OBJECTIVE: To assess the vascular effects of high-dose androgen treatment in genetic females. BACKGROUND: Male gender is an independent risk factor for coronary artery disease, suggesting either a protective effect of estrogens and/or a deleterious effect of androgens. We have recently demonstrated that androgen deprivation is associated with enhanced vascular reactivity in adult men, however, the effects of androgen excess on vascular function in humans has not been reported previously. METHODS: We studied vascular reactivity in two groups of genetic females: 12 female-to-male transsexuals receiving long-term high-dose androgens, and 12 healthy female control subjects, matched for age and smoking history. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (leading to flow-mediated dilatation [FMD], which depends on normal endothelial function) and after sublingual nitroglycerin (NTG), an endothelium-independent dilator. RESULTS: Testosterone levels were higher (15.2+/-8.7 vs. 1.9+/-1.3 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels were lower (1.2+/-0.2 vs. 1.6+/-0.4 mmol/L, p=0.02) in the transsexuals compared with the control subjects. In each group, nine of 12 subjects were current or ex-smokers, leading to impaired FMD in both groups (5.1+/-3.7% in the transsexuals vs. 6.9+/-4.1% in controls, p=0.28). The NTG response was significantly decreased in the transsexuals (15.9+/-4.9% vs. 22+/-5.8% in controls, p=0.01), independent of the effects of age, cholesterol or vessel size. CONCLUSIONS: Long-term treatment with high-dose androgens is associated with impaired vascular reactivity in genetic females, consistent with a deleterious effect of androgen excess on arterial physiology.
OBJECTIVE: To assess the vascular effects of high-dose androgen treatment in genetic females. BACKGROUND: Male gender is an independent risk factor for coronary artery disease, suggesting either a protective effect of estrogens and/or a deleterious effect of androgens. We have recently demonstrated that androgen deprivation is associated with enhanced vascular reactivity in adult men, however, the effects of androgen excess on vascular function in humans has not been reported previously. METHODS: We studied vascular reactivity in two groups of genetic females: 12 female-to-male transsexuals receiving long-term high-dose androgens, and 12 healthy female control subjects, matched for age and smoking history. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (leading to flow-mediated dilatation [FMD], which depends on normal endothelial function) and after sublingual nitroglycerin (NTG), an endothelium-independent dilator. RESULTS:Testosterone levels were higher (15.2+/-8.7 vs. 1.9+/-1.3 mmol/L, p < 0.001) and high-density lipoprotein cholesterol levels were lower (1.2+/-0.2 vs. 1.6+/-0.4 mmol/L, p=0.02) in the transsexuals compared with the control subjects. In each group, nine of 12 subjects were current or ex-smokers, leading to impaired FMD in both groups (5.1+/-3.7% in the transsexuals vs. 6.9+/-4.1% in controls, p=0.28). The NTG response was significantly decreased in the transsexuals (15.9+/-4.9% vs. 22+/-5.8% in controls, p=0.01), independent of the effects of age, cholesterol or vessel size. CONCLUSIONS: Long-term treatment with high-dose androgens is associated with impaired vascular reactivity in genetic females, consistent with a deleterious effect of androgen excess on arterial physiology.
Authors: Stephen L Archer; Ferrante S Gragasin; Linda Webster; Derek Bochinski; Evangelos D Michelakis Journal: Drugs Aging Date: 2005 Impact factor: 3.923