European Journal of Epidemiology

, Volume 24, Issue 6, pp 289–295 | Cite as

Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromsø study

  • T. Vikan
  • S. H. Johnsen
  • H. Schirmer
  • I. Njølstad
  • J. Svartberg
Cardiovascular Disease

Abstract

The role of testosterone in the development of cardiovascular disease is controversial. Recent observational studies, however, suggest a protective role of normal endogenous testosterone levels in the development of atherosclerosis. In a cohort from the Tromsø study, 1,101 men had both hormone-levels measured and the right carotid artery examined by ultrasound in 1994 and 2001. We studied the prospective association between sex hormone-levels and progression of carotid intima-media thickness (IMT) and plaque area from 1994 to 2001. We also performed a cross-sectional study of 2,290 men from the population in 2001. The data were analysed by univariate correlations, analyses of covariance and multiple linear regression analyses. In the cross-sectional study, we found an inverse association between testosterone levels and total carotid plaque area (P < 0.05), after adjusting for age, systolic blood pressure, smoking and use of lipid-lowering drugs. We found no prospective associations between sex hormone-levels and change in plaque area or IMT from 1994 to 2001. The lack of prospective associations in our study may be due to increased use of anti-hypertensive and lipid-lowering drugs from 1994 baseline to follow-up.

Keywords

Prospective Cross-sectional Intima-media thickness Plaque area Atherosclerosis Testosterone 

Abbreviations

BMI

Body mass index

CCA

Common carotid artery

HDL

High density lipid cholesterol

IMT

Intima media thickness

SHBG

Sex hormone-binding globulin

References

  1. 1.
    Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev. 2003;24:313–40. doi:10.1210/er.2003-0005.PubMedCrossRefGoogle Scholar
  2. 2.
    Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26:833–76. doi:10.1210/er.2004-0013.PubMedCrossRefGoogle Scholar
  3. 3.
    Svartberg J, Von Mühlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø study. Eur J Endocrinol. 2004;150:65–71. doi:10.1530/eje.0.1500065.PubMedCrossRefGoogle Scholar
  4. 4.
    Khaw KT, Barrett-Connor E. Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertens. 1988;6:329–32. doi:10.1097/00004872-198804000-00010.PubMedCrossRefGoogle Scholar
  5. 5.
    Agledahl I, Skjærpe PA, Hansen JB, Svartberg J. Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: the Tromsø study. Nutr Metab Cardiovasc Dis. 2008;18:256–62. doi:10.1016/j.numecd.2007.01.014.PubMedCrossRefGoogle Scholar
  6. 6.
    Svartberg J, von Mühlen D, Sundsfjord J, Jorde R. Waist circumference and testosterone levels in community dwelling men. The Tromsø study. Eur J Epidemiol. 2004;19:657–63. doi:10.1023/B:EJEP.0000036809.30558.8f.PubMedCrossRefGoogle Scholar
  7. 7.
    Svartberg J, Jenssen T, Sundsfjord J, Jorde R. The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. The Tromsø study. Diabetes Metab. 2004;30:29–34. doi:10.1016/S1262-3636(07)70086-1.PubMedCrossRefGoogle Scholar
  8. 8.
    Haffner SM, Mykkanen L, Valdez RA, Katz MS. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993;77:1610–5. doi:10.1210/jc.77.6.1610.PubMedCrossRefGoogle Scholar
  9. 9.
    Van Pottelbergh I, Braeckman L, De Bacquer D, De Backer G, Kaufman JM. Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men. Atherosclerosis. 2003;166:95–102. doi:10.1016/S0021-9150(02)00308-8.PubMedCrossRefGoogle Scholar
  10. 10.
    Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997;96:1432–7.PubMedGoogle Scholar
  11. 11.
    Ebrahim S, Papacosta O, Whincup P, et al. Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British regional heart study. Stroke. 1999;30:841–50.PubMedGoogle Scholar
  12. 12.
    Brook RD, Bard RL, Patel S, et al. A negative carotid plaque area test is superior to other noninvasive atherosclerosis studies for reducing the likelihood of having underlying significant coronary artery disease. Arterioscler Thromb Vasc Biol. 2006;26:656–62. doi:10.1161/01.ATV.0000200079.18690.60.PubMedCrossRefGoogle Scholar
  13. 13.
    Johnsen SH, Mathiesen EB, Joakimsen O, et al. Carotid atherosclerosis is a stronger predictor of myocardial infarction in women than in men: a 6-Year follow-up study of 6226 persons: the Tromsø study. Stroke. 2007;38:2873–80. doi:10.1161/STROKEAHA.107.487264.PubMedCrossRefGoogle Scholar
  14. 14.
    Svartberg J, von Mühlen D, Mathiesen E, Joakimsen O, Bonaa KH, Stensland-Bugge E. Low testosterone levels are associated with carotid atherosclerosis in men. J Intern Med. 2006;259:576–82. doi:10.1111/j.1365-2796.2006.01637.x.PubMedCrossRefGoogle Scholar
  15. 15.
    Mäkinen J, Järvisalo MJ, Pöllänen P, et al. Increased carotid atherosclerosis in andropausal middle-aged men. J Am Coll Cardiol. 2005;45:1603–8. doi:10.1016/j.jacc.2005.01.052.PubMedCrossRefGoogle Scholar
  16. 16.
    van den Beld AW, Bots ML, Janssen JAML, Pols HAP, Lamberts SWJ, Grobbee DE. Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol. 2003;157:25–31. doi:10.1093/aje/kwf160.PubMedCrossRefGoogle Scholar
  17. 17.
    Fu L, Gao QP, Shen JX. Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients. Asian J Androl. 2008;10:214–8. doi:10.1111/j.1745-7262.2008.00335.x.PubMedCrossRefGoogle Scholar
  18. 18.
    Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SWJ, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004;109:2074–9. doi:10.1161/01.CIR.0000125854.51637.06.PubMedCrossRefGoogle Scholar
  19. 19.
    Johnsen SH, Mathiesen EB, Fosse E, Joakimsen O, Stensland-Bugge E, Njølstad I, et al. Elevated high-density lipoprotein cholesterol levels are protective against plaque progression: a follow-up study of 1952 persons with carotid atherosclerosis the Tromsø study. Circulation. 2005;112:498–504. doi:10.1161/CIRCULATIONAHA.104.522706.PubMedCrossRefGoogle Scholar
  20. 20.
    Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666–72. doi:10.1210/jc.84.10.3666.PubMedCrossRefGoogle Scholar
  21. 21.
    Stensland-Bugge E, Bønaa KH, Joakimsen O. Reproducibility of ultrasonographically determined intima-media thickness is dependent on arterial wall thickness: the Tromso study. Stroke. 1997;28:1972–80.PubMedGoogle Scholar
  22. 22.
    Fosse E, Johnsen SH, Stensland-Bugge E, Joakimsen O, Mathiesen EB, Arnesen E, et al. Repeated visual and computer-assisted carotid plaque characterization in a longitudinal population-based ultrasound study: the Tromsø study. Ultrasound Med Biol. 2006;32:3–11. doi:10.1016/j.ultrasmedbio.2005.09.006.PubMedCrossRefGoogle Scholar
  23. 23.
    Hanke H, Lenz C, Hess B, Spindler KD, Weidemann W. Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation. 2001;103:1382–5.PubMedGoogle Scholar
  24. 24.
    Maggio M, Basaria S, Ble A, et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab. 2006;91:345–7. doi:10.1210/jc.2005-1097.PubMedCrossRefGoogle Scholar
  25. 25.
    Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89:3313–8. doi:10.1210/jc.2003-031069.PubMedCrossRefGoogle Scholar
  26. 26.
    Li S, Li X, Li Y. Regulation of atherosclerotic plaque growth and stability by testosterone and its receptor via influence of inflammatory reaction. Vascul Pharmacol. 2008;49:14–8. doi:10.1016/j.vph.2008.03.004.PubMedCrossRefGoogle Scholar
  27. 27.
    De Pergola G, Pannacciulli N, Ciccone M, Tartagni M, Rizzon P, Giorgino R. Free testosterone plasma levels are negatively associated with the intima-media thickness of the common carotid artery in overweight and obese glucose-tolerant young adult men. Int J Obes Relat Metab Disord. 2003;27:803–7. doi:10.1038/sj.ijo.0802292.PubMedCrossRefGoogle Scholar
  28. 28.
    Fukui M, Kitagawa Y, Nakamura N. Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes. Diabetes Care. 2003;26:1869–73. doi:10.2337/diacare.26.6.1869.PubMedCrossRefGoogle Scholar
  29. 29.
    Paraskevas KI, Hamilton G, Mikhailidis DP. Statins: an essential component in the management of carotid artery disease. J Vasc Surg. 2007;46:373–86. doi:10.1016/j.jvs.2007.03.035.PubMedCrossRefGoogle Scholar
  30. 30.
    Kang S, Wu Y, Li X. Effects of statin therapy on the progression of carotid atherosclerosis: a systematic review and meta-analysis. Atherosclerosis. 2004;177:433–42. doi:10.1016/j.atherosclerosis.2004.08.005.PubMedCrossRefGoogle Scholar
  31. 31.
    Hegele RA. The pathogenesis of atherosclerosis. Clin Chim Acta. 1996;246:21–38. doi:10.1016/0009-8981(96)06224-9.PubMedCrossRefGoogle Scholar
  32. 32.
    Barnett PA, Spence JD, Manuck SB, Jennings JR. Psychological stress and the progression of carotid artery disease. J Hypertens. 1997;15:49–55. doi:10.1097/00004872-199715010-00004.PubMedCrossRefGoogle Scholar
  33. 33.
    Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87:589–98. doi:10.1210/jc.87.2.589.PubMedCrossRefGoogle Scholar
  34. 34.
    Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men.Baltimore longitudinal study of aging. J Clin Endocrinol Metab. 2001;86:724–31. doi:10.1210/jc.86.2.724.PubMedCrossRefGoogle Scholar
  35. 35.
    Kley HK, Schlaghecke R, Kruskemper HL. Stability of steroids in plasma over a 10-year period. J Clin Chem Clin Biochem. 1985;23:875–8.PubMedGoogle Scholar
  36. 36.
    Bolelli G, Muti P, Micheli A, Scianjo R, Franceschetti F, Krogh V, et al. Validity for epidemiological studies of long-term cryoconservation of steroid and protein hormones in serum and plasma. Cancer Epidemiol Biomarkers Prev. 1995;4:509–13.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • T. Vikan
    • 1
    • 2
  • S. H. Johnsen
    • 1
    • 3
  • H. Schirmer
    • 4
    • 5
  • I. Njølstad
    • 4
  • J. Svartberg
    • 1
    • 2
  1. 1.Institute of Clinical MedicineUniversity of TromsøTromsøNorway
  2. 2.Department of MedicineUniversity Hospital of North NorwayTromsøNorway
  3. 3.Department of NeurologyUniversity Hospital of North NorwayTromsøNorway
  4. 4.Institute of Community MedicineUniversity of TromsøTromsøNorway
  5. 5.Department of CardiologyUniversity Hospital of North NorwayTromsøNorway

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