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Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort

BACKGROUND: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declin...

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Autores principales: Anand‐Ivell, Ravinder, Heng, Kee, Severn, Katie, Antonio, Leen, Bartfai, Gyorgy, Casanueva, Felipe F., Huhtaniemi, Ilpo T., Giwercman, Aleksander, Maggi, Mario, O'Neill, Terence W., Punab, Margus, Rastrelli, Giulia, Slowikowska‐Hilczer, Jolanta, Tournoy, Jos, Vanderschueren, Dirk, Wu, Frederick C. W., Ivell, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540576/
https://www.ncbi.nlm.nih.gov/pubmed/35770372
http://dx.doi.org/10.1111/andr.13220
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author Anand‐Ivell, Ravinder
Heng, Kee
Severn, Katie
Antonio, Leen
Bartfai, Gyorgy
Casanueva, Felipe F.
Huhtaniemi, Ilpo T.
Giwercman, Aleksander
Maggi, Mario
O'Neill, Terence W.
Punab, Margus
Rastrelli, Giulia
Slowikowska‐Hilczer, Jolanta
Tournoy, Jos
Vanderschueren, Dirk
Wu, Frederick C. W.
Ivell, Richard
author_facet Anand‐Ivell, Ravinder
Heng, Kee
Severn, Katie
Antonio, Leen
Bartfai, Gyorgy
Casanueva, Felipe F.
Huhtaniemi, Ilpo T.
Giwercman, Aleksander
Maggi, Mario
O'Neill, Terence W.
Punab, Margus
Rastrelli, Giulia
Slowikowska‐Hilczer, Jolanta
Tournoy, Jos
Vanderschueren, Dirk
Wu, Frederick C. W.
Ivell, Richard
author_sort Anand‐Ivell, Ravinder
collection PubMed
description BACKGROUND: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell‐produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin‐like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes. OBJECTIVES: To characterize insulin‐like peptide 3 as a biomarker to assess gonadal status in aging men. METHODS AND MATERIALS: A large European multicenter (European Male Aging Study) cohort of community‐dwelling men was analyzed to determine how insulin‐like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters. RESULTS AND DISCUSSION: Insulin‐like peptide 3 declines cross‐sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin‐like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin‐like peptide 3 is negatively dependent on luteinizing hormone and sex hormone‐binding globulin and positively dependent on follicle‐stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin‐like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin‐like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European‐wide reference range for insulin‐like peptide 3 (95% confidence interval) adjusted for increasing age. CONCLUSION: Insulin‐like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin‐dependent short‐term regulation and within‐individual variation in testosterone.
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spelling pubmed-95405762022-10-14 Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort Anand‐Ivell, Ravinder Heng, Kee Severn, Katie Antonio, Leen Bartfai, Gyorgy Casanueva, Felipe F. Huhtaniemi, Ilpo T. Giwercman, Aleksander Maggi, Mario O'Neill, Terence W. Punab, Margus Rastrelli, Giulia Slowikowska‐Hilczer, Jolanta Tournoy, Jos Vanderschueren, Dirk Wu, Frederick C. W. Ivell, Richard Andrology Original Articles BACKGROUND: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing neoplasia, some of which are associated with declining levels of Leydig cell‐produced testosterone. High natural biological variance, together with multiple factors that can modulate circulating testosterone concentration, may influence its interpretation and clinical implications. Insulin‐like peptide 3 is a biomarker of Leydig cell function that might provide complementary information on testicular health and its downstream outcomes. OBJECTIVES: To characterize insulin‐like peptide 3 as a biomarker to assess gonadal status in aging men. METHODS AND MATERIALS: A large European multicenter (European Male Aging Study) cohort of community‐dwelling men was analyzed to determine how insulin‐like peptide 3 relates to a range of hormonal, anthropometric, and lifestyle parameters. RESULTS AND DISCUSSION: Insulin‐like peptide 3 declines cross‐sectionally and longitudinally within individuals at approximately 15% per decade from age 40 years, unlike testosterone (1.9% per decade), which is partly compensated by increasing pituitary luteinizing hormone production. Importantly, lower insulin‐like peptide 3 in younger men appears to persist with aging. Multiple regression analysis shows that, unlike testosterone, insulin‐like peptide 3 is negatively dependent on luteinizing hormone and sex hormone‐binding globulin and positively dependent on follicle‐stimulating hormone, suggesting a different mechanism of gonadotropic regulation. Circulating insulin‐like peptide 3 is negatively associated with increased body mass index or waist circumference and with smoking, and unlike testosterone, it is not affected by weight loss in obese individuals. Geographic variation in mean insulin‐like peptide 3 within Europe appears to be largely explained by differences in these parameters. The results allowed the establishment of a European‐wide reference range for insulin‐like peptide 3 (95% confidence interval) adjusted for increasing age. CONCLUSION: Insulin‐like peptide 3 is a constitutive biomarker of Leydig cell functional capacity and is a robust, reliably measurable peptide not subject to gonadotropin‐dependent short‐term regulation and within‐individual variation in testosterone. John Wiley and Sons Inc. 2022-07-11 2022-10 /pmc/articles/PMC9540576/ /pubmed/35770372 http://dx.doi.org/10.1111/andr.13220 Text en © 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Anand‐Ivell, Ravinder
Heng, Kee
Severn, Katie
Antonio, Leen
Bartfai, Gyorgy
Casanueva, Felipe F.
Huhtaniemi, Ilpo T.
Giwercman, Aleksander
Maggi, Mario
O'Neill, Terence W.
Punab, Margus
Rastrelli, Giulia
Slowikowska‐Hilczer, Jolanta
Tournoy, Jos
Vanderschueren, Dirk
Wu, Frederick C. W.
Ivell, Richard
Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort
title Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort
title_full Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort
title_fullStr Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort
title_full_unstemmed Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort
title_short Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort
title_sort association of age, hormonal, and lifestyle factors with the leydig cell biomarker insl3 in aging men from the european male aging study cohort
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540576/
https://www.ncbi.nlm.nih.gov/pubmed/35770372
http://dx.doi.org/10.1111/andr.13220
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