Effect of 5 Years of GH Replacement on Atherosclerosis
Status:
Completed
Trial end date:
2006-12-01
Target enrollment:
Participant gender:
Summary
Adult patients with hypopituitarism under adequate conventional hormone replacement therapy
have reduced life expectancy due to excess vascular events (1-4). Deficiency in GH secretion
(GHD) is likely to play a major role in determining the excess mortality, since it is
associated with lipid abnormalities, visceral adiposity, glucose intolerance, insulin
resistance, hypertension, cardiac abnormalities and increased intima-media thickness (IMT) at
major arteries (5).
Beneficial effects of growth hormone (GH) replacement on cardiovascular risk factors have
been demonstrated in several studies of hypopituitary GHD patients (5). GH replacement
improves body composition and lipid profile (5): it is accepted that management of
dyslipidaemia is crucial in primary and secondary prevention of cardiovascular disease and
part of the excess vascular risk associated with hypopituitarism is likely to be due to
dyslipidaemia (6). A meta-analysis of blinded, randomized, placebo-controlled trials with low
doses and long-duration GH treatment showed that GH replacement has beneficial effects on
cardiovascular risk by improving lean and fat body mass, total and LDL cholesterol levels,
and diastolic blood pressure (7). Besides, GH replacement also induces improvement in
cardiovascular markers (8), and cardiac performance (9). In small cohorts of GHD adults,
beneficial effects of GH replacement for 6-24 mos have also been reported on surrogate
parameters of atherosclerosis, such as intima-media thickness (IMT) at major arteries
(10-13), while 6 months of GH deprivation is associated with an impairment of the
cardiovascular risk profile (12). In a consistent series of men and women with
hypopituitarism we reported, however, that two years of GH replacement is not adequate to
normalize IMT levels at common carotid arteries (13).
To give further insights on the likelihood of reversal of early atherosclerosis in severe GHD
patients after prolonged GH replacement, we designed this 5-yr prospective, controlled study.
Only men aged ≤50 yrs and with severe GHD were enrolled to avoid gender and aging
interference (13). Main outcome measure was IMT at common carotid arteries; secondary measure
was prevalence of insulin-resistance syndrome according with the American College of
Endocrinology (14).