Vascular reactivity in congenital hypogonadal men before and after testosterone replacement therapy

Context: 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. Design: 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). Setting: The studies were conducted at university referral centers for andrologic and blood pressure diseases. Patients: Eight adult male Caucasian hypogonadal patients and nine healthy matched control subjects were studied. Intervention: 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.