Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy

OBJECTIVE Adult onset GH deficiency (GHD) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)-cholesterol. Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor (statin) therapy. We have examined this possibility during prospective follow-up of adult onset hypopituitary patients enrolled in KIMS (Pfizer International Metabolic Database), a pharmacoepidemiological study of GH replacement in adult hypopituitary patients. DESIGN Lipoprotein profiles were measured centrally at baseline and after 12 months GH replacement therapy. PATIENTS Sixty-one hypopituitary patients (30 male, 31 female) on maintenance statin therapy (mean 2.5 +/- 2.7 SD years before GH) (statin group - SG) and 1247 (608 male, 639 female) patients not on hypolipidaemic therapy (nonstatin group - NSG) were studied. All patients were naïve or had not received GH replacement during the 6 months prior to study. Patients who developed diabetes mellitus during the first year of GH therapy or in the subsequent year and those with childhood onset GHD were excluded from this analysis. An established diagnosis of diabetes mellitus was present in 18% SG and 4.4% NSG at baseline. MEASUREMENTS Serum concentrations of total, high density lipoprotein (HDL)-cholesterol, triglycerides and IGF-I were measured centrally in all patients and LDL-cholesterol was estimated using Friedewald's formula. RESULTS The relative frequency of various statin use was simvastatin 52% (15.8 +/- 8.1 mg, mean +/- SD), atorvastatin 30% (14.4 +/- 7.8 mg), pravastatin 9.8% (31.6 mg +/- 13.9 mg), lovastatin 6.6% (17.5 +/- 5 mg) and fluvastatin 1.6% (40 mg). Baseline serum total and LDL-cholesterol (mean +/- SD) were 5.2 +/- 1.4 and 3.1 +/- 1.3 mmol/l in SG and 5.8 +/- 1.2 and 3.7 +/- 1.0 mmol/l in NSG, respectively (P < 0.0001, SG vs. NSG). After 12 months GH replacement (SG: 0.32 +/- 0.17 mg/day; NSG: 0.38 +/- 0.1 mg/day) serum total and LDL-cholesterol decreased by a mean (+/-SD) of 0.48 (+/- 1.25) mmol/l (P < 0.0004) and 0.53 (+/- 1.08) mmol/l (P < 0.0001) in SG and by 0.30 (+/- 0.89) mmol/l (P < 0.0001) and 0.28 (+/- 0.80) mmol/l (P < 0.0001) in NSG, respectively. There were no significant changes in HDL-cholesterol or triglycerides in either group (SG vs. NSG: NS). A relationship between LDL-cholesterol at baseline and the decrease in LDL-cholesterol after 12 months GH was evident in both groups (SG: R = -0.54, P < 0.001; NSG: R = -0.4, P < 0.001) and a similar relationship for cholesterol was observed. CONCLUSIONS These data indicate that GH replacement exerts additional beneficial effects on lipoprotein profiles in patients on maintenance statin therapy, confirming that the effects of these interventions are complementary rather than exclusive.