Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study

PURPOSE 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. CONCLUSION 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.