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Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?

Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. OBJECTIVE: To assess hypothalamic–pituitary–gonadal axis, muscle vol...

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Autores principales: Wood, Claire L, Hollingsworth, Kieren G, Bokaie, Edrina, Hughes, Eric, Muni-Lofra, Robert, Mayhew, Anna, Mitchell, Rod T, Guglieri, Michela, McElvaney, Joseph, Cheetham, Timothy D, Straub, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620460/
https://www.ncbi.nlm.nih.gov/pubmed/37768006
http://dx.doi.org/10.1530/EC-23-0245
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author Wood, Claire L
Hollingsworth, Kieren G
Bokaie, Edrina
Hughes, Eric
Muni-Lofra, Robert
Mayhew, Anna
Mitchell, Rod T
Guglieri, Michela
McElvaney, Joseph
Cheetham, Timothy D
Straub, Volker
author_facet Wood, Claire L
Hollingsworth, Kieren G
Bokaie, Edrina
Hughes, Eric
Muni-Lofra, Robert
Mayhew, Anna
Mitchell, Rod T
Guglieri, Michela
McElvaney, Joseph
Cheetham, Timothy D
Straub, Volker
author_sort Wood, Claire L
collection PubMed
description Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. OBJECTIVE: To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction. METHODS: A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 years (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI. RESULTS: Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol/L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL (s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL (s.d.87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased. INTERPRETATION: Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.
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spelling pubmed-106204602023-11-03 Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy? Wood, Claire L Hollingsworth, Kieren G Bokaie, Edrina Hughes, Eric Muni-Lofra, Robert Mayhew, Anna Mitchell, Rod T Guglieri, Michela McElvaney, Joseph Cheetham, Timothy D Straub, Volker Endocr Connect Research Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. OBJECTIVE: To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction. METHODS: A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 years (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI. RESULTS: Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol/L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL (s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL (s.d.87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased. INTERPRETATION: Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important. Bioscientifica Ltd 2023-10-26 /pmc/articles/PMC10620460/ /pubmed/37768006 http://dx.doi.org/10.1530/EC-23-0245 Text en © the author(s) https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Research
Wood, Claire L
Hollingsworth, Kieren G
Bokaie, Edrina
Hughes, Eric
Muni-Lofra, Robert
Mayhew, Anna
Mitchell, Rod T
Guglieri, Michela
McElvaney, Joseph
Cheetham, Timothy D
Straub, Volker
Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?
title Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?
title_full Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?
title_fullStr Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?
title_full_unstemmed Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?
title_short Is ongoing testosterone required after pubertal induction in Duchenne muscular dystrophy?
title_sort is ongoing testosterone required after pubertal induction in duchenne muscular dystrophy?
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620460/
https://www.ncbi.nlm.nih.gov/pubmed/37768006
http://dx.doi.org/10.1530/EC-23-0245
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