We investigated the influence of gender and apoE and apo(a) phenotypes as well as the effect of the metabolic effects of growth hormone (GH) on the effect of GH therapy on serum lipoprotein concentrations in GH-deficient (GHD) adults. Forty-four consecutive patients, 30 men and 14 women aged 46.5 (range, 19 to 76) years with GHD due mainly to pituitary tumors, were treated with recombinant human GH for 12 months. Serum concentrations of lipoproteins, insulin, thyroxine, and insulin-like growth factor-I were determined, body composition was assessed by bioelectrical impedance, and apo(a) and apoE phenotypes were analyzed. Lipoprotein(a) [Lp(a)] concentrations in the GHD subjects were compared with a gender- and apo(a) phenotype-matched control group. After 12 months of GH treatment, the total cholesterol, LDL cholesterol, and apoB concentrations decreased, the HDL cholesterol and apoE concentrations increased, and the apoA-I and triglyceride concentrations were unchanged. Before treatment, the Lp(a) concentration was similar to that in the control group. However, after 12 months of treatment, the Lp(a) concentration had increased by 44% and 101% above baseline and the control group, respectively. Men and women responded differently to GH, with a more marked increase in Lp(a) concentration and fat-free mass and a more pronounced decrease in body-fat mass in men. Apo(a) phenotypes had no major influence on the effect of GH therapy. The only significant difference between apoE phenotypes was a higher baseline Lp(a) concentration among apoE4 heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)