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EFFECTS OF INHIBITION OF CHOLESTEROL SYNTHESIS BY SIMVASTATIN ON THE PRODUCTION OF ADRENOCORTICAL STEROID HORMONES AND ACTH
Author(s) -
MOL M. J. T. M.,
STALENHOEF A. F. H.,
STUYT P. M. J.,
HERMUS A. R. M. M.,
DEMACKER P. N. M.,
'TLAAR A.
Publication year - 1989
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1989.tb01293.x
Subject(s) - medicine , endocrinology , simvastatin , adrenocorticotropic hormone , cholesterol , hormone , basal (medicine) , chemistry , insulin
SUMMARY 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.