LONG-TERM ESTROGEN THERAPY IMPROVES VASCULAR FUNCTION IN MALE TO FEMALE TRANSSEXUALS

Objectives. This study sought to examine the effects of longterm estro gen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal wom en. Background. Gender differences in coronary artery disease have lar gely been attributed to the beneficial effects of estrogen on vascular function and plasma lipids in women. However, the effects of estrogen on the male vasculature have not been widely studied. Methods. We com pared the effects of estrogen on vascular function in 14 male to femal e transsexuals, 14 age-matched men and 15 premenopausal women. Plow-me diated vasodilation and response to nitroglycerin were assessed in the brachial artery using noninvasive ultrasound. Results. Flow-mediated vasodilation was similar in transsexuals and women but greater than th at in men ([mean +/- SE] 11.5 +/- 1.3% and 9.4 +/- 1.1% vs, 5.2 +/- 1. 0% respectively, p < 0.005). Responses to nitroglycerin were also grea ter in transsexuals and women than in men (21.6 +/- 1.7% and 21.0 +/- 0.9% vs. 14.5 +/- 1.2%, respectively, p = 0.0005). These differences p ersisted even after adjusting for vessel size. Despite similar total c holesterol levels, transsexuals had high density lipoprotein cholester ol levels similar to those in women and greater than those observed in men (1.76 +/- 0.12 and 1.82 +/- 0.11 mmol/liter vs. 1.35 +/- 0.07 mmo l/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater in transsexuals than in men and women, and low density lipopro tein cholesterol (LDL-C) particle size was smaller (25.7 +/- 0.2 nm vs . 26.2 +/- 0.1 and 26.6 +/- 0.1 nm, respectively, p = 0.0001), Serum t estosterone (an index of estrogen therapy in transsexuals) was markedl y suppressed in transsexuals and similar to that in women. Univariate analysis revealed that there was a strong inverse correlation between serum testosterone and flow-mediated vasodilation (r(s) = -0.48, p < 0 .005). Multivariate analysis revealed that the best combination of pre dictors of dow-mediated vasodilation was serum testosterone, vessel si ze and LDL-C (R-2 = 0.3, p < 0.005). Conclusions. Long-term estrogen t herapy appears to improve vascular function in male to female transsex uals and occurs despite higher triglyceride levels and the presence of small, dense LDL-C. The beneficial effects of estrogen are not gender specific or solely mediated through endothelium-derived nitric oxide. (C) 1997 by the American College of Cardiology.