Effects Of Different Levels Of Testosterone On Coagulative And Fibrinolytic System

BackgroundEpidemiologic investigations showed that male gender maybe one of the risk factors for arteriosclerosis and that the evidence has accumulated over the past several decades which associates androgenic-anabolic steroid (AAS) use with sudden cardiac death, myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy in humans who habitually use these drugs. People then thought that androgen was unfavorable for the protection of heart vessels. But recent studies also showed that hypotestosteronemia was associated with myocardial infarction (MI) and its risk factors. Testosterone and free testosterone correlated negatively with the degree of coronary artery disease after controlling for age and body mass index. Therefore hypotestosteronemia may be a risk factor for coronary arteriosclerosis in men. Up to now, the studies on the relationship between androgen deficiency and coagulative and fibrinolytic system are very fewer.The first partObjectiveTo detect the effects of castration and different levels of exogenous testosterone undecanoate supplement on coagulative and fibrinolytic system in New Zealand male white rabbits.Methods35 male New Zealand white rabbits were randomized to castration groups and sham operation group after fed with cholesterol rich diet. The castration groups were then randomized to for 4 groups: controlled group, hypotestosteronemia group, physiotestosteronemia group and hypertestosteronemia group. From the 2nd week to 10th week after castration, the later three castration groups were injected testosterone undecanoate (TU) 3mg/kg, 6mg/kg, and 12mg/kg intramuscularly once every two weeks respectively. The sham operation group and the controlled group were injected sterile water intramuscularly at the same time. Blood specimens were collected for three times: before castration, 2nd week after castration, 10th week after castration. All specimens were tested levels of total testosterone (TT), estradiol (E2), blood prothrombin time (PT), activated partial thromboplastin time (APTT) , fibrinogen (FIB) , D-dimers (DD), ADP activity, antithrombin III (AT-III) activity, plasminogen (PLG) and alpha 2-anti plasmin (alpha 2-PI) activity . All rabbits were fed with cholesterol rich diet during the entire periods.ResultsTT decreased significantly after castration, E2 also decreased slightly, E2/TT elevated significantly. TT, EI elevated after TU supplement. The elevating values were proportional to the doses of TU supplement. E2/TT decreased significantly accordingly after TU supplement..After castration, PT, APTT significantly shorten; FIB, DD levels elevated significantly; ADP, PLG and a 2-PI activity increased significantly.After TU supplement, TT, APTT, DD, PLG activity had no significant changes in both hypotestosteronemia and hypertestosteronemia compared with castration groups, FIB decreased slightly in hypotestosteronemia group but significantly inhypertestosteronemia group, ADP activity decreased marketedly in hypotestosteronemia group but didn't in hypertestersteronemia group, AT-III activity and FDP levels didn't change after castration and in hypotestosteronemia group, but both of them elevated in hypertestosteronemia group, a 2-PI activity didn't change in hypotestosteronemia group, but decreased in hypertestosteronemia group. All of the parameters above restored to normal levels in physiotestosteronemia group.ConclusionsCastration and different doses of exogenous TU supplement in male rabbits could result in different severe disorders of sex hormones; Hypotestosteronemia and hypertestosteronemia could all resulted in increasing of coagulative activity.Androgen deficiency could inhibit the activity of fibrinolytic system characterized by increase of a 2-PI activity, but hypertestosteronemia increased the activity of fibrinolytic system characterized by increase of t-PA antigen levels and decrease of a 2-PI activity, anticoagulating factor AT-III activity increased in hypertestosteronemia group.Physiologic dose of exogenous TU supplement could co...