Effect of 5 Years of GH Replacement on Atherosclerosis

• Status: Completed
• Trial end date: 2006-12-01
• Target enrollment: 0
• Participant gender: Male

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).

• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Federico II University
• Treatments: Hormones

Criteria

Inclusion Criteria:

• male gender

• age <50 yrs to limit the effect of aging;

• body mass index <30 Kg/m2;

• no familial or personal history of cardiovascular diseases;

• no concomitant treatment with drugs known to interfere with glucose or lipid metabolism or to influence blood pressure at the time of study entry;

• no previous GH treatment

Exclusion Criteria:

• female gender

• age >50 yrs;

• body mass index ≥30;

• familial or personal history of cardiovascular diseases;

• previous and present treatments with drugs known to interfere with glucose or lipid metabolism or to influence blood pressure;

• previous GH treatment in adult age

• GHD of childhood onset

• GHD due to previous Cushing's disease