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Vascular Reactivity in Congenital Hypogonadal Men before and after Testosterone Replacement Therapy

Departments of Internal Medicine (G.B., D.V., A.M., A.V., L.G., M.B., C.T., S.T., A.S.) and Endocrinology (D.C.), Pisa University, 56100 Pisa, Italy

Address all correspondence and requests for reprints to: Bernini Giampaolo, M.D., Department of Internal Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy. E-mail: g.bernini{at}int.med.unipi.it.

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.

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