Testosterone in DMD follow-up study
Research type
Research Study
Full title
Long term observational extension study of gonadal function after pubertal induction in Duchenne Muscular Dystrophy
IRAS ID
254654
Contact name
Volker Straub
Contact email
Sponsor organisation
Newcastle Joint Research Office
Duration of Study in the UK
2 years, 0 months, 31 days
Research summary
Summary of Research
This is a single centre observational study that aims to follow the progress of 15 adolescents with Duchenne Muscular Dystrophy who were treated for delayed puberty during a previous study entitled, "Observational study of clinical outcomes for testosterone treatment of pubertal delay in Duchenne Muscular Dystrophy." All participants were treated with the standard stepwise regimen of testosterone injections every 4 weeks for 2 years. The follow-up study will start 1 year after their last injection and data will be collected to help us determine whether they have an ongoing requirement for testosterone supplementation. We will use the data to explore the longer-term effects of testosterone on gonadal function, growth, muscle strength and function, bone mineral density and body composition and characterise any side effects of their previous treatment. The study will last for 24 months in total for each participant. It is important to do this study because we do not know what happens to testosterone levels after induction of puberty in Duchenne muscular dystrophy, particularly those who remain on steroids and so this information will be very important to inform future clinical care.
Summary of final report
The aim of this project was to determine the long-term outcome after a 2-year treatment programme using 4-weekly testosterone injections given to start puberty in 15 prepubertal males with DMD. They were treated with a gradually increasing dose of testosterone for 2 years (see Clinical trial NCT02571205). Testosterone (T) is the main male sex hormone. They were reviewed at 6 months after their last injection and then attended a final follow-up visit at around 3 years after their final injection. Participants were an average of 18 years old at final follow-up and had also been on steroids for an average of 11 years. At the end of the 2-year programme, 7/15 patients were still able to walk, a further 3 lost the ability to walk by final visit. Average testosterone levels were similar both at 6 months after the last injection and final follow-up 3 years later. 2/15 patients had restarted testosterone supplementation during clinic visits in the follow-up period. Testicular volume (which correlates well with the body's own testosterone production) significantly increased from the end of pubertal induction to final follow-up. Testosterone levels and testicular volumes, however remain lower than adult reference values. Given the known extra advantages of testosterone on bone health, mood and muscle it will be important to continue to monitor T levels and supplement as required. A significant increase in a hormone called Inhibin B levels occurred from start of T treatment to final visit again but levels remain lower than adult reference values. Inhibin B levels have been shown to be related to sperm production and fertility and so the increase seen here is promising with respect to future fertility but further research is required.
The muscle MRI data demonstrates a clear deterioration in muscle health once T was stopped, with an increases in the amount of fat seen infiltrating the muscle and either no change or small reductions in the area of the muscle leading to overall reductions in the 'functional muscle' area. The MRI findings in this study highlight the importance of prompt T treatment to treat pubertal delay in DMD as the muscle area increased in the original study and has now decreased once it has been stopped. We plan to carry out further work in this area.REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
19/NE/0209
Date of REC Opinion
8 Aug 2019
REC opinion
Further Information Favourable Opinion