Early Cardiovascular and Metabolic Benefits of rhGH Therapy in Adult Patients with Severe Growth Hormone Deficiency: Impact on Oxidative Stress Parameters

Abstract

It is hypothesized that growth hormone deficiency (GHD) is associated with increased oxidative stress (OS), contributing to elevated cardiovascular risk. This preliminary study evaluates changes in OS markers and cardiovascular biomarkers in 15 adult patients with severe GHD undergoing 12 months of recombinant human growth hormone (rhGH) therapy. IGF-1 concentrations increased significantly following 6 and 12 months of therapy (p = 0.0003 and p = 0.0001, respectively). These changes were accompanied by a significant decrease in endothelin-1 (ET-1) levels at 12 months (p = 0.007), as well as reductions in asymmetric dimethylarginine (ADMA) levels at both 6 and 12 months (p = 0.01 for each timepoint). Total oxidative capacity (TOC) decreased significantly after 6 months of therapy (p = 0.02), followed by a significant increase at 12 months (p = 0.04), whereas total antioxidant capacity (TAC) showed a significant increase at 12 months (p = 0.02). Tissue fat % showed significant reductions at 6 months (p = 0.006), suggesting early improvements in body composition. Correlation analyses indicated negative associations between IGF-1 and TOC (p < 0.006; R = -0.73), and positive associations with TAC (p < 0.001; R = 0.83). These findings suggest that rhGH therapy in adult patients with severe GHD reduces OS and cardiovascular risk through the modulation of biomarkers and improved body composition. This study explores the role of rhGH therapy in reducing cardiovascular risks in GHD, emphasizing the importance of individualized treatment approaches.

Keywords: asymmetric dimethyl arginine; endothelin-1; growth hormone; growth hormone deficiency; oxidative stress.

Figure 1

Changes in serum insulin-like growth factor type 1 (IGF-1) concentrations during rhGH therapy in patients with growth hormone deficiency (GHD). A significant increase in IGF-1 levels was observed after 6 months (V1) (p = 0.003 *) and maintained after 12 months (V2) of treatment compared to baseline (V0) (p = 0.0001 ***). However, no statistically significant difference was found between the 6- and 12-month timepoints (p = 0.15 **). Values are shown as box plots with median, interquartile range, and full range.

Figure 2

Effect of rhGH therapy on endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), total oxidant capacity (TOC), and total antioxidant capacity (TAC) levels in patients with growth hormone deficiency (GHD). After 12 months of treatment (V2), ET-1 concentrations were significantly reduced compared to baseline (V0) (p = 0.007 *), while no significant change was seen at 6 months (V1). ADMA levels showed a significant decrease as early as V1, which persisted through V2 (p = 0.01) **, ***). TOC levels were significantly lower at both V1 and V2 (p = 0.02 ****, and p = 0.04 *****, respectively), indicating reduced oxidative stress. In contrast, TAC levels showed a significant increase at V2 (p = 0.02 ******), suggesting improved antioxidant capacity. Box plots represent median values with interquartile ranges and full data spread.