Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2004-2009
© 1997 American Heart Association, Inc.
Articles |
Androgen Deprivation Is Associated With Enhanced Endothelium-Dependent Dilatation in Adult Men
From the Departments of Cardiology (S.M.H., J.T.C.R., R.J.M., M.R.A., D.S.C.) and Medical Oncology (M.J.B.), Royal Prince Alfred Hospital, and the Heart Research Institute (J.T.C.R., R.J.M., D.S.C.), Sydney, Australia.
Correspondence to A/Prof David Celermajer, Medical Foundation Fellow, University of Sydney, Department of Cardiology, Royal Prince Alfred Hospital, Camperdown 2050, Sydney, Australia. Email davidc{at}card.rpa.cs.nsw.gov.au
Abstract Male gender is an independent risk factor for
coronary artery disease, and androgen administration has been
associated with increased atherosclerosis in
experimental animals. Since endothelial dysfunction is
an important event in the atherogenic process, we hypothesized that
androgen deprivation in adult men might be associated with
enhanced arterial endothelial function.
Using external vascular ultrasound, brachial artery diameter was
measured at rest, after flow increase (causing
endothelium-dependent dilatation) and after
nitroglycerin (an
endothelium-independent dilator). We studied 30 adult
males aged 40 to 70 years: 10 had had bilateral orchidectomy and/or
maximal androgen blockade for 
6 months for treatment of prostate
cancer, and all were in complete remission (group 1). Ten healthy
controls (group 2) and 10 controls who had remission from nonprostate
cancers (group 3) were matched for age and smoking history.
Testosterone levels were lower in men in group 1 versus groups 2 or 3
(0.8±0.1 versus 19.2±8.4 or 16.1±4.9 nmol/L, P<.001). By
contrast, endothelium-dependent dilatation was markedly
higher in group 1 than in groups 2 or 3 (6.2±3 versus 2.7±2 or
2.0±1.9%, P<.001). The nitroglycerin
response was similar in all three groups (P=.92). On
multivariate analysis, increased
endothelium-dependent dilatation was significantly
associated with low serum testosterone levels (P=.001) but
not with cholesterol levels or with a past history of
malignancy (P>.25). The withdrawal of male sex hormones may
be associated with enhanced endothelial function in
adult men. This is consistent with a deleterious effect of
physiologic levels of male sex steroids on the arterial
wall.
Key Words: endothelium • nitric oxide • testosterone • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  M. Yaron, Y. Greenman, J. B Rosenfeld, E. Izkhakov, R. Limor, E. Osher, G. Shenkerman, K. Tordjman, and N. Stern Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men Eur. J. Endocrinol., May 1, 2009; 160(5): 839 - 846. [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]
|
|
|
|
 |
|
 J. R. Meendering, B. N. Torgrimson, N. P. Miller, P. F. Kaplan, and C. T. Minson Estrogen, medroxyprogesterone acetate, endothelial function, and biomarkers of cardiovascular risk in young women Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1630 - H1637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Pepine, W. W. Nichols, and D. F. Pauly Estrogen and Different Aspects of Vascular Disease in Women and Men Circ. Res., September 1, 2006; 99(5): 459 - 461. [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]
|
|
|
|
 |
|
 C. J. Pepine, R. A. Kerensky, C. R. Lambert, K. M. Smith, G. O. von Mering, G. Sopko, and C. N. Bairey Merz Some Thoughts on the Vasculopathy of Women With Ischemic Heart Disease J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S30 - S35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lakhani, A. Leonard, A.M. Seifalian, and P. Hardiman Microvascular dysfunction in women with polycystic ovary syndrome Hum. Reprod., November 1, 2005; 20(11): 3219 - 3224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Razmara, D. N. Krause, and S. P. Duckles Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1843 - H1850. [Abstract] [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]
|
|
|
|
 |
|
 Z. F. Ba, Y. Yokoyama, B. Toth, L. W. Rue III, K. I. Bland, and I. H. Chaudry Gender differences in small intestinal endothelial function: inhibitory role of androgens Am J Physiol Gastrointest Liver Physiol, March 1, 2004; 286(3): G452 - G457. [Abstract] [Full Text] [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. A. Ahimastos, M. Formosa, A. M. Dart, and B. A. Kingwell Gender Differences in Large Artery Stiffness Pre- and Post Puberty J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5375 - 5380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Chatrath, K. L. Ronningen, P. LaBreche, S. R. Severson, M. Jayachandran, M. P. Bracamonte, and V. M. Miller Effect of puberty on coronary arteries from female pigs J Appl Physiol, October 1, 2003; 95(4): 1672 - 1680. [Abstract] [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]
|
|
|
|
|
|
N. A. Herity, S. Lo, D. P. Lee, M. R. Ward, S. D. Filardo, P. G. Yock, P. J. Fitzgerald, S. A. Hunt, and A. C. Yeung Effect of a change in gender on coronary arterial size: A longitudinal intravascular ultrasound study in transplanted hearts J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1539 - 1546. [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]
|
|
|
|
 |
|
 T. A. Taylor, C. E. Gariepy, D. M. Pollock, and J. S. Pollock Gender Differences in ET and NOS Systems in ETB Receptor-Deficient Rats: Effect of a High Salt Diet Hypertension, March 1, 2003; 41(3): 657 - 662. [Abstract] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
R. Joannides, A. Costentin, M. Iacob, P. Compagnon, A. Lahary, and C. Thuillez Influence of vascular dimension on gender difference in flow-dependent dilatation of peripheral conduit arteries Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1262 - H1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ling, A. Dai, M. R. I. Williams, K. Myles, R. J. Dilley, P. A. Komesaroff, and K. Sudhir Testosterone (T) Enhances Apoptosis-Related Damage in Human Vascular Endothelial Cells Endocrinology, March 1, 2002; 143(3): 1119 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E Rossouw Hormones, genetic factors, and gender differences in cardiovascular disease Cardiovasc Res, February 15, 2002; 53(3): 550 - 557. [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]
|
|
|
|
|
|
P. A. Komesaroff, M. Fullerton, M. D. Esler, A. Dart, G. Jennings, and K. Sudhir Low-Dose Estrogen Supplementation Improves Vascular Function in Hypogonadal Men Hypertension, November 1, 2001; 38(5): 1011 - 1016. [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]
|
|
|
|
|
|
L. P. Ly, M. Jimenez, T. N. Zhuang, D. S. Celermajer, A. J. Conway, and D. J. Handelsman A Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Transdermal Dihydrotestosterone Gel on Muscular Strength, Mobility, and Quality of Life in Older Men with Partial Androgen Deficiency J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4078 - 4088. [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]
|
|
|
|
 |
|
 G. Paradisi, H. O. Steinberg, A. Hempfling, J. Cronin, G. Hook, M. K. Shepard, and A. D. Baron Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction Circulation, March 13, 2001; 103(10): 1410 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 A. M. G. Verhagen, D. M. A. Attia, H. A. Koomans, and J. A. Joles Male gender increases sensitivity to proteinuria induced by mild NOS inhibition in rats: role of sex hormones Am J Physiol Renal Physiol, October 1, 2000; 279(4): F664 - F670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. O. Steinberg, G. Paradisi, J. Cronin, K. Crowde, A. Hempfling, G. Hook, and A. D. Baron Type II Diabetes Abrogates Sex Differences in Endothelial Function in Premenopausal Women Circulation, May 2, 2000; 101(17): 2040 - 2046. [Abstract] [Full Text] [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]
|
|
|
|
|
|
H. Teoh, A. Quan, and R. Y.K Man Acute impairment of relaxation by low levels of testosterone in porcine coronary arteries Cardiovasc Res, March 1, 2000; 45(4): 1010 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. McCrohon, A. K. Death, S. Nakhla, W. Jessup, D. J. Handelsman, K. K. Stanley, and D. S. Celermajer Androgen Receptor Expression Is Greater in Macrophages From Male Than From Female Donors : A Sex Difference With Implications for Atherogenesis Circulation, January 25, 2000; 101(3): 224 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Lotufo, C. U. Chae, U. A. Ajani, C. H. Hennekens, and J. E. Manson Male Pattern Baldness and Coronary Heart Disease: The Physicians' Health Study Arch Intern Med, January 24, 2000; 160(2): 165 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V M Miller Gender and vascular reactivity Lupus, June 1, 1999; 8(5): 409 - 415. [Abstract] [PDF]
|
|
|
|
|
|
J. A. McCrohon, W. Jessup, D. J. Handelsman, and D. S. Celermajer Androgen Exposure Increases Human Monocyte Adhesion to Vascular Endothelium and Endothelial Cell Expression of Vascular Cell Adhesion Molecule-1 Circulation, May 4, 1999; 99(17): 2317 - 2322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. McCredie, J. A. McCrohon, L. Turner, K. A. Griffiths, D. J. Handelsman, and D. S. Celermajer Vascular reactivity is impaired in genetic females taking high-dose androgens J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1331 - 1335. [Abstract] [Full Text] [PDF]
|
|