title: Low estradiol concentrations in men with subnormal testosterone concentrations and type 2 diabetes.
abstract: OBJECTIVE
  It has been suggested that the high prevalence of subnormal free testosterone concentrations, along with low or inappropriately normal gonadotropins in men with type 2 diabetes, may be the result of an increase in plasma estradiol concentrations secondary to an increase in aromatase activity in the adipose tissue that leads to the suppression of the hypothalamo-hypophyseal-gonadal axis.
  
  
  METHODS
  To investigate this hypothesis, plasma estradiol, testosterone, leutinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin (SHBG) concentrations were measured in fasting blood samples of 240 men with type 2 diabetes. Free estradiol concentrations were either calculated (n = 198) using total estradiol and SHBG measured by immunoassay or directly measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and equilibrium dialysis (n = 102).
  
  
  RESULTS
  The calculated free estradiol concentration in men with subnormal free testosterone concentrations was lower than that in men with normal free testosterone concentrations (median 0.047 vs. 0.063 ng/dL, P < 0.001). Directly measured (LC-MS/MS) free estradiol concentrations were also lower in men with subnormal free testosterone concentrations (median 0.025 vs. 0.045 ng/dL, P = 0.008). Free estradiol concentrations were directly related to free testosterone but not to BMI or age.
  
  
  CONCLUSIONS
  These data show that the suppression of the hypothalamo-hypophyseal-gonadal axis in patients with subnormal free testosterone concentrations and type 2 diabetes is not associated with increased estradiol concentrations. The pathogenesis of subnormal free testosterone concentrations in type 2 diabetes needs to be investigated further.
authors.affiliation: State University of New York at Buffalo,Buffalo, NY, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dhindsa
authors.forename: Richard
authors.initials: R
authors.lastname: Furlanetto
authors.forename: Mehul
authors.initials: M
authors.lastname: Vora
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Ajay
authors.initials: A
authors.lastname: Chaudhuri
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
mesh_terms: D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood*
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone