G. Sesmilo et al., Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: A randomized controlled trial, J CLIN END, 86(4), 2001, pp. 1518-1524
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.