Vascular reactivity in congenital hypogonadal men before and after testosterone replacement therapy.
BACKGROUND
The contribution of endogenous testosterone (TS) in the functional integrity of peripheral circulation in men was studied.


OBJECTIVE
The objective of this study was to observe vascular reactivity in male congenital hypogonadal patients before and after prolonged exposure to normal TS levels.


METHODS
This was a longitudinal study in which, basically and after 6-month (range, 6-8 months) androgen treatment, we investigated forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (Ach), alone or in the presence of N(G)-monomethyl-l-arginine infusion, and by sodium nitroprusside. We also evaluated, by Doppler ultrasound, flow-mediated dilation of the brachial artery (BA) in response to reactive hyperemia (RH) and glyceryl trinitrate (GTN).


METHODS
The studies were conducted at university referral centers for andrologic and blood pressure diseases.


METHODS
Eight adult male Caucasian hypogonadal patients and nine healthy matched control subjects were studied.


METHODS
Intervention was TS enanthate (250 mg in 1 ml oily solution) by im injection every 3 wk.


RESULTS
At baseline, BA diameter and RH, flow-mediated dilation, and GTN responses showed no difference between the two groups. TS therapy increased plasma total TS (P < 0.02) and reduced high-density lipoprotein (P < 0.01) and total cholesterol (P < 0.04). It did not affect vasodilation to sodium nitroprusside (355 +/- 47%), but it further reduced the vascular response to Ach (187 +/- 29%, P < 0.01 vs. baseline) and abolished the inhibition by N(G)-monomethyl-l-arginine on Ach (inhibition, 3.2%). Moreover, TS therapy decreased (P < 0.01) flow-mediated dilation, whereas it did not modify BA diameter and responses to RH and GTN.


CONCLUSIONS
Hypogonadal patients show impaired vascular reactivity, including endothelial-dependent vasodilation due to reduced nitric oxide availability. TS administration further impairs nitric oxide availability in these patients.
Department of Internal Medicine, Pisa University, Italy. g.bernini@int.med.unipi.it
Giampaolo
G
Bernini
Daniele
D
Versari
Angelica
A
Moretti
Agostino
A
Virdis
Lorenzo
L
Ghiadoni
Michele
M
Bardini
Chiara
C
Taurino
Domenico
D
Canale
Stefano
S
Taddei
Antonio
A
Salvetti
D000328:Adult; D000728:Androgens / Q000097:blood; D001158:Arteries / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects*; D020249:Hormone Replacement Therapy; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009599:Nitroprusside; D012039:Regional Blood Flow / Q000187:drug effects; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000728:Androgens; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D013739:Testosterone; D052250:Nitric Oxide Synthase Type III