This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ajayi, A. A. L. Articles by Halushka, P. V. Search for Related Content PubMed PubMed Citation Articles by Ajayi, A. A. L. Articles by Halushka, P. V.

(Circulation. 1995;91:2742-2747.)
© 1995 American Heart Association, Inc.

Articles

Testosterone Increases Human Platelet Thromboxane A₂ Receptor Density and Aggregation Responses

Presented in part at the Clinical Research Meeting, Baltimore, Md, April 29-May 2, 1994, and published in abstract form in Clin Res. 1994;42:252A.

Adesuyi A. L. Ajayi, MD, PhD; Rajesh Mathur, PhD; Perry V. Halushka, PhD, MD

From the Departments of Pharmacology and Medicine (A.A.L.A., P.V.H.), Division of Clinical Pharmacology and Department of Obstetrics and Gynecology (R.M.), Medical University of South Carolina, Charleston.

Background The incidence of thrombotic cardiovascular disease is greater in men than in premenopausal women. Testosterone has been implicated as a significant risk factor for cardiovascular disease and for acute myocardial infarctions and strokes in young male athletes who abuse anabolic steroids. Thromboxane A₂ (TXA₂) is a vasoconstrictor and platelet proaggregatory agent that has been implicated in the pathogenesis of cardiovascular disease. We therefore tested the hypothesis that testosterone regulates the expression of human platelet TXA₂ receptors.

Methods and Results In a double-blind, placebo-controlled, randomized, parallel-group study, we determined the effects of testosterone cypionate 200 mg IM given twice, 2 weeks apart, or saline placebo in 16 healthy men. Platelet TXA₂ receptor density (B_max) and dissociation constant (K_d) were measured by use of the TXA₂ mimetic ¹²⁵I-BOP. Platelet aggregation responses to I-BOP and to thrombin and plasma testosterone concentrations were measured before treatment (pretreatment phase), at 2 and 4 weeks (active phase), and again at 8 weeks (recovery phase). Treatment with testosterone was associated with an increase in the B_max value from 0.95±0.13 to 2.10±0.4 pmol/mg protein (n=9), with a peak effect at 4 weeks (P=.001), returning to baseline by 8 weeks. There was no significant change in B_max values in the saline-treated group. The K_d values were unchanged. Testosterone treatment was associated with a significant increase in the maximum platelet aggregation response to I-BOP (P<.001) at 4 weeks and returned to baseline at 8 weeks. The EC₅₀ values were not significantly changed. Platelet TXA₂ receptor density was positively correlated (r=.56, P<.001, n=32 measurements) with pretreatment (endogenous) plasma testosterone levels (range, 215 to 883 ng/dL) but not K_d.

Conclusions Testosterone regulates the expression of platelet TXA₂ receptors in humans. This may contribute to the thrombogenicity of androgenic steroids.

Key Words: thromboxane • platelets • testosterone • cardiovascular diseases

This article has been cited by other articles:

				K. P. Alexander, A. Y. Chen, L. K. Newby, J. B. Schwartz, R. F. Redberg, J. S. Hochman, M. T. Roe, W. B. Gibler, E. M. Ohman, E. D. Peterson, et al. Sex Differences in Major Bleeding With Glycoprotein IIb/IIIa Inhibitors: Results From the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Initiative Circulation, September 26, 2006; 114(13): 1380 - 1387. [Abstract] [Full Text] [PDF]

				M R Graham, F M Grace, W Boobier, D Hullin, A Kicman, D Cowan, B Davies, and J S Baker Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse Br. J. Sports Med., July 1, 2006; 40(7): 644 - 648. [Abstract] [Full Text] [PDF]

				L. H Cavallari, C. M Helgason, L. D Brace, M. A. Viana, and E. A Nutescu Sex Difference in the Antiplatelet Effect of Aspirin in Patients with Stroke Ann. Pharmacother., May 1, 2006; 40(5): 812 - 817. [Abstract] [Full Text] [PDF]

				A.A.L. Ajayi and P.V. Halushka Castration reduces platelet thromboxane A2 receptor density and aggregability QJM, May 1, 2005; 98(5): 349 - 356. [Abstract] [Full Text] [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. 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. 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]

				J. E Rossouw Hormones, genetic factors, and gender differences in cardiovascular disease Cardiovasc Res, February 15, 2002; 53(3): 550 - 557. [Full Text] [PDF]

				Z. F. Ba, P. Wang, D. J. Koo, D. A. Ornan, K. I. Bland, and I. H. Chaudry Attenuation of Vascular Endothelial Dysfunction by Testosterone Receptor Blockade After Trauma and Hemorrhagic Shock Arch Surg, October 1, 2001; 136(10): 1158 - 1163. [Abstract] [Full Text] [PDF]

				G. Khetawat, N. Faraday, M. L. Nealen, K. V. Vijayan, E. Bolton, S. J. Noga, and P. F. Bray Human megakaryocytes and platelets contain the estrogen receptor beta and androgen receptor (AR): testosterone regulates AR expression Blood, April 1, 2000; 95(7): 2289 - 2296. [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]

				C. M. Webb, J. G. McNeill, C. S. Hayward, D. de Zeigler, and P. Collins Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart Disease Circulation, October 19, 1999; 100(16): 1690 - 1696. [Abstract] [Full Text] [PDF]

				S. Narumiya, Y. Sugimoto, and F. Ushikubi Prostanoid Receptors: Structures, Properties, and Functions Physiol Rev, October 1, 1999; 79(4): 1193 - 1226. [Abstract] [Full Text] [PDF]

				V M Miller Gender and vascular reactivity Lupus, June 1, 1999; 8(5): 409 - 415. [Abstract] [PDF]

				T. J. K. Toung, R. J. Traystman, P. D. Hurn, and V. M. Miller Estrogen-Mediated Neuroprotection After Experimental Stroke in Male Rats • Editorial Comment Stroke, August 1, 1998; 29(8): 1666 - 1670. [Abstract] [Full Text] [PDF]

				D. E. Remmers, P. Wang, W. G. Cioffi, K. I. Bland, and I. H. Chaudry Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2919 - H2925. [Abstract] [Full Text] [PDF]

				L. L. Jeppesen, H. S. Jorgensen, H. Nakayama, H. O. Raaschou, T. S. Olsen, and K. Winther Decreased Serum Testosterone in Men With Acute Ischemic Stroke Arterioscler. Thromb. Vasc. Biol., June 1, 1996; 16(6): 749 - 754. [Abstract] [Full Text]

				D. Pratico and G. A. FitzGerald Testosterone and Thromboxane : Of Muscles, Mice, and Men Circulation, June 1, 1995; 91(11): 2694 - 2698. [Full Text]