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. 1991 Oct;32(4):417–422. doi: 10.1111/j.1365-2125.1991.tb03924.x

Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia.

R H Jay 1, R H Sturley 1, C Stirling 1, H H McGarrigle 1, M Katz 1, J P Reckless 1, D J Betteridge 1
PMCID: PMC1368599  PMID: 1958433

Abstract

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.

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Selected References

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  1. Adamopoulos D., Lawrence D. M., Vassilopoulos P., Kapolla N., Kontogeorgos L., McGarrigle H. H. Hormone levels in the reproductive system of normospermic men and patients with oligospermia and varicocele. J Clin Endocrinol Metab. 1984 Sep;59(3):447–452. doi: 10.1210/jcem-59-3-447. [DOI] [PubMed] [Google Scholar]
  2. Borkowski A., Delcroix C., Levin S. Metabolism of adrenal cholesterol in man. I. In vivo studies. J Clin Invest. 1972 Jul;51(7):1664–1678. doi: 10.1172/JCI106968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borkowski A., Delcroix C., Levin S. Metabolism of adrenal cholesterol in man. II. In vitro studies including a comparison of adrenal cholesterol synthesis with the synthesis of the clucocorticosteroid hormones. J Clin Invest. 1972 Jul;51(7):1679–1687. doi: 10.1172/JCI106969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown M. S., Kovanen P. T., Goldstein J. L. Receptor-mediated uptake of lipoprotein-cholesterol and its utilization for steroid synthesis in the adrenal cortex. Recent Prog Horm Res. 1979;35:215–257. doi: 10.1016/b978-0-12-571135-7.50009-6. [DOI] [PubMed] [Google Scholar]
  5. Carr B. R., Simpson E. R. Lipoprotein utilization and cholesterol synthesis by the human fetal adrenal gland. Endocr Rev. 1981 Summer;2(3):306–326. doi: 10.1210/edrv-2-3-306. [DOI] [PubMed] [Google Scholar]
  6. Darne F. J., McGarrigle H. H., Lachelin G. C. Diurnal variation of plasma and saliva oestrogen, progesterone, cortisol and plasma dehydroepiandrosterone sulphate in late pregnancy. Eur J Obstet Gynecol Reprod Biol. 1989 Aug;32(2):57–66. doi: 10.1016/0028-2243(89)90184-6. [DOI] [PubMed] [Google Scholar]
  7. FORD R. V. The effect of MER-29, a cholesterol synthesis inhibitor, on adrenal function, blood clotting mechanisms, and serum lipids, before and after simulated stress in man. Prog Cardiovasc Dis. 1960 May;2:548–552. doi: 10.1016/s0033-0620(60)80030-8. [DOI] [PubMed] [Google Scholar]
  8. Farnsworth W. H., Hoeg J. M., Maher M., Brittain E. H., Sherins R. J., Brewer H. B., Jr Testicular function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin) or neomycin. J Clin Endocrinol Metab. 1987 Sep;65(3):546–550. doi: 10.1210/jcem-65-3-546. [DOI] [PubMed] [Google Scholar]
  9. Fojo S. S., Hoegg J. M., Lackner K. J., Anchors J. M., Bailey K. R., Brewer H. B., Jr Adrenocortical function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin). Horm Metab Res. 1987 Dec;19(12):648–652. doi: 10.1055/s-2007-1011900. [DOI] [PubMed] [Google Scholar]
  10. Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
  11. Germershausen J. I., Hunt V. M., Bostedor R. G., Bailey P. J., Karkas J. D., Alberts A. W. Tissue selectivity of the cholesterol-lowering agents lovastatin, simvastatin and pravastatin in rats in vivo. Biochem Biophys Res Commun. 1989 Feb 15;158(3):667–675. doi: 10.1016/0006-291x(89)92773-3. [DOI] [PubMed] [Google Scholar]
  12. Grundy S. M., Bilheimer D. W. Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase by mevinolin in familial hypercholesterolemia heterozygotes: effects on cholesterol balance. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2538–2542. doi: 10.1073/pnas.81.8.2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Grundy S. M. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med. 1988 Jul 7;319(1):24–33. doi: 10.1056/NEJM198807073190105. [DOI] [PubMed] [Google Scholar]
  14. Illingworth D. R., Alam N. A., Lindsey S. Adrenocortical response to adrenocorticotropin in heterozygous familial hypercholesterolemia. J Clin Endocrinol Metab. 1984 Jan;58(1):206–211. doi: 10.1210/jcem-58-1-206. [DOI] [PubMed] [Google Scholar]
  15. Illingworth D. R., Corbin D. The influence of mevinolin on the adrenal cortical response to corticotropin in heterozygous familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6291–6294. doi: 10.1073/pnas.82.18.6291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Illingworth D. R., Kenny T. A., Orwoll E. S. Adrenal function in heterozygous and homozygous hypobetalipoproteinemia. J Clin Endocrinol Metab. 1982 Jan;54(1):27–33. doi: 10.1210/jcem-54-1-27. [DOI] [PubMed] [Google Scholar]
  17. Illingworth D. R., Lees A. M., Lees R. S. Adrenal cortical function in homozygous familial hypercholesterolemia. Metabolism. 1983 Nov;32(11):1045–1052. doi: 10.1016/0026-0495(83)90075-6. [DOI] [PubMed] [Google Scholar]
  18. Koga T., Shimada Y., Kuroda M., Tsujita Y., Hasegawa K., Yamazaki M. Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Biochim Biophys Acta. 1990 Jul 16;1045(2):115–120. doi: 10.1016/0005-2760(90)90139-o. [DOI] [PubMed] [Google Scholar]
  19. Laue L., Hoeg J. M., Barnes K., Loriaux D. L., Chrousos G. P. The effect of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway. J Clin Endocrinol Metab. 1987 Mar;64(3):531–535. doi: 10.1210/jcem-64-3-531. [DOI] [PubMed] [Google Scholar]
  20. Mol M. J., Stalenhoef A. F., Stuyt P. M., Hermus A. R., Demacker P. N., Van 'T Laar A. Effects of inhibition of cholesterol synthesis by simvastatin on the production of adrenocortical steroid hormones and ACTH. Clin Endocrinol (Oxf) 1989 Dec;31(6):679–689. doi: 10.1111/j.1365-2265.1989.tb01293.x. [DOI] [PubMed] [Google Scholar]
  21. Mosley S. T., Kalinowski S. S., Schafer B. L., Tanaka R. D. Tissue-selective acute effects of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase on cholesterol biosynthesis in lens. J Lipid Res. 1989 Sep;30(9):1411–1420. [PubMed] [Google Scholar]
  22. Reihnér E., Rudling M., Ståhlberg D., Berglund L., Ewerth S., Björkhem I., Einarsson K., Angelin B. Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol. N Engl J Med. 1990 Jul 26;323(4):224–228. doi: 10.1056/NEJM199007263230403. [DOI] [PubMed] [Google Scholar]
  23. Thompson G. R., Ford J., Jenkinson M., Trayner I. Efficacy of mevinolin as adjuvant therapy for refractory familial hypercholesterolaemia. Q J Med. 1986 Aug;60(232):803–811. [PubMed] [Google Scholar]
  24. Tobert J. A., Bell G. D., Birtwell J., James I., Kukovetz W. R., Pryor J. S., Buntinx A., Holmes I. B., Chao Y. S., Bolognese J. A. Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers. J Clin Invest. 1982 Apr;69(4):913–919. doi: 10.1172/JCI110530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsujita Y., Kuroda M., Shimada Y., Tanzawa K., Arai M., Kaneko I., Tanaka M., Masuda H., Tarumi C., Watanabe Y. CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta. 1986 Jun 11;877(1):50–60. doi: 10.1016/0005-2760(86)90117-7. [DOI] [PubMed] [Google Scholar]
  26. Uauy R., Vega G. L., Grundy S. M., Bilheimer D. M. Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentrations or turnover. J Pediatr. 1988 Aug;113(2):387–392. doi: 10.1016/s0022-3476(88)80289-0. [DOI] [PubMed] [Google Scholar]
  27. Warnick G. R., Albers J. J. A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res. 1978 Jan;19(1):65–76. [PubMed] [Google Scholar]

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