Physiological testosterone replacement and arterial endothelial function in men.
OBJECTIVE
The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long-term physiological androgen replacement therapy, at trough and peak testosterone levels.


METHODS
We recruited nine hypogonadal men (aged 35 +/- 4 years) receiving androgen replacement therapy, each treated with 800 mg testosterone (T) depot preparations every 6 months.


METHODS
Serum lipid and hormone levels and arterial reactivity were measured, prior to (trough T) and 2-4 weeks following testosterone administration (peak T). Each subject therefore served as their own control. Vessel diameter was measured by ultrasound at rest, during reactive hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent response] and after sublingual nitroglycerin (GTN, an endothelium-independent dilator).


RESULTS
Serum T (13 +/- 2 nmvs. 27 +/- 3 nm for trough and peak serum T, respectively, P < 0.001; normal adult male range 11-35 nm), and free T (195 +/- 23 pmvs. 510 +/- 93 pm, P < 0.005) significantly increased following subcutaneous depot T administration, as did serum oestradiol (100 +/- 10 pmvs. 175 +/- 9 pm, P = 0.001; normal adult male range < 250 pm). There was a significant decrease in FMD (3.6 +/- 1.1%vs. 3.0 +/- 0.8%, P < 0.01), but GTN responses were similar (9.5 +/- 0.8%vs. 10.4 +/- 1.0%, P > 0.2). Lipid, blood pressure and vessel diameter measurements were also similar before and after testosterone administration.


CONCLUSIONS
Physiological replacement of testosterone is associated with decreased endothelium-dependent dilatation, in hypogonadal men.
Sader
Mark A
MA
Department of Cardiology, Royal Prince Alfred Hospital, and Department of Medicine, The University of Sydney, Sydney, Australia.
Griffiths
Kaye A
KA
Skilton
Michael R
MR
Wishart
Susan M
SM
Handelsman
David J
DJ
Celermajer
David S
DS
D000328:Adult; D001158:Arteries / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin; D011446:Prospective Studies; D012039:Regional Blood Flow; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D014463:Ultrasonography; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D013739:Testosterone; D004958:Estradiol; D005996:Nitroglycerin