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(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

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