Cargando…

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 seve...

Descripción completa

Detalles Bibliográficos
Autores principales: Francomano, D., Fattorini, G., Gianfrilli, D., Paoli, D., Sgrò, P., Radicioni, A., Romanelli, F., Di Luigi, L., Gandini, L., Lenzi, A., Aversa, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761016/
https://www.ncbi.nlm.nih.gov/pubmed/26162521
http://dx.doi.org/10.1007/s40618-015-0325-4
_version_ 1782416926662721536
author Francomano, D.
Fattorini, G.
Gianfrilli, D.
Paoli, D.
Sgrò, P.
Radicioni, A.
Romanelli, F.
Di Luigi, L.
Gandini, L.
Lenzi, A.
Aversa, A.
author_facet Francomano, D.
Fattorini, G.
Gianfrilli, D.
Paoli, D.
Sgrò, P.
Radicioni, A.
Romanelli, F.
Di Luigi, L.
Gandini, L.
Lenzi, A.
Aversa, A.
author_sort Francomano, D.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4761016
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-47610162016-03-01 Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study Francomano, D. Fattorini, G. Gianfrilli, D. Paoli, D. Sgrò, P. Radicioni, A. Romanelli, F. Di Luigi, L. Gandini, L. Lenzi, A. Aversa, A. J Endocrinol Invest Original Article 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. Springer International Publishing 2015-07-11 2016 /pmc/articles/PMC4761016/ /pubmed/26162521 http://dx.doi.org/10.1007/s40618-015-0325-4 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Francomano, D.
Fattorini, G.
Gianfrilli, D.
Paoli, D.
Sgrò, P.
Radicioni, A.
Romanelli, F.
Di Luigi, L.
Gandini, L.
Lenzi, A.
Aversa, A.
Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
title Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
title_full Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
title_fullStr Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
title_full_unstemmed Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
title_short Acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
title_sort acute endothelial response to testosterone gel administration in men with severe hypogonadism and its relationship to androgen receptor polymorphism: a pilot study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761016/
https://www.ncbi.nlm.nih.gov/pubmed/26162521
http://dx.doi.org/10.1007/s40618-015-0325-4
work_keys_str_mv AT francomanod acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT fattorinig acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT gianfrillid acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT paolid acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT sgrop acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT radicionia acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT romanellif acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT diluigil acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT gandinil acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT lenzia acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy
AT aversaa acuteendothelialresponsetotestosteronegeladministrationinmenwithseverehypogonadismanditsrelationshiptoandrogenreceptorpolymorphismapilotstudy