title: Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study.
abstract: OBJECTIVE
  Testosterone (T) exerts different effects on the cardiovascular system. Despite this knowledge, the acute vascular effect of androgen remains still poorly understood.
  
  
  METHODS
  We investigated the acute effects of T on vascular function in ten men (18-40 years age) with hypogonadism and severe hypotestosteronemia [serum total testosterone (TT) = 0.6 ± 0.3 ng/mL]. In a 4-day double-blind, randomized, placebo-controlled crossover study, we administered 80 mg daily dose of transdermal-T gel (TG) and evaluated endothelial variations with Endopat2000 (reactive hyperemia index, RHI and the augmentation index, AI); also, CAG repeat polymorphism in exon 1 of the androgen receptor gene was investigated.
  
  
  RESULTS
  After TG administration, RHI significantly improved at 4 h (p < 0.05), while AI improvement was recorded at 4 and 96 h, also when adjusted for heart rate (AI@75; p < 0.01 and p < 0.001, respectively). Direct relationships between ΔT, ΔDHT and ΔRHI variations (r = 0.37, p < 0.01; r = 0.17, p < 0.05, respectively) as well as between "CAG repeats" length and ΔLnRHI at 96 h (p < 0.03, r (2) = 0.47) were found. An inverse relationship between ΔT and ΔAI (p < 0.01, r = -0.35) and ΔAI@75 (p < 0.01, r = -0.38) were found.
  
  
  CONCLUSIONS
  Administration of TG causes an acute vasodilation and improves arterial stiffness probably due to non-genomic actions of T. Endothelial vasodilatory response was more pronounced depending on higher plasma TT and DHT levels attained. Clinical implications in elderly frail populations are discussed.
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Francomano
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Fattorini
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Gianfrilli
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Paoli
authors.affiliation: Department of Movement, Human and Health Sciences, University "Foro Italico" of Rome, 00135, Rome, Italy. paolo.sgro@uniroma4.it.
authors.forename: P
authors.initials: P
authors.lastname: Sgrò
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Radicioni
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Romanelli
authors.affiliation: Department of Movement, Human and Health Sciences, University "Foro Italico" of Rome, 00135, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Di Luigi
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gandini
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Department of Experimental Medicine, Endocrinology and Food and Science Section, "Sapienza" University of Rome, 00161, Rome, Italy. antonio.aversa@uniroma1.it.
authors.forename: A
authors.initials: A
authors.lastname: Aversa
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000008:administration & dosage / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011944:Receptors, Androgen / Q000235:genetics*; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood; D018911:Trinucleotide Repeats / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult
chemical_list: C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen; D013739:Testosterone
keywords: CAG repeat; Cardiovascular; Male hypogonadism; Reactive hyperemia index; Treatment