The effect of growth hormone on low-density lipoprotein cholesterol and lipoprotein (a) levels in familial hypercholesterolemia.
Severe elevations of low-density lipoprotein (LDL) cholesterol are not always normalized with conventional drugs. Growth hormone decreases LDL cholesterol levels, in part by augmenting liver LDL receptor activity. This increase may be on the order of magnitude of the increase induced by statins. We investigated the effect of growth hormone in familial hypercholesterolemia (FH) in a randomized, double-blind, placebo-controlled study. Thirty-one men with FH aged 20 to 48 years, of whom 81% had a known LDL receptor gene mutation, discontinued all lipid-lowering drugs 6 weeks before the study. Dietary stabilization continued for 5 more weeks, followed by single-blind placebo injections for 1 week. Thereafter, 16 subjects were allocated to recombinant growth hormone 0.05 IU/kg/d and 15 to placebo injected subcutaneously for 12 weeks. Baseline lipid levels were similar in both groups. One subject in the growth hormone group withdrew after 8 weeks due to shoulder pain. Mean compliance among the rest of the subjects was 98%. The mean change in LDL cholesterol was -0.46 mmol/L (95% confidence interval [CI], -1.00 to 0.09 mmol/L) in the growth hormone group versus 0.08 mmol/L (95% CI, -0.55 to 0.71 mmol/L) in the placebo group (difference not significant). No changes occurred in the levels of other lipids, lipoprotein particles, or apolipoproteins, with the exception of lipoprotein(a) [Lp(a)]. The median changes in Lp(a) were 33% (interquartile range, 2% to 53%) and -15% (interquartile range, -22% to 18%) in the growth hormone and placebo groups, respectively (P = .02). We conclude that the effect of growth hormone on LDL cholesterol levels in FH is less than expected, based on its LDL-catabolic effects, and is counteracted by profound increases in Lp(a) levels, resulting in unchanged levels of apolipoprotein B. Thus, growth hormone is probably not useful as adjunctive therapy in FH.
Tonstad
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S
Medical Department A, National Hospital, Oslo, Norway.
Sundt
E
E
Ose
L
L
Hagve
T A
TA
Fruchart
J C
JC
Bard
J M
JM
Edén
S
S
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone