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

J Clin Endocrinol Metab. 2006 May;91(5):1691-7. doi: 10.1210/jc.2005-1398. Epub 2006 Feb 21.

Abstract

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.

MeSH terms

  • Adult
  • Androgens / blood
  • Arteries / physiology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors
  • Forearm / blood supply
  • Hemodynamics / drug effects*
  • Hormone Replacement Therapy*
  • Humans
  • Hypogonadism / drug therapy*
  • Hypogonadism / physiopathology*
  • Male
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitroprusside
  • Regional Blood Flow / drug effects
  • Testosterone / blood
  • Testosterone / therapeutic use*
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilator Agents / pharmacology
  • omega-N-Methylarginine / pharmacology

Substances

  • Androgens
  • Enzyme Inhibitors
  • Vasodilator Agents
  • Nitroprusside
  • omega-N-Methylarginine
  • Testosterone
  • Nitric Oxide Synthase Type III