Oestradiol improves arterial endothelial function in healthy men receivingtestosterone

OBJECTIVE To assess prospectively the effects of low dose oestradiol on art erial endothelial and smooth muscle function in healthy men. Oestrogen use is associated with reduced cardiovascular disease in oestrogen-deficient wo men, however, the vascular effects of low-dose oestradiol in healthy men ha ve not been investigated previously. PATIENTS and DESIGN Twenty-three men (aged 32 +/- 8 years) were randomized to receive depot implants of testosterone (T) alone (group 1, n = 10), or T with either 10 mg (group 2, n = 7) or 20 mg (group 3, n = 6) of oestradiol (E). MEASUREMENTS Hormone levels, lipids and vascu-lar reactivity were measured before, 1 month and 6 months after hormone implantation. Using high-resolut ion ultrasound, brachial artery diameter was measured at rest, during react ive hyperaemia (leading to flow-mediated dilatation, FMD, which is endothel ium-dependent) and after sublingual nitroglycerin (GTN, an endothelium-inde pendent dilator). RESULTS Oestradiol produced a dose-dependent increase in plasma oestradiol (at 1 month 96 +/- 7, 149 +/- 6, 192 +/- 23 pmol/l in the 3 groups, respec- tively, P < 0.001 by anova for trend). Minor side-effects (gynaecomastia, n ipple tenderness) indicated that 20 mg oestradiol was the maximum tolerated dose. There was also a dose-dependent increase in FMD with oestradiol dose : at 1 month, - 0.2, + 0.2 and + 1.8% for groups 1-3, respectively (P = 0.3 1 by anova for trend); and at 6 months, - 0.8, + 0.4 and + 2.2% (P = 0.02). The rise in oestradiol levels following treatment correlated with the impr ovement in FMD (P = 0.01). GTN responses were similar in the 3 groups throu ghout the study. CONCLUSION In healthy young men, oestradiol supplementation is associated w ith enhanced arterial endothelial function, a key marker of vascular health .