(Circulation. 2000;102:1906.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Low-Dose Transdermal Testosterone Therapy Improves Angina Threshold in Men With Chronic Stable Angina
A Randomized, Double-Blind, Placebo-Controlled Study
From the Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK (K.M.E., R.P.S., K.S.C.); Department of Human Metabolism and Clinical Biochemistry, University of Sheffield, Sheffield, and Barnsley District General Hospital, Barnsley, South Yorkshire (T.H.J.); and Department of Clinical Chemistry, University of Liverpool, Liverpool, UK (M.J.D.).
Background—Experimental studies suggest that androgens induce coronary vasodilatation. We performed this pilot project to examine the clinical effects of long-term low-dose androgens in men with angina.
Methods and Results—Forty-six men with stable angina completed a 2-week, single-blind placebo run-in, followed by double-blind randomization to 5 mg testosterone daily by transdermal patch or matching placebo for 12 weeks, in addition to their current medication. Time to 1-mm ST-segment depression on treadmill exercise testing and hormone levels were measured and quality of life was assessed by SF-36 at baseline and after 4 and 12 weeks of treatment. Active treatment resulted in a 2-fold increase in androgen levels and an increase in time to 1-mm ST-segment depression from (mean±SEM) 309±27 seconds at baseline to 343±26 seconds after 4 weeks and to 361±22 seconds after 12 weeks. This change was statistically significant compared with that seen in the placebo group (from 266±25 seconds at baseline to 284±23 seconds after 4 weeks and to 292±24 seconds after 12 weeks; P=0.02 between the 2 groups by ANCOVA). The magnitude of the response was greater in those with lower baseline levels of bioavailable testosterone (r=-0.455, P<0.05). There were no significant changes in prostate specific antigen, hemoglobin, lipids, or coagulation profiles during the study. There were significant improvements in pain perception (P=0.026) and role limitation resulting from physical problems (P=0.024) in the testosterone-treated group.
Conclusions—Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia.
Key Words: testosterone • hormones • angina • ischemia
This article has been cited by other articles:
 |
|
 |
|
  P. Romerius, O. Stahl, C. Moell, T. Relander, E. Cavallin-Stahl, T. Wiebe, Y. L. Giwercman, and A. Giwercman Hypogonadism Risk in Men Treated for Childhood Cancer J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4180 - 4186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vikan, H. Schirmer, I. Njolstad, and J. Svartberg Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromso Study Eur. J. Endocrinol., September 1, 2009; 161(3): 435 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mathur, C. Malkin, B. Saeed, R Muthusamy, T H. Jones, and K. Channer Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men Eur. J. Endocrinol., September 1, 2009; 161(3): 443 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Traish, F. Saad, R. J. Feeley, and A. Guay The Dark Side of Testosterone Deficiency: III. Cardiovascular Disease J Androl, September 1, 2009; 30(5): 477 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Jackson CHAPTER 15c Erectile Dysfunction ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. V. Getov, R. W. Lee, F. Dockery, and C. Rajkumar Androgens, ageing and vascular function Age Ageing, July 1, 2008; 37(4): 361 - 363. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Martorell, J. Blanco-Rivero, R. Aras-Lopez, A. Sagredo, G. Balfagon, and M. Ferrer Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta Cardiovasc Res, February 1, 2008; 77(3): 590 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Basaria and A. S. Dobs Testosterone Making an Entry Into the Cardiometabolic World Circulation, December 4, 2007; 116(23): 2658 - 2661. [Full Text] [PDF]
|
|
|
|
|
|
K.-T. Khaw, M. Dowsett, E. Folkerd, S. Bingham, N. Wareham, R. Luben, A. Welch, and N. Day Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men: European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study Circulation, December 4, 2007; 116(23): 2694 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Lujan, V. J. Kramer, and S. E. DiCarlo Sex influences the susceptibility to reperfusion-induced sustained ventricular tachycardia and beta-adrenergic receptor blockade in conscious rats Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2799 - H2808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P. Liu and M. Fukuoka Sex Hormones as Novel Risk Biomarkers for Atherosclerosis in Peripheral Vascular Disease J. Am. Coll. Cardiol., September 11, 2007; 50(11): 1077 - 1079. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Malkin, T. H. Jones, and K. S. Channer The effect of testosterone on insulin sensitivity in men with heart failure Eur J Heart Fail, January 1, 2007; 9(1): 44 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Isidori and A. Lenzi Testosterone Replacement Therapy: What We Know Is Not Yet Enough Mayo Clin. Proc., January 1, 2007; 82(1): 11 - 13. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Haddad, C. C. Kennedy, S. M. Caples, M. J. Tracz, E. R. Bolona, K. Sideras, M. V. Uraga, P. J. Erwin, and V. M. Montori Testosterone and Cardiovascular Risk in Men: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials Mayo Clin. Proc., January 1, 2007; 82(1): 29 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, S. Tsang, and T. M. Wong Testosterone Is Required for Delayed Cardioprotection and Enhanced Heat Shock Protein 70 Expression Induced by Preconditioning Endocrinology, October 1, 2006; 147(10): 4569 - 4577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Shores, A. M. Matsumoto, K. L. Sloan, and D. R. Kivlahan Low Serum Testosterone and Mortality in Male Veterans. Arch Intern Med, August 14, 2006; 166(15): 1660 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Matthiesson and R. I. McLachlan Male hormonal contraception: concept proven, product in sight? Hum. Reprod. Update, July 1, 2006; 12(4): 463 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Kapoor, E Goodwin, K S Channer, and T H Jones Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur. J. Endocrinol., June 1, 2006; 154(6): 899 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhasin, G. R. Cunningham, F. J. Hayes, A. M. Matsumoto, P. J. Snyder, R. S. Swerdloff, and V. M. Montori Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 1995 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hall, R. D. Jones, T. H. Jones, K. S. Channer, and C. Peers Selective Inhibition of L-Type Ca2+ Channels in A7r5 Cells by Physiological Levels of Testosterone Endocrinology, June 1, 2006; 147(6): 2675 - 2680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bernini, D. Versari, A. Moretti, A. Virdis, L. Ghiadoni, M. Bardini, C. Taurino, D. Canale, S. Taddei, and A. Salvetti Vascular Reactivity in Congenital Hypogonadal Men before and after Testosterone Replacement Therapy J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1691 - 1697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Norata, G. Tibolla, P. M. Seccomandi, A. Poletti, and A. L. Catapano Dihydrotestosterone Decreases Tumor Necrosis Factor-{alpha} and Lipopolysaccharide-Induced Inflammatory Response in Human Endothelial Cells J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Malkin, P. J. Pugh, J. N. West, E. J.R. van Beek, T. H. Jones, and K. S. Channer Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial Eur. Heart J., January 1, 2006; 27(1): 57 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Calof, A. B. Singh, M. L. Lee, A. M. Kenny, R. J. Urban, J. L. Tenover, and S. Bhasin Adverse Events Associated With Testosterone Replacement in Middle-Aged and Older Men: A Meta-Analysis of Randomized, Placebo-Controlled Trials J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2005; 60(11): 1451 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kaufman and A. Vermeulen The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications Endocr. Rev., October 1, 2005; 26(6): 833 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Mishra, R. K. Hermsmeyer, K. Miyagawa, P. Sarrel, B. Uchida, F. Z. Stanczyk, K. A. Burry, D. R. Illingworth, and F. J. Nordt Medroxyprogesterone Acetate and Dihydrotestosterone Induce Coronary Hyperreactivity in Intact Male Rhesus Monkeys J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3706 - 3714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A M Smith, K M English, C J Malkin, R D Jones, T H Jones, and K S Channer Testosterone does not adversely affect fibrinogen or tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels in 46 men with chronic stable angina Eur. J. Endocrinol., February 1, 2005; 152(2): 285 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Yang, G. W. Barsness, B. J. Gersh, K. Chandrasekaran, and A. Lerman Current and Future Treatment Strategies for Refractory Angina Mayo Clin. Proc., October 1, 2004; 79(10): 1284 - 1292. [Abstract] [PDF]
|
|
|
|
|
|
E. Nieschlag, H.M. Behre, P. Bouchard, J.J. Corrales, T.H. Jones, G.K. Stalla, S.M. Webb, and F.C.W. Wu Testosterone replacement therapy: current trends and future directions Hum. Reprod. Update, September 1, 2004; 10(5): 409 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C J Malkin, P J Pugh, P D Morris, K E Kerry, R D Jones, T H Jones, and K S Channer Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life Heart, August 1, 2004; 90(8): 871 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Malkin, P. J. Pugh, R. D. Jones, D. Kapoor, K. S. Channer, and T. H. Jones The Effect of Testosterone Replacement on Endogenous Inflammatory Cytokines and Lipid Profiles in Hypogonadal Men J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3313 - 3318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morgentaler A 66-Year-Old Man With Sexual Dysfunction JAMA, June 23, 2004; 291(24): 2994 - 3003. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Littleton-Kearney and P. D. Hurn Testosterone as a Modulator of Vascular Behavior Biol Res Nurs, April 1, 2004; 5(4): 276 - 285. [Abstract] [PDF]
|
|
|
|
 |
|
 E. L. Rhoden and A. Morgentaler Risks of Testosterone-Replacement Therapy and Recommendations for Monitoring N. Engl. J. Med., January 29, 2004; 350(5): 482 - 492. [Full Text] [PDF]
|
|
|
|
|
|
M. Muller, Y. T. van der Schouw, J. H. H. Thijssen, and D. E. Grobbee Endogenous Sex Hormones and Cardiovascular Disease in Men J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5076 - 5086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.J. Malkin, P.J. Pugh, T.H. Jones, and K.S. Channer Testosterone for secondary prevention in men with ischaemic heart disease? QJM, July 1, 2003; 96(7): 521 - 529. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Morley The Need for a Men's Health Initiative J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): M614 - 617. [Full Text] [PDF]
|
|
|
|
|
|
P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bhasin and K. Herbst Testosterone and Atherosclerosis Progression in Men Diabetes Care, June 1, 2003; 26(6): 1929 - 1931. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Pugh, T. H. Jones, and K. S. Channer Acute haemodynamic effects of testosterone in men with chronic heart failure Eur. Heart J., May 2, 2003; 24(10): 909 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. W. Wu and A. von Eckardstein Androgens and Coronary Artery Disease Endocr. Rev., April 1, 2003; 24(2): 183 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Jones, C. J. Malkin, K. S. Channer, and T. H. Jones Low Levels of Endogenous Androgens Increase the Risk of Atherosclerosis in Elderly Men: Further Supportive Data J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1403 - 1404. [Full Text]
|
|
|
|
|
|
K S Channer and T H Jones Cardiovascular effects of testosterone: implications of the "male menopause"? Heart, February 1, 2003; 89(2): 121 - 122. [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Mukherjee, H. Dinh, G. Chaudhuri, and L. Nathan Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: Implications in atherosclerosis PNAS, March 19, 2002; 99(6): 4055 - 4060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Matsumoto Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99. [Full Text]
|
|
|
|
|
|
M. Cattaneo, D. N. Kiortsis, M. S. Elisaf, K.M. English, P.J. Pugh, K.S. Channer, S. C. Clarke, P. M. Schofield, A. A. Grace, J. C. Metcalfe, et al. Does Tamoxifen Enhance Endothelial Function by Lowering the Plasma Levels of Homocysteine? Effects of Tamoxifen on Endothelial Function and Cardiovascular Risk Factors in Men With Advanced Atherosclerosis Effects of Tamoxifen on Endothelial Function and Cardiovascular Risk Factors in Men With Advanced Atherosclerosis Response Circulation, December 11, 2001; 104 (24): e146 - e147. [Full Text] [PDF]
|
|
|
|
|
|
A. Vermeulen Androgen Replacement Therapy in the Aging Male--A Critical Evaluation J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2380 - 2390. [Full Text] [PDF]
|
|
|
|
 |
|
 Testosterone Improves Angina Threshold Journal Watch Cardiology, December 15, 2000; 2000(1215): 13 - 13. [Full Text]
|
|
|
|
 |
|
 Testosterone Improves Angina Threshold Journal Watch (General), November 3, 2000; 2000(1103): 5 - 5. [Full Text]
|
|