EFFECTS OF INHIBITION OF CHOLESTEROL SYNTHESIS BY SIMVASTATIN ON THE PRODUCTION OF ADRENOCORTICAL STEROID HORMONES AND ACTH

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Abstract
Simvastatin, a derivative of lovastatin, is a potent inhibitor of cholesterol biosynthesis and may interfere with steroid hormone production, for which cholesterol is required. In a single‐blind, placebo‐controlled study, 24 patients with severe primary hypercholesterolaemia (mean serum cholesterol ± SD = 10.74 ± 1.59 mmol/l) were treated with simvastatin 40 mg per day for 8 weeks. Before and after treatment, the following parameters were evaluated: basal levels of ACTH, cortisol, androstenedione, dehydroepiandrosterone and 17‐hydroxyprogesterone; urinary excretion of free cortisol; the cortisol response after short‐term infusion of ACTH; the ACTH and cortisol response during insulin‐induced hypoglycaemia. Total serum cholesterol decreased by 35.0 ± 8.1% (P < 0.001) and low‐density lipoprotein (LDL) cholesterol by 39.8 ± 9.8% (P < 0.001); high‐density lipoprotein (HDL) increased by 9.2 ± 11.1% (P < 0.001). Basal levels of ACTH were higher after simvastatin (2.9 ± 1.9 pmol/1 vs 4.1 ± 2.9 pmol/l; P < 0.05) whereas basal levels of steroid hormones were not significantly changed. The excretion of free cortisol was unaltered. The peak cortisol after ACTH infusion was lower after treatment (0.87 ± 0.23 μmol/l vs 0.78 ± 0.10 μmol/l; P < 0.05), but was unaltered during insulin‐induced hypoglycaemia. We conclude that simvastatin lowers serum cholesterol without clinically relevant effects on the adrenocortical steroid hormone secretion and the hypothalamic‐pituitary‐adrenal axis.