Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease

Carolyn M Webb, Andrew G Elkington, Mustafa M Kraidly, Niall Keenan, Dudley J Pennell, Peter Collins, Carolyn M Webb, Andrew G Elkington, Mustafa M Kraidly, Niall Keenan, Dudley J Pennell, Peter Collins

Abstract

Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow. Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease. However, the effects on myocardial perfusion are unknown. Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone. Twenty-two men (mean age 57 +/- 9 [SD] years) were randomly assigned to oral testosterone undecanoate (TU; 80 mg twice daily) or placebo in a crossover study design. After each 8-week period, subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance, pulse-wave analysis, and endothelial function measurements using radial artery tonometry, blood sampling, anthropomorphic measurements, and quality-of-life assessment. Although no difference was found in global myocardial perfusion after TU compared with placebo, myocardium supplied by unobstructed coronary arteries showed increased perfusion (1.83 +/- 0.9 vs 1.52 +/- 0.65; p = 0.037). TU decreased basal radial and aortic augmentation indexes (p = 0.03 and p = 0.02, respectively), indicating decreased arterial stiffness, but there was no effect on endothelial function. TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference, but had no effect on hemostatic factors, quality of life, and angina symptoms. In conclusion, oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries, in line with previous intracoronary findings. The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia.

Figures

Figure 1
Figure 1
Bar graph shows mean myocardial perfusion index for placebo (black bars) and TU (hatched bars) for myocardial regions associated with angiographically documented significant coronary atheroma or perfusion defect on preenrollment thallium scan and remaining “normal” regions. Subendo = subendocardial; subepi = subepicardial.
Figure 2
Figure 2
Bar graph shows radial augmentation index at baseline, 20 minutes after inhaled salbutamol, and 5 minutes after sublingual glyceryl trinitrate for placebo (black bars) and TU (hatched bars).

References

    1. Wu F.C., von Eckardstein A. Androgens and coronary artery disease. Endocr Rev. 2003;24:183–217.
    1. Webb C.M., McNeill J.G., Hayward C.S., de Ziegler D., Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary artery disease. Circulation. 1999;100:1690–1696.
    1. English K.M., Steeds R.P., Jones T.H., Diver M.J., Channer K.S. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation. 2000;102:1906–1911.
    1. Christian T.F., Rettmann D.W., Aletras A.H., Liao S.L., Taylor J.L., Balaban R.S., Arai A.E. Absolute myocardial perfusion in canines measured by using dual-bolus first-pass MR imaging. Radiology. 2004;232:677–684.
    1. Elkington A.G., Ablitt N.A., Yang G.Z., Firmin D.N., Pennell D.J. Interstudy reproducibility of quantitative perfusion cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2005;7:815–822.
    1. Maceira A.M., Prasad S.K., Khan M., Pennell D.J. Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2006;8:417–426.
    1. Jerosch-Herold M., Wilke N., Stillman A.E. Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med Phys. 1988;25:73–84.
    1. Hayward C.S., Kraidly M., Webb C.M., Collins P. Assessment of endothelial function using peripheral waveform analysis: A clinical application. J Am Coll Cardiol. 2002;40:521–528.
    1. Stewart A.L., Hays R.D., Ware J.E., Jr The MOS short-form general health survey: Reliability and validity in a patient population. Med Care. 1988;26:724–735.
    1. Wahrborg P., Emanuelsson H. The Cardiac Health Profile: content, reliability and validity of a new disease-specific quality of life questionnaire. Coron Artery Dis. 1996;7:823–829.
    1. Daig I., Heinemann L.A., Kim S., Leungwattanakij S., Badia X., Myon E., Moore C., Saad F., Potthoff P., Thai D.M. The Aging Males’ Symptoms (AMS) Scale: review of its methodological characteristics. Health Qual Life Outcomes. 2003;1:77.
    1. London G., Guerin A., Pannier B., Marchais S., Benetos A., Safar M. Increased systolic pressure in chronic uremia: Role of arterial wave reflections. Hypertension. 1992;20:10–19.
    1. Panting J.R., Gatehouse P.D., Yang G.Z., Grothues F., Firmin D.N., Collins P., Pennell D.J. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med. 2002;346:1948–1953.
    1. Ahimastos A.A., Formosa M., Dart A.M., Kingwell B.A. Gender differences in large artery stiffness pre- and post puberty. J Clin Endocrinol Metab. 2003;88:5375–5380.
    1. Hougaku H., Fleg J.L., Najjar S.S., Lakatta E.G., Harman S.M., Blackman M.R., Metter E.J. Relationship between androgenic hormones and arterial stiffness based on longitudinal hormone measurements. Am J Physiol. 2006;290:E234–E242.
    1. Willum-Hansen T., Staessen J.A., Torp-Pedersen C., Rasmussen S., Thijs L., Ibsen H., Jeppesen J. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation. 2006;113:664–670.
    1. Mattace-Raso F.U., van der Cammen T.J., Hofman A., van Popele N.M., Bos M.L., Schalekamp M.A., Asmar R., Reneman R.S., Hoeks A.P., Breteler M.M., Witteman J.C. Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation. 2006;113:657–663.
    1. Kang S.M., Jang Y., Kim J.Y., Chung N., Cho S.Y., Chae J.S., Lee J.H. Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. Am J Cardiol. 2002;89:862–864.
    1. Orshal J.M., Khalil R.A. Gender, sex hormones, and vascular tone. Am J Physiol. 2004;286:R233–R249.
    1. Gonzales R.J., Ghaffari A.A., Duckles S.P., Krause D.N. Testosterone treatment increases thromboxane function in rat cerebral arteries. Am J Physiol. 2005;289:H578–H585.
    1. Dobrzycki S., Serwatka W., Nadlewski S., Korecki J., Jackowski R., Paruk J., Ladny J.R., Hirnle T. An assessment of correlations between endogenous sex hormone levels and the extensiveness of coronary heart disease and the ejection fraction of the left ventricle in males. J Med Invest. 2003;50:162–169.
    1. Golden K.L., Marsh J.D., Jiang Y., Brown T., Moulden J. Gonadectomy of adult male rats reduces contractility of isolated cardiac myocytes. Am J Physiol. 2003;285:E449–E453.
    1. Scheuer J., Malhotra A., Schaible T.F., Capasso J. Effects of gonadectomy and hormonal replacement on rat hearts. Circ Res. 1987;61:12–19.
    1. Schaible T.F., Malhotra A., Ciambrone G., Scheuer J. The effects of gonadectomy on left ventricular function and cardiac contractile proteins in male and female rats. Circ Res. 1984;54:38–49.
    1. Nieschlag E., Mauss J., Coert A., Kicovic P. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol. 1975;79:366–374.
    1. Hirschhauser C., Hopkinson C.R., Sturm G., Coert A. Testosterone undecanoate: a new orally active androgen. Acta Endocrinol. 1975;80:179–187.
    1. Jaffe M.D. Effect of testosterone cypionate on postexercise ST segment depression. Br Heart J. 1977;39:1217–1222.

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