SUN-LB039 Novel Use of Thromboelastography (TEG) to Investigate the Prothrombotic Effects of Testosterone Replacement Therapy (TRT) for Androgen Deficiency (AD) Established with Diagnostic Rigor (DR)

Background Endocrine Society recommends ≥2 low bioavailable (BAT) or free Testosterone (T) levels in the early AM by tandem mass spectroscopy to establish AD with DR. They also advise against TRT with a recent history of vascular events (VEs). Data from our center affirm these recommendations. TRT increased VE risk four-fold without DR versus with DR, and eight-fold with a history of recent VEs versus without, suggesting that inappropriate TRT might provoke VEs in the absence of AD, or with high vascular risk. The etiopathogenesis of VEs on TRT is not understood, nor is it known if TRT induces a prothrombotic state, but two putative mechanisms might be involved. First, T increases platelet receptors for thromboxane A2, a potent vasoconstrictor and platelet aggregant. Second, T is aromatized to estradiol (E2), a potent activator of the clotting cascade, inhibitor of antithrombin III, and platelet aggregant. Objective To determine (a) whether TEG, a clinically validated tool for assessing platelet function and clotting can be used to identify a prothrombotic state during TRT for AD proven with DR, and (b) if changes are related to estradiol levels. Methods Male veterans >18 years of age referred for suspected AD, and with no contraindications to TRT, were recruited for the study. After AD was established according to guidelines, blood samples were drawn for TEG and E2 before TRT initiation and after 3 months of TRT, and the following TEG parameters were assessed: Reaction Time for initial fibrin formation (R), reflecting the clotting cascade, Kinetic Time for fibrin cross linkage (K), reflecting fibrinogen and platelet number, Angle (α), reflecting the speed of clot strengthening, and Maximum Amplitude (MA), reflecting platelet function. Results In 7 subjects (median age 64 [IQR 38,68]), on TRT for 88±5d (Mean±SE), calculated BAT increased from 82±17ng/dl to 143±32ng/dl (p=0.046), but E2 did not change significantly (14.3±2.5 vs 19.6±4.2pg/ml, p=0.4). R increased 17% on TRT compared to before (∆=0.9±0.2min, p=0.012), showing that time to initial fibrin formation was prolonged, while remaining within the normal range. However, there was no significant change in K, α, or MA. ConclusionsOur data, based on the novel use of TEG to study a potentially prothrombotic effect of TRT, show for the first time that TRT inhibits, not activates the kinetics of the enzymatic process of coagulation. In other words, appropriate TRT had no prothrombotic effect in an admittedly small number of patients with AD established with DR. This accords with both the four-fold decrease in VEs we observed earlier on TRT prescribed appropriately with DR, as well as some prior reports of a lower risk of VEs on TRT. It is conceivable that TRT might induce a prothrombotic state when prescribed inappropriately in the absence of AD, given that many studies showing that TRT increases VE risk have not employed DR to establish AD conclusively. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.