title: Oestradiol improves arterial endothelial function in healthy men receiving testosterone.
abstract: 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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  In healthy young men, oestradiol supplementation is associated with enhanced arterial endothelial function, a key marker of vascular health.
authors.affiliation: Department of Cardiology and Andrology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Sader
authors.forename: R J
authors.initials: RJ
authors.lastname: McCredie
authors.forename: K A
authors.initials: KA
authors.lastname: Griffiths
authors.forename: S M
authors.initials: SM
authors.lastname: Wishart
authors.forename: D J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: D S
authors.initials: DS
authors.lastname: Celermajer
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001916:Brachial Artery / Q000000981:diagnostic imaging; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects*; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D005996:Nitroglycerin; D011446:Prospective Studies; D013739:Testosterone / Q000627:therapeutic use*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents
chemical_list: D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D013739:Testosterone; D004958:Estradiol; D005996:Nitroglycerin