(Circulation. 1999;100:1690-1696.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart Disease
From Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, and Royal Brompton Hospital, London, UK (C.M.W., J.G.M., C.S.H., P.C.), and Columbia Laboratories, Paris, France (D.d.Z).
Correspondence to Dr Peter Collins, Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK. E-mail peter.collins{at}ic.ac.uk
Background—The increased incidence of coronary artery disease in men compared with premenopausal women suggests a detrimental role of male hormones on the cardiovascular system. However, testosterone has direct relaxing effects on coronary arteries in animals, as shown both in vitro and in vivo. The effect of testosterone on the human coronary circulation remains unknown.
Methods and Results—We studied 13 men (aged 61±11 years) with coronary artery disease. They underwent measurement of coronary artery diameter and blood flow after a 3-minute intracoronary infusion of vehicle control (ethanol) followed by 2-minute intracoronary infusions of acetylcholine (10-7 to 10-5 mol/L) until peak velocity response. A dose-response curve to 3-minute infusions of testosterone (10-10 to 10-7 mol/L) was then determined, and the acetylcholine infusions were repeated. Finally, an intracoronary bolus of isosorbide dinitrate (1000 µg) was given. Coronary blood flow was calculated from measurements of blood flow velocity using intracoronary Doppler and coronary artery diameter using quantitative coronary angiography. Testosterone significantly increased coronary artery diameter compared with baseline (2.78±0.74 mm versus 2.86±0.72 mm [P=0.05], 2.87±0.71 mm [P=0.038], and 2.90±0.75 mm [P=0.005] for baseline versus testosterone 10-9 to 10-7 mol/L, respectively). A significant increase in coronary blood flow occurred at all concentrations of testosterone compared with baseline (geometric mean [95% CI]: 32 [25, 42] versus 36.3 [27, 48] {P=0.006}, 35.3 [26, 47] {P=0.029}, 36.8 [28, 49] {P=0.002}, and 37 [28, 48] {P=0.002} mL/min for baseline versus testosterone 10-10 to 10-7 mol/L, respectively). No differences existed in coronary diameter or blood flow responses to acetylcholine before versus after testosterone.
Conclusions—Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.
Key Words: coronary arteries • testosterone • blood flow
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 D. L. Tharp, I. Masseau, J. Ivey, V. K. Ganjam, and D. K. Bowles Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine Cardiovasc Res, April 1, 2009; 82(1): 152 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Carrero, A. R. Qureshi, P. Parini, S. Arver, B. Lindholm, P. Barany, O. Heimburger, and P. Stenvinkel Low Serum Testosterone Increases Mortality Risk among Male Dialysis Patients J. Am. Soc. Nephrol., March 1, 2009; 20(3): 613 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Yassin and F. Saad Testosterone and Erectile Dysfunction J Androl, November 1, 2008; 29(6): 593 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mancini, E. Leone, R. Festa, G. Grande, A. Silvestrini, L. de Marinis, A. Pontecorvi, G. Maira, G. P. Littarru, and E. Meucci Effects of Testosterone on Antioxidant Systems in Male Secondary Hypogonadism J Androl, November 1, 2008; 29(6): 622 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Montano, E. Calixto, A. Figueroa, E. Flores-Soto, V. Carbajal, and M. Perusquia Relaxation of Androgens on Rat Thoracic Aorta: Testosterone Concentration Dependent Agonist/Antagonist L-Type Ca2+ Channel Activity, and 5{beta}-Dihydrotestosterone Restricted to L-Type Ca2+ Channel Blockade Endocrinology, May 1, 2008; 149(5): 2517 - 2526. [Abstract] [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]
|
|
|
|
 |
|
 D. S. Hydock, C.-Y. Lien, C. M. Schneider, and R. Hayward Effects of voluntary wheel running on cardiac function and myosin heavy chain in chemically gonadectomized rats Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3254 - H3264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Bowles, K. K. Maddali, V. C. Dhulipala, and D. H. Korzick PKC{delta} mediates anti-proliferative, pro-apoptic effects of testosterone on coronary smooth muscle Am J Physiol Cell Physiol, August 1, 2007; 293(2): C805 - C813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J Pearson, C. Rait, M G. Nicholls, T. G Yandle, and J. J Evans Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II. J. Endocrinol., October 1, 2006; 191(1): 171 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Braga-Basaria, A. S. Dobs, D. C. Muller, M. A. Carducci, M. John, J. Egan, and S. Basaria Metabolic Syndrome in Men With Prostate Cancer Undergoing Long-Term Androgen-Deprivation Therapy J. Clin. Oncol., August 20, 2006; 24(24): 3979 - 3983. [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]
|
|
|
|
 |
|
 C. J. Abularrage, A. N. Sidawy, G. Aidinian, N. Singh, J. M. Weiswasser, and S. Arora Evaluation of Macrocirculatory Endothelium-Dependent and Endothelium-Independent Vasoreactivity in Vascular Disease Perspectives in Vascular Surgery and Endovascular Therapy, September 1, 2005; 17(3): 245 - 253. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Meyer, B. P. McGrath, J. Cameron, D. Kotsopoulos, and H. J. Teede Vascular Dysfunction and Metabolic Parameters in Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4630 - 4635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Gonzales, A. A. Ghaffari, S. P. Duckles, and D. N. Krause Testosterone treatment increases thromboxane function in rat cerebral arteries Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H578 - H585. [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]
|
|
|
|
|
|
D. K. Bowles, K. K. Maddali, V. K. Ganjam, L. J. Rubin, D. L. Tharp, J. R. Turk, and C. L. Heaps Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2091 - H2098. [Abstract] [Full Text] [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]
|
|
|
|
|
|
A. Sierra-Ramirez, T. Morato, R. Campos, I. Rubio, C. Calzada, E. Mendez, and G. Ceballos Acute effects of testosterone on intracellular Ca2+ kinetics in rat coronary endothelial cells are exerted via aromatization to estrogens Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H63 - H71. [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]
|
|
|
|
|
|
R. J. Gonzales, D. N. Krause, and S. P. Duckles Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H552 - H560. [Abstract] [Full Text] [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]
|
|
|
|
|
|
F. Callies, H. Stromer, R. H. G. Schwinger, B. Bolck, K. Hu, S. Frantz, A. Leupold, S. Beer, B. Allolio, and A. W. Bonz Administration of Testosterone Is Associated with a Reduced Susceptibility to Myocardial Ischemia Endocrinology, October 1, 2003; 144(10): 4478 - 4483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chatrath, K. L. Ronningen, S. R. Severson, P. LaBreche, M. Jayachandran, M. P. Bracamonte, and V. M. Miller Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1168 - H1176. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 M. Fukui, Y. Kitagawa, N. Nakamura, M. Kadono, S. Mogami, C. Hirata, N. Ichio, K. Wada, G. Hasegawa, and T. Yoshikawa Association Between Serum Testosterone Concentration and Carotid Atherosclerosis in Men With Type 2 Diabetes Diabetes Care, June 1, 2003; 26(6): 1869 - 1873. [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]
|
|
|
|
|
|
M. Zitzmann, M. Brune, and E. Nieschlag Vascular Reactivity in Hypogonadal Men Is Reduced by Androgen Substitution J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5030 - 5037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Molinari, A Battaglia, E Grossini, D A S G Mary, C Vassanelli, and G Vacca The effect of testosterone on regional blood flow in prepubertal anaesthetized pigs J. Physiol., August 15, 2002; 543(1): 365 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann, R. Junker, A. Kamischke, and E. Nieschlag Contraceptive Steroids Influence the Hemostatic Activation State in Healthy Men J Androl, July 1, 2002; 23(4): 503 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Kenny, K. M. Prestwood, C. A. Gruman, G. Fabregas, B. Biskup, and G. Mansoor Effects of Transdermal Testosterone on Lipids and Vascular Reactivity in Older Men With Low Bioavailable Testosterone Levels J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2002; 57(7): M460 - 465. [Abstract] [Full Text]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
M. A. Sader and D. S. Celermajer Endothelial function, vascular reactivity and gender differences in the cardiovascular system Cardiovasc Res, February 15, 2002; 53(3): 597 - 604. [Full Text] [PDF]
|
|
|
|
|
|
R. K. Dubey, S. Oparil, B. Imthurn, and E. K. Jackson Sex hormones and hypertension Cardiovasc Res, February 15, 2002; 53(3): 688 - 708. [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]
|
|
|
|
 |
|
 S.-H. Yang, E. Perez, J. Cutright, R. Liu, Z. He, A. L. Day, and J. W. Simpkins Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model J Appl Physiol, January 1, 2002; 92(1): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann, M. Brune, B. Kornmann, J. Gromoll, S. von Eckardstein, A. von Eckardstein, and E. Nieschlag The CAG Repeat Polymorphism in the AR Gene Affects High Density Lipoprotein Cholesterol and Arterial Vasoreactivity J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4867 - 4873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Smith, S. Bennett, L. M. Evans, H. G. Kynaston, M. Parmar, M. D. Mason, J. R. Cockcroft, M. F. Scanlon, and J. S. Davies The Effects of Induced Hypogonadism on Arterial Stiffness, Body Composition, and Metabolic Parameters in Males with Prostate Cancer J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4261 - 4267. [Abstract] [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]
|
|
|
|
|
|
H. Hanke, C. Lenz, B. Hess, K.-D. Spindler, and W. Weidemann Effect of Testosterone on Plaque Development and Androgen Receptor Expression in the Arterial Vessel Wall Circulation, March 13, 2001; 103(10): 1382 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Dobs, P. S. Bachorik, S. Arver, A. W. Meikle, S. W. Sanders, K. E. Caramelli, and N. A. Mazer Interrelationships among Lipoprotein Levels, Sex Hormones, Anthropometric Parameters, and Age in Hypogonadal Men Treated for 1 Year with a Permeation-Enhanced Testosterone Transdermal System J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1026 - 1033. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. A. Sader, K. A. Griffiths, R. J. McCredie, D. J. Handelsman, and D. S. Celermajer Androgenic anabolic steroids and arterial structure and function in male bodybuilders J. Am. Coll. Cardiol., January 1, 2001; 37(1): 224 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Worboys, D. Kotsopoulos, H. Teede, B. McGrath, and S. R. Davis Evidence That Parenteral Testosterone Therapy May Improve Endothelium-Dependent and -Independent Vasodilation in Postmenopausal Women Already Receiving Estrogen J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 158 - 161. [Abstract] [Full Text]
|
|
|
|
|
|
K. M. English, R. P. Steeds, T. H. Jones, M. J. Diver, and K. S. Channer Low-Dose Transdermal Testosterone Therapy Improves Angina Threshold in Men With Chronic Stable Angina : A Randomized, Double-Blind, Placebo-Controlled Study Circulation, October 17, 2000; 102(16): 1906 - 1911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Webb, M. A. Ghatei, J. G. McNeill, DCRR, and P. Collins 17{beta}-Estradiol Decreases Endothelin-1 Levels in the Coronary Circulation of Postmenopausal Women With Coronary Artery Disease Circulation, October 3, 2000; 102(14): 1617 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.J. Pugh, K.M. English, T.H. Jones, and K.S. Channer Testosterone: a natural tonic for the failing heart? QJM, October 1, 2000; 93(10): 689 - 694. [Full Text] [PDF]
|
|
|
|
|
|
G. G. Geary, D. N. Krause, and S. P. Duckles Gonadal hormones affect diameter of male rat cerebral arteries through endothelium-dependent mechanisms Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H610 - H618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.M.C. Rosano Androgens and coronary artery disease. A sex-specific effect of sex hormones? Eur. Heart J., June 1, 2000; 21(11): 868 - 871. [PDF]
|
|
|
|
|
|
K.M English, O Mandour, R.P Steeds, M.J Diver, T.H Jones, and K.S Channer Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms Eur. Heart J., June 1, 2000; 21(11): 890 - 894. [Abstract] [PDF]
|
|
|
|
|
|
C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]
|
|