Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia.
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.
Jay
R H
RH
Department of Medicine, University College and Middlesex School of Medicine, Rayne Institute, London.
Sturley
R H
RH
Stirling
C
C
McGarrigle
H H
HH
Katz
M
M
Reckless
J P
JP
Betteridge
D J
DJ
D000311:Adrenal Glands / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis; D006065:Gonadotropins, Pituitary / Q000097:blood; D006066:Gonads / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013256:Steroids / Q000096:biosynthesis*
D012739:Gonadal Steroid Hormones; D006065:Gonadotropins, Pituitary; D012738:Sex Hormone-Binding Globulin; D013256:Steroids; D002792:Cholestyramine Resin; D017035:Pravastatin; D006854:Hydrocortisone