OBJECTIVES: Many reports demonstrate improvements in cardiovascular risk factors during GH replacement (rhGH) in adult GH deficiency (GHD). However, it remains to be determined to what extent these changes translate into a reduction of increased cardiovascular morbidity and mortality. The aim of this study was to evaluate the effects of long-term rhGH replacement on the prevalence of the metabolic syndrome (MS). Design, settings, main outcome measures: The MS was scored by the National Cholesterol Education Program-Adult Treatment Panel III definition in 50 consecutive GHD patients (45 +/- 9 years of age), before and after 2 and 5 years of rhGH replacement, and the data of untreated patients were compared with the general population using data from a Dutch population-based study (n=1062, 44 +/- 8 years of age). RESULTS: Hypertriglyceridaemia (46.0 vs 18.5%, P<0.0001), hypertension (66.0 vs 35.5%, P<0.0001) and abdominal obesity (38.0 vs 23.4%, P=0.0178) were more prevalent in untreated patients when compared with controls, resulting in a higher prevalence of the MS in patients (38.0 vs 15.7%, P<0.0001). During rhGH replacement at a mean dose of 0.5 +/- 0.2 mg/day resulting in IGF-I concentrations in the normal age-adjusted reference range, mean high-density lipoprotein cholesterol level increased compared with baseline (P<0.001). However, the prevalence of (components of) the MS did not change after 2 or 5 years of treatment with rhGH. CONCLUSION: In this study, the prevalence of the MS in patients with GHD is increased compared with healthy controls, irrespective of rhGH replacement.