Long-term oestrogen therapy is associated with improved endothelium-dependent vasodilation in the forearm resistance circulation of biological males

1. The aim of the present study was to determine the effects of long-term oestrogen on resistance vessel reactivity in biological males. 2. Recent studies have demonstrated that long-term oestrogen therapy favourably alters the lipid profile and improves vasodilator function in the conduit arteries of biological males. Whether a similar benefit is exerted on the resistance circulation is not known. Therefore, we examined the effects of long-term oestrogen therapy on skeletal muscle resistance vessel function in biological males and the potential mechanisms by which it may exert its effects. 3. Forearm blood flow (FBF) and resistance were compared in 15 male-to-female transsexuals being prescribed oestrogen, with 14 age-matched healthy males, at rest and in response to the endothelium-dependent nitric oxide (NO) vasodilator acetylcholine (ACh), the endothelium-independent but NO-mediated vasodilator sodium nitroprusside (SNP), the endothelium-independent and non-NO-mediated vasodilator verapamil (VER) and the endothelium-independent vasoconstrictor phenylephrine (PE). 4. Basal blood flows were similar in the two groups. However, the male-to-female transsexuals had a significant upward and leftward shift in FBF responses to ACh compared with males, with a 52% increase in FBF responses at the highest dose of ACh used. Forearm blood flow in transsexuals rose from a mean (+/- SEM) baseline level of 3.02 +/- 0.25 to a maximum of 19.5 +/- 2.59 mL/min per 100 mL forearm tissue (compared with 3.24 +/- 0.41 and 9.43 +/- 1.97 mL/min per 100 mL forearm tissue, respectively, in males) with the highest dose of ACh (+2.73 micrograms/min per 100 mL; P < 0.0005). Forearm vascular resistance was also significantly reduced in transsexuals compared with males (P < 0.05). Vasodilator responses to SNP, VER and PE were similar in both groups. 5. There were no differences observed in total cholesterol and low-density lipoprotein-cholesterol levels. However, male-to-female transsexuals had 20% higher high-density lipoprotein-cholesterol levels compared with males (1.57 +/- 0.11 vs 1.26 +/- 0.08 mmol/L, respectively; P < 0.05) and 47% higher triglyceride levels (P < 0.005). Serum testosterone levels (an index of oestrogen therapy) was a predictor of responses to endothelium-dependent vasodilation (rs = -0.50; P < 0.01). 6. Long-term oestrogen therapy enhances endothelium-dependent vasodilation in the skeletal muscle microcirculation of biological males. The effects appear to be selective because endothelium-independent vasodilation and vasoconstriction are not altered.