The effect of recombinant human GH replacement therapy on lipoprotein(a) and other lipid parameters in adults with acquired GH deficiency: results of a double-blind and placebo-controlled trial

Abstract

The effect of GH substitution on serum lipids and lipoproteins, and in particular lipoprotein(a) (Lp(a)), was investigated in 32 adults with postoperative (acquired) GH deficiency as part of a double-blind, placebo-controlled trial. Seventeen men and fifteen women, aged 18-59 years (mean 42 years) from two centres (Hannover and Göttingen) were randomly assigned to two groups. Group P (placebo) received placebo for the first 12 months and recombinant human GH (rhGH) for the following 12 months (open phase). Group V (verum) was treated with rhGH for two consecutive periods of 12 months each. The target dose of rhGH was 2 U/m 2 per day, given subcutaneously daily at bedtime. Serum concentrations of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were determined at 0, 12 and 24 months. In group V, Lp(a) increased significantly in the first as well as in the second year of treatment (P=0.02, 12 months versus baseline; P=0.016, 24 months versus 12 months). In contrast, Lp(a) levels remained unchanged in group P during the first 12 months (P=0.826 versus baseline), but increased significantly (P=0.002) during the second year, when all patients were administered GH. The increase in Lp(a) after 12 months of rhGH replacement therapy in all 32 patients was significant for Lp(a) baseline concentrations both above and below 20 mg/dl and was independent of the apolipoprotein(a) isoforms. Total and LDL-C decreased significantly after 1 year and triglycerides after 2 years in group V. A significant reduction was also observed in the TC/HDL-C and the LDL-C/HDL-C ratios. Our study shows an unfavorable effect of rhGH replacement therapy on Lp(a) levels, which is, however, counteracted by a favorable effect of rhGH on TC, LDL-C and the TC/LDL-C and LDL-C/HDL-C ratios.

Cardiovascular risk factors improve during 3 years of growth hormone therapy in Prader-Willi syndrome

“…There is concern that GH increases the concentration of atherogenic Lp(a) particles [34,35]. In contrast to these shorter term observations, in the present study, levels only rose transiently during GH therapy, and, in the long term, did not signi®cantly increase with GH.…”

“…Several, for the most part controlled, studies have reported favourable lipolytic and anabolic eects of GH treatment in PWS, improving lipid metabolism [11] and body composition during 12 months [16,17,31,32]. While it has also been shown in children with GH de®ciency [28] or Turner syndrome [44], that GH decreases LDL-cholesterol (LDL-C) and increases high density lipoprotein cholesterol (HDL-C) during GH treatment, this favourable eect might be counteracted by an increase in lipoprotein (a) (Lp(a)), which independently is associated with a high risk for arteriosclerosis [34,35]. In addition, the long-term eects of GH on lipid metabolism have not yet been studied in PWS patients.…”

Human Growth Hormone Increases Apo(a) Expression in Transgenic Mice

“…Acromegalics have elevated plasma Lp(a) levels, and successful treatment of this disorder is associated with a decrease in plasma apo(a) levels proportional to the reduction in GH. 16,15,36 GH administration to adult individuals with GH deficiency result in a 30% to 200% increase in plasma Lp(a) levels. 32,37 A significant increase in plasma apo(a) level also occurs when GH is given to normal adults.…”

Deficiência de GH em adultos: resultados do estudo multicêntrico brasileiro

“…Em resposta à reposição de GH, o principal achado é uma redução nos níveis de colesterol total e LDL colesterol, que em alguns dos estudos foi correlacionado com as concentrações basais de LDL colesterol (21,(25)(26)(27)(28). GH aumenta a secreção hepáti-ca de VLDL e induz a expressão de receptores hepáti-cos de LDL, promovendo o clearance de VLDL/LDL da circulação (29)(30)(31).…”