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.

Design: 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.

Trial registration: ClinicalTrials.gov NCT00562796.

Fig. 1

(a) Univariate regression analysis of peak growth hormone (GH) on GH-releasing hormone (GHRH)–arginine stimulation test and free testosterone (FT) by equilibrium dialysis. Normal weight subjects are depicted by open circles while obese subjects are depicted by closed squares. (b) FT levels stratified by GH status. GH sufficiency or relative GH deficiency was determined by peak stimulated GH ≤4·2 µg/l on standard GHRH–arginine stimulation test. Statistical significance was determined by anova.

Fig. 2

Univariate regression analysis of free testosterone by equilibrium dialysis and carotid intima-media thickness (cIMT). Normal weight subjects are depicted by open circles while obese subjects are depicted by closed squares.