Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: A randomized controlled trial

GH deficiency is associated with increased cardiovascular mortality and ear ly manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The ef fect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind , placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo f or 18 months. with dose adjustments made according to serum insulin-like gr owth factor I(IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T-3 levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T,, thy roid hormone binding index, and free T, index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 mu mol/L; confidence interval, -2.4, -0.02 mu mol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T, increased in the GH-treated group us. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confid ence interval. 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 leve ls did not significantly change between groups. Changes in homocyst(e)ine w ere negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 r 0.02 mu mol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in fola te, vitamin B12, total T-3, C-reactive protein, interleukin-6, or insulin l evels. This study shows that GH replacement decreases fasting homocyst(e)in e levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement.