Bone metabolism and body composition in Japanese patients with active acromegaly

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 vascular 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, respectively, 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.