EFFECTS OF PRAVASTATIN AND CHOLESTYRAMINE ON GONADAL AND ADRENAL-STEROID PRODUCTION IN FAMILIAL HYPERCHOLESTEROLEMIA

1 Adrenal and gonadal steroids are derived from cholesterol, which may be derived from plasma lipoproteins or de novo synthesis. 2 Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme in cholesterol synthesis, may therefore affect steroidogenesis when used as lipid-lowering agents in hypercholesterolaemia. 3 We have assessed gonadal and adrenal function in subjects with heterozygous familial hypercholesterolaemia (FH) before and after 12 weeks treatment with pravastatin, an HMG CoA reductase inhibitor, or cholestyramine as a control in maximal recommended doses. 4 No changes in measured plasma cortisol responses to tetracosactrin injection were seen in 11 patients on cholestyramine or 12 on pravastatin. 5 No changes were seen in testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulphate, oestradiol or 17-alpha-hydroxyprogesterone. 6 Gonadotrophin levels were unaffected in 10 male subjects on cholestyramine and 7 on pravastatin. 7 Measurements on a subset of subjects continuing to 24 weeks treatment also showed no changes. 8 No adverse effect on adrenal or gonadal function could be demonstrated in patients with familial hypercholesterolaemia on maximal recommended doses of pravastatin.