CLINICAL STUDIES
Vascular reactivity is impaired in genetic females taking high-dose androgens
Robyn J. McCredie, BSc*,
Jane A. McCrohon, MB, BS, FRACP*  ,
Leo Turner, RN ,
Kaye A. Griffiths, DMU* ,
David J. Handelsman, MB, BS, PhD, FRACP  and
David S. Celermajer, MB, BS, PhD, FRACP*
* Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
The Heart Research Institute, Sydney, Australia
Andrology Unit, Royal Prince Alfred Hospital, Sydney, Australia
Department of Medicine, Sydney University, Sydney, Australia
Manuscript received March 20, 1998;
revised manuscript received June 22, 1998,
accepted July 9, 1998.
Address for correspondence: Dr. David S. Celermajer, Medical Foundation Fellow, Department of Cardiology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, 2050 Sydney, Australia
davidc{at}card.rpa.cs.nsw.gov.au
Objective. To assess the vascular effects of high-dose androgen treatment in genetic females.
Background. Male gender is an independent risk factor for coronary artery disease, suggesting either a protective effect of estrogens and/or a deleterious effect of androgens. We have recently demonstrated that androgen deprivation is associated with enhanced vascular reactivity in adult men, however, the effects of androgen excess on vascular function in humans has not been reported previously.
Methods. We studied vascular reactivity in two groups of genetic females: 12 female-to-male transsexuals receiving long-term high-dose androgens, and 12 healthy female control subjects, matched for age and smoking history. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (leading to flow-mediated dilatation [FMD], which depends on normal endothelial function) and after sublingual nitroglycerin (NTG), an endothelium-independent dilator.
Results. Testosterone levels were higher (15.2 ± 8.7 vs. 1.9 ± 1.3 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels were lower (1.2 ± 0.2 vs. 1.6 ± 0.4 mmol/L, p = 0.02) in the transsexuals compared with the control subjects. In each group, nine of 12 subjects were current or ex-smokers, leading to impaired FMD in both groups (5.1 ± 3.7% in the transsexuals vs. 6.9 ± 4.1% in controls, p = 0.28). The NTG response was significantly decreased in the transsexuals (15.9 ± 4.9% vs. 22 ± 5.8% in controls, p = 0.01), independent of the effects of age, cholesterol or vessel size.
Conclusions. Long-term treatment with high-dose androgens is associated with impaired vascular reactivity in genetic females, consistent with a deleterious effect of androgen excess on arterial physiology.
|
Abbreviations and Acronyms
| | FMD | = flow-mediated dilatation | | HDL | = high-density lipoprotein | | NTG | = nitroglycerin |
|
This article has been cited by other articles:
|
|
|
|
 
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning
Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response
Eur. Heart J.,
February 2, 2005;
26(4):
363 - 368.
[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]
|
|
|
|
|
|
|
A. K. Death, K. C. Y. McGrath, M. A. Sader, S. Nakhla, W. Jessup, D. J. Handelsman, and D. S. Celermajer
Dihydrotestosterone Promotes Vascular Cell Adhesion Molecule-1 Expression in Male Human Endothelial Cells via a Nuclear Factor-{kappa}B-Dependent Pathway
Endocrinology,
April 1, 2004;
145(4):
1889 - 1897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kimura, K. Sudhir, M. Jones, E. Simpson, A.-M. Jefferis, and J. P.F. Chin-Dusting
Impaired Acetylcholine-Induced Release of Nitric Oxide in the Aorta of Male Aromatase-Knockout Mice: Regulation of Nitric Oxide Production by Endogenous Sex Hormones in Males
Circ. Res.,
December 12, 2003;
93(12):
1267 - 1271.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
M. A. Cavasin, S. S. Sankey, A.-L. Yu, S. Menon, and X.-P. Yang
Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction
Am J Physiol Heart Circ Physiol,
May 1, 2003;
284(5):
H1560 - H1569.
[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]
|
|
|
|
|
|
|
O. Baltatu, C. Cayla, R. Iliescu, D. Andreev, and M. Bader
Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats
Hypertension,
March 1, 2003;
41(3):
830 - 833.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
G. G. Geary, A. M. McNeill, J. A. Ospina, D. N. Krause, K. S. Korach, and S. P. Duckles
Genome and Hormones: Gender Differences in Physiology: Selected Contribution: Cerebrovascular NOS and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-alpha
J Appl Physiol,
November 1, 2001;
91(5):
2391 - 2399.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Diamanti-Kandarakis, G. Spina, C. Kouli, and I. Migdalis
Increased Endothelin-1 Levels in Women with Polycystic Ovary Syndrome and the Beneficial Effect of Metformin Therapy
J. Clin. Endocrinol. Metab.,
October 1, 2001;
86(10):
4666 - 4673.
[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]
|
|
|
|
|
|
|
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. Vehkavaara, T. Hakala-Ala-Pietila, A. Virkamaki, R. Bergholm, C. Ehnholm, O. Hovatta, M.-R. Taskinen, and H. Yki-Jarvinen
Differential Effects of Oral and Transdermal Estrogen Replacement Therapy on Endothelial Function in Postmenopausal Women
Circulation,
November 28, 2000;
102(22):
2687 - 2693.
[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]
|
|
|
|
|
|
|
V M Miller
Gender and vascular reactivity
Lupus,
June 1, 1999;
8(5):
409 - 415.
[Abstract]
[PDF]
|
|
|
|
