Oestradiol improves arterial endothelial function in healthy men receiving testosterone

OBJECTIVE To assess prospectively the effects of low dose oestradiol on arterial endothelial and smooth muscle function in healthy men. Oestrogen use is associated with reduced cardiovascular disease in oestrogen-deficient women, however, the vascular effects of low-dose oestradiol in healthy men have 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-resolution ultrasound, brachial artery diameter was measured at rest, during reactive hyperaemia (leading to flow-mediated dilatation, FMD, which is endothelium-dependent) and after sublingual nitroglycerin (GTN, an endothelium-independent 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, nipple 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 = 0·31 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 improvement in FMD (P = 0·01). GTN responses were similar in the 3 groups throughout the study. CONCLUSION In healthy young men, oestradiol supplementation is associated with enhanced arterial endothelial function, a key marker of vascular health.