TESTOSTERONE INCREASES HUMAN PLATELET THROMBOXANE A(2) RECEPTOR DENSITY AND AGGREGATION RESPONSES

Background The incidence of thrombotic cardiovascular disease is great er in men than in premenopausal women. Testosterone has been implicate d as a significant risk factor for cardiovascular disease and for acut e myocardial infarctions and strokes in young male athletes who abuse anabolic steroids. Thromboxane A(2) (TXA(2)) is a vasoconstrictor and platelet proaggregatory agent that has been implicated in the pathogen esis of cardiovascular disease. We therefore tested the hypothesis tha t testosterone regulates the expression of human platelet TXA(2) recep tors. Methods and Results In a double-blind, placebo-controlled, rando mized, 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 TXA(2) receptor density (B-max) and dissociat ion constant (K-d) were measured by use of the TXA(2) mimetic I-125-BO P. Platelet aggregation responses to I-BOP and to thrombin and plasma testosterone concentrations were measured before treatment (pretreatme nt phase), at 2 and 4 weeks (active phase), and again at 8 weeks (reco very phase). Treatment with testosterone was associated with an increa se 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 salin e-treated group. The K-d values were unchanged. Testosterone treatment was associated with a significant increase in the maximum platelet ag gregation response to I-BOP (P<.001) at 4 weeks and returned to baseli ne at 8 weeks. The EC(50) values were not significantly changed. Plate let TXA(2) 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 TXA(2) receptors in humans. This may contribute to the thrombogenicity of androgenic steroids.