Top

Published in:

01-02-2011

Lipid Effects of Endocrine Medications

Authors: Dan V. Mihailescu, Avni Vora, Theodore Mazzone

Published in: Current Atherosclerosis Reports | Issue 1/2011

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.

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.CrossRefPubMed

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.CrossRefPubMed

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.

Mazzone T, Foster D, Chait A: In vivo stimulation of low-density lipoprotein degradation by insulin. Diabetes 1984, 33:333–338.CrossRefPubMed

Mason RL, Hunt HM, Hurxthal LM: Blood cholesterol values in hyperthyroidism and hypothyroidism: their significance. N Engl J Med 1930, 203:1273–1278.CrossRef

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.CrossRefPubMed

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.CrossRefPubMed

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.PubMed

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.CrossRefPubMed

10.

Yen PM: Physiological and molecular basis of thyroid hormone action. Physiol Rev 2001, 81:1097–1142.PubMed

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.CrossRefPubMed

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. CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.PubMed

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.PubMed

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.CrossRefPubMed

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).

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.CrossRefPubMed

21.

Makinen JI, Perheentupa A, Irjala K, et al.: Endogenous testosterone and serum lipids in middle-aged men. Atherosclerosis 2008, 197:688–693.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

24.

Thompson PD, Cullinane EM, Sady SP, et al.: Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA 1989, 261:1165–1168.CrossRefPubMed

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. CrossRefPubMed

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. CrossRefPubMed

27.

De Boer H, Blok GJ, Voerman HJ, et al.: Serum lipid levels in growth hormone-deficient men. Metabolism 1994, 43:199–203.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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. CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

35.

Ettinger WH, Klineffelter HF, Kwiterowich PO: Effect of short-term, low dose glucocorticoids on plasma lipoprotein lipids. Atherosclerosis 1987, 63:167–172.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

40.

Lam NT, Kieffer TJ: The multifaceted potential of glucagon-like peptide-1 as a therapeutic agent. Minerva Endocrinol 2002, 27:79–93.PubMed

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.CrossRefPubMed

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. PubMed

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. CrossRefPubMed

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.CrossRefPubMed

45.

Karpe F, Steiner G, Uffelman K, et.al.: Postprandial lipoproteins and progression of coronary atherosclerosis. Atherosclerosis 1994, 106:83–97.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

48.

Reynolds K, Goldberg RB: Thiazolidinediones: beyond glycemic control. Treat Endocrinol 2006, 5:25–36.CrossRefPubMed

49.

Betteridge DJ: Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab 2007, 9:640–647.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

Title: Lipid Effects of Endocrine Medications
Authors: Dan V. Mihailescu
Avni Vora
Theodore Mazzone
Publication date: 01-02-2011
Publisher: Current Science Inc.
Published in: Current Atherosclerosis Reports / Issue 1/2011
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-010-0146-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

A Potential Novel Therapeutic Addition to Statin Therapy for Dyslipidemia

Statins in Combinations: From ARBITER-6 HALTS to ACCORD—What Works?

Statin Therapy in Metabolic Syndrome and Hypertension Post-JUPITER: What is the Value of CRP?

Statin Rebound or Withdrawal Syndrome: Does It Exist?

Are Cardiovascular Benefits in Statin Lipid Effects Dependent on Baseline Lipid Levels?

Combination Lipid Therapy in Type 2 Diabetes

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials