Current Atherosclerosis Reports

, Volume 13, Issue 1, pp 88–94

Lipid Effects of Endocrine Medications

Article

Abstract

Various alterations of lipid homeostasis have a significant role in the pathophysiology of the artherosclerotic process. The effects of usual lipid-lowering agents such as statins, fibrates, or niacin are well known, but other endocrine therapeutic agents could also affect the blood levels of various lipoproteins and, in turn, influence atheroma formation. In this review, we attempt to summarize the effect of several hormonal and non-hormonal endocrine agents on lipid metabolism, including insulin, thyroid hormone, sex hormones, glucocorticoids, growth hormone, and several anti-diabetic agents.

Keywords

Lipids Cardiovascular Cholesterol LDL HDL Insulin Growth hormone Thyroid hormone Testosterone Estrogen 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Farese RV Jr, Yost TJ, Eckel RH, et al.: Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans. Metabolism 1991, 40:214–216.CrossRefPubMedGoogle Scholar
  2. 2.
    Garvey WT, Kwon S, Zheng D, et al.: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 2003, 52:453–462.CrossRefPubMedGoogle Scholar
  3. 3.
    Feingold KR, Grunfeld C, Pang M, et al.: LDL subclass phenotypes and triglyceride metabolism in non-insulin-dependent diabetes. Arterioscler Thromb Vasc Biol 1992, 12:1496–1502.Google Scholar
  4. 4.
    Mazzone T, Foster D, Chait A: In vivo stimulation of low-density lipoprotein degradation by insulin. Diabetes 1984, 33:333–338.CrossRefPubMedGoogle Scholar
  5. 5.
    Mason RL, Hunt HM, Hurxthal LM: Blood cholesterol values in hyperthyroidism and hypothyroidism: their significance. N Engl J Med 1930, 203:1273–1278.CrossRefGoogle Scholar
  6. 6.
    Thompson GR, Soutar AK, Spengel FA, et al.: Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci U S A 1981, 78:2591–2595.CrossRefPubMedGoogle Scholar
  7. 7.
    Pykalisto O, Goldberg AP, Brunzell JD: Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism. J Clin Endocrinol Metab 1976, 43:591–600.CrossRefPubMedGoogle Scholar
  8. 8.
    O’Brien T, Dinneen SF, O’Brien PC, et al.: Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993, 68:860–866.PubMedGoogle Scholar
  9. 9.
    Ito M, Arishima T, Kudo T, et al.: Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients. J Clin Endocrinol Metab 2007, 92:608–611.CrossRefPubMedGoogle Scholar
  10. 10.
    Yen PM: Physiological and molecular basis of thyroid hormone action. Physiol Rev 2001, 81:1097–1142.PubMedGoogle Scholar
  11. 11.
    Johansson L, Rudling M, Scanlan TS, et al.: Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice. Proc Natl Acad Sci U S A 2005, 102:10297–10302.CrossRefPubMedGoogle Scholar
  12. 12.
    • Ladenson P, Kristensen P, Ridgway EC, et al.: Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010, 362:906–916. Eprotirome, a thyroid hormone analogue, has been shown in this randomized, prospective, placebo-controlled study to significantly decrease the levels of atherogenic lipoproteins in patients already receiving statin therapy. CrossRefPubMedGoogle Scholar
  13. 13.
    Darling GM, Johns JA, McCloud PI, et al.: Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997, 337:595–601.CrossRefPubMedGoogle Scholar
  14. 14.
    Hulley S, Grady D, Bush T, et al.: Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998, 280:605–613.CrossRefPubMedGoogle Scholar
  15. 15.
    Rossouw JE, Anderson GL, Prentice RL, et al.: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002, 288:321–333.CrossRefPubMedGoogle Scholar
  16. 16.
    Kim CJ, Jang HC, Cho DH, et al.: Effects of hormone replacement therapy on lipoprotein(a) and lipids in postmenopausal women. Arterioscler Thromb 1994, 14:275–281.PubMedGoogle Scholar
  17. 17.
    Ottosson UB, Johansson BG, von Schoultz B: Subfractions of high-density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone. Am J Obstet Gynecol 1985, 151:746–750.PubMedGoogle Scholar
  18. 18.
    Clarke SC, Kelleher J, Lloyd-Jones H, et al.: A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. BJOG 2002, 109:1056–1062.CrossRefPubMedGoogle Scholar
  19. 19.
    Haring R, Baumeister S, Volzke H, et al.: Prospective association of low total testosterone concentrations with an adverse lipid profile and increased incident dyslipidemia. Eur J Cardiovasc Prev Rehab 2010 (in press).Google Scholar
  20. 20.
    Haffner SM, Mykkanen L, Valdez RA, et al.: Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab 1993, 77:1610–1615.CrossRefPubMedGoogle Scholar
  21. 21.
    Makinen JI, Perheentupa A, Irjala K, et al.: Endogenous testosterone and serum lipids in middle-aged men. Atherosclerosis 2008, 197:688–693.CrossRefPubMedGoogle Scholar
  22. 22.
    Zitzmann M, Nieschlag E: Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab 2007, 92:3844–3853.CrossRefPubMedGoogle Scholar
  23. 23.
    Zgliczynski S, Ossowski M, Slowinska-Srzednicka J, et al.: Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis 1996, 121:35–43.CrossRefPubMedGoogle Scholar
  24. 24.
    Thompson PD, Cullinane EM, Sady SP, et al.: Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA 1989, 261:1165–1168.CrossRefPubMedGoogle Scholar
  25. 25.
    • Basaria S, Coviello A, Travison T, et al.: Adverse Events Associated with Testosterone Administration. N Engl J Med 2010, 363:109–122. Testosterone administration in older men with limited mobility has been associated with an increased risk of cardiovascular adverse events. CrossRefPubMedGoogle Scholar
  26. 26.
    •• Fernandez-Balsells NM, Murad MH, Lane M, et al.: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010, 95:2560–2575. This meta-analysis included 51 studies and concluded that the adverse effects of testosterone therapy include a decrease in HDL cholesterol with no significant effect on cardiovascular outcomes or mortality. CrossRefPubMedGoogle Scholar
  27. 27.
    De Boer H, Blok GJ, Voerman HJ, et al.: Serum lipid levels in growth hormone-deficient men. Metabolism 1994, 43:199–203.CrossRefPubMedGoogle Scholar
  28. 28.
    Barreto-Filho JA, Alcantara MR, Salvatori R, et al.: Familial isolated growth hormone deficiency is associated with increased systolic blood pressure, central obesity, and dyslipidemia. J Clin Endocrinol Metab 2002, 87:2018–2023.CrossRefPubMedGoogle Scholar
  29. 29.
    Weaver JU, Monson JP, Noonan K, et al.: The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. J Clin Endocrinol Metab 1995, 80:153–159.CrossRefPubMedGoogle Scholar
  30. 30.
    Beauregard C, Utz AL, Schaub AE, et al.: Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 2008, 93:2063–2071.CrossRefPubMedGoogle Scholar
  31. 31.
    • Miller K, Wexler T, Fazeli P, et al.: Growth hormone deficiency after treatment of acromegaly: a randomized, placebo-controlled study of growth hormone replacement. J Clin Endocrinol Metab 2010, 95:567–577. Growth hormone replacement therapy in deficient patients post-treatment for acromegaly has been associated with an increased fat-free mass, and decreased visceral adipose tissue and hsCRP, but no effects on other cardiovascular markers. CrossRefPubMedGoogle Scholar
  32. 32.
    Borson-Chazot F, Serusclat A, Kalfallah Y, et al.: Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab 1999, 84:1329–1333.CrossRefPubMedGoogle Scholar
  33. 33.
    Colao A, Di Somma C, Spiezia S, et al.: Growth hormone treatment on atherosclerosis: results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. J Clin Endocrinol Metab 2008, 93:3416–3424.CrossRefPubMedGoogle Scholar
  34. 34.
    Ebden P, McNally P, Samanta A, et al.: The effects of high dose inhaled beclomethasone dipropionate on glucose and lipid profiles in normal and diet controlled diabetic subjects. Respir Med 1989, 83:289–291.CrossRefPubMedGoogle Scholar
  35. 35.
    Ettinger WH, Klineffelter HF, Kwiterowich PO: Effect of short-term, low dose glucocorticoids on plasma lipoprotein lipids. Atherosclerosis 1987, 63:167–172.CrossRefPubMedGoogle Scholar
  36. 36.
    Choi HK, Seeger JD: Glucocorticoid use and serum lipid levels in US adults: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 2005, 53:528–535.CrossRefPubMedGoogle Scholar
  37. 37.
    Souverein PC, Berard A, Van Staa TP, et al.: Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case-control study. Heart 2004, 90:859–865.CrossRefPubMedGoogle Scholar
  38. 38.
    Toft-Nielsen MB, Madsbad S, Holst JJ: Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes. J Clin Endocrinol Metab 2001, 86:3853–3860.CrossRefPubMedGoogle Scholar
  39. 39.
    Soltani N, Kumar M, Glinka Y, et al.: In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes. Gene Ther 2007, 14:981–988.CrossRefPubMedGoogle Scholar
  40. 40.
    Lam NT, Kieffer TJ: The multifaceted potential of glucagon-like peptide-1 as a therapeutic agent. Minerva Endocrinol 2002, 27:79–93.PubMedGoogle Scholar
  41. 41.
    Blonde L, Klein J, Han J. et al. Interim analysis of the effects of exenatide treatment on A1C, weight and cardiovascular risk factors over 82 weeks in 314 overweight patients with type 2 diabetes. Diabetes Obes Metab 2006, 8:436–447.CrossRefPubMedGoogle Scholar
  42. 42.
    • Klonoff DC, Buse JB, Nielsen LL, et al.: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008, 24:275–286. This placebo-controlled trial demonstrated that extended use of exanetide could improve total cholesterol, triglyceride, HDL, and LDL levels. PubMedGoogle Scholar
  43. 43.
    •• Schwartz EA, Koska J, Mullin MP, et al.: Exenatide suppresses postprandial elevations in lipids and lipoproteins in individuals with impaired glucose tolerance and recent onset type2 diabetes mellitus. Atherosclerosis 2010, 212:217–222. This randomized, double-blinded, placebo-controlled crossover study showed that exenatide markedly reduced post-prandial concentrations of pro-atherogenic lipids, specifically triglycerides, apolipoproteins B-48 and CIII, and RLP. CrossRefPubMedGoogle Scholar
  44. 44.
    Eberly LE, Stamler J, Neaton JD: Relation of triglyceride levels, fasting and nonfasting, to fatal and nonfatal coronary heart disease. Arch Intern Med 2003, 163:1077–1083.CrossRefPubMedGoogle Scholar
  45. 45.
    Karpe F, Steiner G, Uffelman K, et.al.: Postprandial lipoproteins and progression of coronary atherosclerosis. Atherosclerosis 1994, 106:83–97.CrossRefPubMedGoogle Scholar
  46. 46.
    Scheffer PG, Teerlink T, Dekker JM, et al.: Increased plasma apolipoprotein C-III concentration independently predicts cardiovascular mortality: the Hoorn study. Clin Chem 2008, 54:1325–1230.CrossRefPubMedGoogle Scholar
  47. 47.
    Pirro M, Mauriège P, Tchernof A, et al.: Plasma free fatty acid levels and the risk of ischemic heart disease in men: prospective results from the Québec Cardiovascular Study. Atherosclerosis 2002, 160:377–384.CrossRefPubMedGoogle Scholar
  48. 48.
    Reynolds K, Goldberg RB: Thiazolidinediones: beyond glycemic control. Treat Endocrinol 2006, 5:25–36.CrossRefPubMedGoogle Scholar
  49. 49.
    Betteridge DJ: Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab 2007, 9:640–647.CrossRefPubMedGoogle Scholar
  50. 50.
    Dormandy JA, Charbonnel B, Eckland DJ, et al.: Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005, 366:1279–1289.CrossRefPubMedGoogle Scholar
  51. 51.
    Mazzone T. Meyer P, Feinstein S et al.: Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006, 296:2572-2581.CrossRefPubMedGoogle Scholar
  52. 52.
    Davidson M, Meyer PM, Haffner S, et al.: Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation 2008, 117:2123–2130.CrossRefPubMedGoogle Scholar
  53. 53.
    Goldberg RB, Kendall DM, Deeg MA, et al.: A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005, 28:1547–1554.CrossRefPubMedGoogle Scholar
  54. 54.
    Charbonnel B, Karasik A, Liu J, et al. : Efficacy and safety of the dipeptidylpeptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006, 29:2638–2643.CrossRefPubMedGoogle Scholar
  55. 55.
    Matikainen N, Mänttäri S, Schweizer A, et al.: Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes. Diabetologia 2006, 49:2049–2057.CrossRefPubMedGoogle Scholar
  56. 56.
    Wulffelé MG, Kooy A, de Zeeuw D, et al.: The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med 2004, 256:1–14.CrossRefPubMedGoogle Scholar
  57. 57.
    Holman RR, Paul SK, Bethel MA et al.: 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008, 359:1577–1589.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Dan V. Mihailescu
    • 1
  • Avni Vora
    • 1
  • Theodore Mazzone
    • 2
  1. 1.Department of MedicineUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Departments of Medicine, Pharmacology, and Kinesiology and NutritionUniversity of Illinois at ChicagoChicagoUSA

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