Low testosterone produce hypercoagulable state (Erem 2008)

Sweetland S, Beral V, Balkwill A, Liu B, Benson VS, Canonico M, Green J, Reeves GK; The Million Women Study Collaborators. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost. 2012 Nov;10(11):2277-86.

Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. Background: Current use of menopausal hormone therapy (HT) increases venous thromboembolism (VTE) risk and the formulations used may affect risk. Methods: 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: During 3.3million years of follow-up, 2200 women had an incident VTE, diagnosed 1.5 years, on average, after last reporting HT use. RRs in current versus never users at last reporting varied by HT formulation: risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR=2.07 [95%CI:1.86-2.31] versus 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, HT risk varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] versus 1.91 [1.69-2.17];P(heterogeneity) =0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first two years after starting than later (P(heterogeneity) =0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over five years, 1 in 660 never users of HT were admitted to hospital for (or died from) pulmonary embolism, compared to 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate. Conclusions: VTE risk varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate. PMID: 22963114

Toorians AW, Thomassen MC, Zweegman S, Magdeleyns EJ, Tans G, Gooren LJ, Rosing J. Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people. J Clin Endocrinol Metab. 2003 Dec;88(12):5723-9.

The incidence of venous thrombosis associated with estrogen treatment in male-to-female (M-->F) transsexuals is considerably higher with administration of oral ethinyl estradiol (EE) than with transdermal (td) 17-beta-estradiol (E(2)). To find an explanation for the different thrombotic risks of oral EE and td E(2) use, we compared the effects of treatment of M-->F transsexuals with cyproterone acetate (CPA) only, and with CPA in combination with td E(2), oral EE, or oral E(2) on a number of hemostatic variables [activated protein C (APC) resistance and plasma levels of protein S, protein C, and prothombin], all of which are documented risk factors for venous thrombosis. APC resistance was determined by quantification of the effect of APC on the amount of thrombin generated during tissue factor-initiated coagulation; plasma levels of total and free protein S were determined by standard ELISA; and levels of prothrombin and protein C were determined with functional assays after complete activation of the zymogens with specific snake venom proteases. CPA-only, td-E(2)+CPA, or oral-E(2)+CPA treatment produced rather small effects on hemostatic variables, whereas oral EE treatment resulted in a large increase in APC resistance from 1.2 +/- 0.8 to 4.1 +/- 1 (P < 0.001), a moderate increase in plasma protein C (9%; P = 0.012), and a large decrease in both total and free plasma protein S (30%; P < 0.005). The large differential effect of oral EE and oral E(2) indicates that the prothrombotic effect of EE is due to its molecular structure rather than to a first-pass liver effect (which they share). Moreover, these differences may explain why M-->F transsexuals treated with oral EE are exposed to a higher thrombotic risk than transsexuals treated with td E(2). Testosterone administration to female-to-male transsexuals had an antithrombotic effect.

Trenor CC 3rd, Chung RJ, Michelson AD, Neufeld EJ, Gordon CM, Laufer MR, Emans SJ. Hormonal contraception and thrombotic risk: a multidisciplinary approach. Pediatrics. 2011 Feb;127(2):347-57.

Heightened publicity about hormonal contraception and thrombosis risk and the publication of new guidelines by the World Health Organization in 2009 and the Centers for Disease Control and Prevention in 2010 addressing this complex issue have led to multidisciplinary discussions on the special issues of adolescents cared for at our pediatric hospital. In this review of the literature and new guidelines, we have outlined our approach to the complex patients referred to our center. The relative risk of thrombosis on combined oral contraception is three- to fivefold, whereas the absolute risk for a healthy adolescent on this therapy is only 0.05% per year. This thrombotic risk is affected by estrogen dose, type of progestin, mechanism of delivery, and length of therapy. Oral progestin-only contraceptives and transdermal estradiol used for hormone replacement carry minimal or no thrombotic risk. Transdermal, vaginal, or intrauterine contraceptives and injectable progestins need further study. A personal history of thrombosis, persistent or inherited thrombophilia, and numerous lifestyle choices also influence thrombotic risk. In this summary of one hospital's approach to hormone therapies and thrombosis risk, we review relative-risk data and discuss the application of absolute risk to individual patient counseling. We outline our approach to challenging patients with a history of thrombosis, known thrombophilia, current anticoagulation, or family history of thrombosis or thrombophilia. Our multidisciplinary group has found that knowledge of the guidelines and individualized management plans have been particularly useful for informing discussions about hormonal and nonhormonal options across varied indications. PMID: 21199853

Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May;89(5):2085-98.