THE LANCET 1146 Vol 349 • April 19, 1997 hydrochloride in the treatment of refractory neurocardiogenic syncope in children and adolescents. J Am Coll Cardiol 1994; 24: 490–94. 3 Kosinski DJ, Grubb BP, Elliott L, Dubois D. Treatment of malignant neurogenic syncope with dual chamber cardiac pacing and fluoxetine hydrochloride. PACE 1995; 18: 1455–57. 4 Grubb BP, Kosinski D, Samoil D, Pothoulakis A, Lorton M, Kip K. Postpartum syncope. PACE 1995; 18: 1028–31. 5 McAnally LE, Threlkeld KR, Dreyling CA. Case report of a syncopal episode associated with fluoxetine. Ann Pharm 1992; 26: 1090–91. Cardiovascular Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada (R Sheldon) previously observed in this man. It is possible that a past history of glucose intolerance contributes to the abnormality in endothelium-dependent relaxation. Impaired endothelium- dependent vasorelaxation is an early sign of vascular dysfunction in human beings with hyper-cholesterolaemia. However, in this patient, hypercholesterolaemia was probably not the cause of the lack of flow-dependent (nitric oxide- mediated) vasodilation because plasma concentrations of total and low-density lipoprotein cholesterol, and the ratio of HDL/LDL cholesterol were well within normal range. Absence of a functional oestrogen receptor appears to be associated with intact rapid vascular responsiveness to oestradiol, but impaired flow-mediated endothelium- dependent peripheral vasodilation, and may be a new cardiovascular risk factor in men. We thank Eric Smith (Children’s Hospital Medical Center, Cincinnati, Ohio), Timothy Williams (University of Cincinnati College of Medicine, Ohio), John Kane, Mary Malloy (Cardiovascular Research Institute, University of California, San Francisco), and Linda Hughes (Vascular Laboratory, University of California, San Francisco). 1 Barrett-Connor E, Bush TL. Estrogen and coronary heart disease in Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene Krishnankutty Sudhir, Tony M Chou, Louis M Messina, Stuart J Hutchison, Kenneth S Korach, Kanu Chatterjee, Gabor M Rubanyi Oestrogens protect against cardiovascular disease in women; 1 in men, oestrogens are produced by local tissue aromatisation of androgenic precursors from the testes and adrenal glands. 2 Physiological concentrations of oestrogen have been reported to influence plasma high-density lipoprotein cholesterol in men. 3 It is unclear whether oestrogens influence vascular function in men. We studied the peripheral vasculature of a 31-year-old man, with oestrogen resistance caused by a disruptive mutation in the oestrogen-receptor gene, as previously described. 4 Duplex scanning of the extracranial carotid circulation showed intimal thickening of the common carotid arteries with normal flow velocities. The internal and external carotid arteries were normal, with normal blood-flow velocities. Duplex scanning of the abdominal aorta and iliac arteries showed normal velocities and no evidence of aortic dilation. Leg doppler velocities and ankle-brachial indices were within normal limits. The responses of the brachial artery to vasodilator stimuli were assessed with high-frequency (7·5 MHz) ultrasound. Despite a 120% rise in blood flow velocity after release of 5 min ischaemic cuff occlusion, there was no increase in brachial artery diameter, suggesting absence of detectable flow-mediated endothelium-dependent vasodilation in this artery (figure, top). A 10% increase in diameter of the brachial artery was observed after sublingual nitroglycerin (0·4 mg), indicating normal endothelium-independent vasodilation (figure, middle). This was associated with a 42% increase in brachial artery blood flow velocity. A 10% increase in diameter of the brachial artery was seen after sublingual oestradiol (2 mg), suggesting an intact rapid-vasodilator response to oestradiol. This was associated with a 38% increase in brachial artery blood flow velocity. We were unable to detect any flow-mediated dilation in the brachial artery, an index of endothelium-dependent vasorelaxation. By contrast, in arteries of diameter 6 mm or less, the mean value for flow-mediated vasodilation has been reported as a mean of 10 (SE 2)%, 5 and in normal healthy age- matched men in our laboratory, the mean response is 11 (2)%. Flow-mediated vasodilation in peripheral arteries has been shown to be mediated via release of nitric oxide. The failure of such vasodilation in this patient is likely to be due to impaired peripheral vascular synthesis/release of nitric oxide. The normal response observed to nitroglycerin indicates that the responsiveness of vascular smooth muscle to nitric oxide is preserved in this man. Fasting glucose concentration was normal (5 mmol/L), as was HbA 1C (5·8%), but abnormal glucose tolerance has been 5·6 5·4 5·2 5 4·8 5·6 5·4 5·2 5 4·8 5·6 5·4 5·2 5 4·8 0 2·5 5 7·5 10 0 5 10 15 20 0 5 10 15 Time (min) Hyperaemia Sublingual nitroglycerin Sublingual oestradiol Diameter (mm) Diameter changes recorded from high-frequency ultrasound scans of the brachial artery in a man with oestrogen resistance Top: no change during reactive hyperaemia. Middle: a 10% increase after administration of sublingual nitroglycerin, 0·4 mg. Bottom: a 10% increase after administration of sublingual oestradiol, 2 mg.