title: The relationship between reduced testosterone, stimulated growth hormone secretion and increased carotid intima-media thickness in obese men.
abstract: OBJECTIVE
  Obesity is associated with reduced testosterone and growth hormone (GH). However, the interrelationship between these axes and their independent contributions to cardiovascular risk is unknown. The objectives of this study were to determine (1) the association between testosterone and GH in obesity, (2) whether excess adiposity mediates this association and (3) the relative contribution of reduced testosterone and GH to increased carotid intima-media thickness (cIMT) in obesity.
  
  
  METHODS
  Fifty obese men were studied with GH-releasing hormone-arginine testing, and morning free testosterone (FT) was measured by equilibrium dialysis. Metabolic, anthropometric and cardiovascular risk indices, including cIMT were measured. Twenty-six normal weight men served as controls.
  
  
  RESULTS
  Obese subjects demonstrated lower mean (±SEM) peak stimulated GH (5·9 ± 0·6 vs 36·4 ± 3·9 μg/l; P < 0·0001) and FT (0·41 ± 0·03 vs 0·56 ± 0·03 nmol/l; P = 0·0005) compared to controls. GH was significantly associated with FT (r = +0·44; P < 0·0001) and both were inversely related to visceral adipose tissue (VAT) (GH: r = -0·65; P < 0·0001; FT: r = -0·51; P < 0·0001). In multivariate regression analysis controlling for VAT, FT was no longer related to GH. Both GH and FT were associated with cIMT in univariate analysis. However, in multivariate modelling including traditional cardiovascular risk markers, GH (β = 0·003; P = 0·04) but not FT (P = 0·35) was associated with cIMT.
  
  
  CONCLUSIONS
  These results demonstrate a strong relationship between FT and GH in obesity and suggest that this relationship is more a function of excess adiposity rather than a direct relationship. While reduced FT and GH are both related to increased cIMT, the relationship with reduced GH remains significant controlling for reduced FT and traditional cardiovascular disease risk markers.
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School Boston Heart Foundation, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Hideo
authors.initials: H
authors.lastname: Makimura
authors.forename: Takara L
authors.initials: TL
authors.lastname: Stanley
authors.forename: Noelle
authors.initials: N
authors.lastname: Sun
authors.forename: Jean M
authors.initials: JM
authors.lastname: Connelly
authors.forename: Linda C
authors.initials: LC
authors.lastname: Hemphill
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D000328:Adult; D001120:Arginine; D002318:Cardiovascular Diseases / Q000209:etiology; D002339:Carotid Arteries / Q000473:pathology*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D012306:Risk; D013739:Testosterone / Q000378:metabolism*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology*; D014463:Ultrasonography
chemical_list: D019382:Human Growth Hormone; D013739:Testosterone; D001120:Arginine