity of a steroidal enzyme in the mammal.  
   
   
       16 . The method of  claim 1 , further comprising administering to the mammal an activity-enhancing agent where either the thiazolidinedione compound alone or in combination with an androgen receptor blocking agent (ARB) or steroid enzyme inhibitor or inducer (STI) is administered topically, wherein the activity-enhancing agent is administered to the mammal in an amount effective to enhance the activity of either the thiazolidinedione compound alone or in combination with the androgen receptor blocking agent (ARB) and at least one of the steroid enzyme inhibitor and inducer (STI).  
   
   
       17 . The method of  claim 16 , wherein the activity-enhancing agent comprises at least one substance selected from the group consisting of a penetration-enhancing agent, a vasodilator compound, an anti-inflammatory agent, a glucose/insulin regulating compound, and an endogenous or exogenous effector.