Methods and systems for the diagnosis and treatment of androgen disorders

Abstract

The technology described herein is directed to the diagnosis and treatment of androgen disorders and/or deficiencies, e.g. low testosterone.

1 . A method of determining a free testosterone concentration in a biological sample comprising the following steps:
 a) Identifying in the biological sample
 i. A total SHBG concentration, 
 ii. A total testosterone concentration, and 
 iii. An albumin concentration; 
   b) Attributing at least two distinct interconverting micro states of an unliganded SHBG dimer having a first monomer and a second monomer;   c) Calculating the free testosterone concentration in the biological sample using an ensemble allostery model encompassing readjustment of a first equilibria between the microstates upon binding of a first testosterone molecule to the first monomer and an allosteric interaction between two binding sites of the SHBG dimer.   
     
     
         2 . The method of  claim 1 , wherein the step of identifying in the biological sample further comprises identifying in the biological sample
 iv. A concentration of at least one non-testosterone steroid.   
     
     
         3 . The method of  claim 2 , wherein the non-testosterone steroid is selected from the group consisting of an estradiol steroid, an estrone steroid, and a dihydrotestosterone steroid. 
     
     
         4 . The method of  claim 1 , wherein the step of identifying in the biological sample further comprises identifying in the biological sample
 iv. at least one analyte concentration.   
     
     
         5 . The method of  claim 1 , wherein the step of identifying in the biological sample further comprises measuring in the biological sample using at least one analytical method. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the method further comprises the step of: d) using the free testosterone concentration to diagnose a medical disease in men, women, and children. 
     
     
         8 . The method of  claim 7 , wherein the medical disease comprises an androgen disorder. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 8 , wherein the androgen disorder comprises a hyperandrogenic disorder. 
     
     
         11 . The method of  claim 10 , wherein the hyperandrogenic disorder is selected from the group consisting of a polycystic ovary syndrome, an acne disorder, a hirsutism disorder, and an androgenic alopecia disorder. 
     
     
         12 . The method of  claim 1 , wherein the method further comprises the step of:
 d) using the free testosterone concentration to optimize treatment of a medical disease.   
     
     
         13 . The method of  claim 12 , wherein the medical disease comprises an androgen disorder. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 13  wherein the androgen disorder comprises a hyperandrogenic disorder. 
     
     
         16 . The method of  claim 15 , wherein the hyperandrogenic disorder is selected from the group consisting of a polycystic ovary syndrome, an acne disorder, a hirsutism disorder, and an androgenic alopecia disorder. 
     
     
         17 . The method of  claim 1 , wherein the method further comprises the step of:
 d) using the free testosterone concentration to determine the dose and to adjust the dose for a formulation of testosterone for treatment of a medical disease.   
     
     
         18 . The method of  claim 17 , wherein the medical disease is an androgen disorder. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 18 , wherein the androgen disorder is a hyperandrogenic disorder. 
     
     
         21 . The method of  claim 20 , wherein the hyperandrogenic disorder is selected from the group consisting of a polycystic ovary syndrome, an acne disorder, a hirsutism disorder, and an androgenic alopecia disorder. 
     
     
         22 . The method of  claim 2 , wherein the method further comprises the step of:
 e) Calculating a free non-testosterone steroid concentration in the biological sample using the ensemble allostery model encompassing readjustment of a second equilibria between the microstates upon binding of a non-testosterone steroid molecule to the first monomer and an allosteric interaction between two binding sites of the SHBG dimer.   
     
     
         23 . A method of determining a free sex steroid concentration in a biological sample comprising the following steps:
 a) Identifying in the biological sample
 i) A total SHBG concentration, 
 ii) A total sex steroid concentration, and 
 iii) An albumin concentration; 
   b) Attributing at least two distinct interconverting microstates of an unliganded SHBG dimer having a first monomer and a second monomer,   c) Calculating the free sex steroid concentration in the biological sample using an ensemble allostery model encompassing readjustment of a first equilibria between the microstates upon binding of a first sex steroid molecule to the first monomer and an allosteric interaction between two binding sites of the SHBG dimer.   
     
     
         24 . The method of  claim 23 , wherein the sex steroid is selected from the group consisting of a testosterone steroid, an Estradiol steroid, an Estrone steroid, and a dihydrotestosterone steroid.