ESPE Abstracts

Introduction: Pharmacological doses of glucocorticoids (GC) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause almost universal pubertal delay. Long term consequences of GC on androgen status in young men who have received testosterone for pubertal induction remain unknown.

Objective: To determine the longer-term outcome after a 2-year pubertal induction regimen using 4-weekly testosterone injections on androgen status.

Design: 15 prepubertal GC-treated males with DMD, who were aged 12-17 years, were treated with an incremental testosterone regimen for 2 years (NCT02571205). They were evaluated at 6 months after last injection and subsequently attended a final follow-up visit, at a mean of 2.8 years (SD 0.44) after final injection. Data collected included testicular volume, testosterone, gonadotrophin and Inhibin B levels. Paired t-tests were used to assess differences pre and post-treatment.

Results: Participants were 18.7 years (SD 1.8) at final follow-up and had been on GC for 11.2 years (SD 2.2). Nine participants were on daily deflazacort, 6 on daily prednisolone. At the time of last injection, 7/15 participants were still ambulant, by final visit only 4 remained ambulant. Mean testosterone levels were similar at 6 months after the last injection and final follow-up (8.6nmol/l (SD 3.4) vs 11.0 nmol/l (SD 6.1). Two of the 15 patients had restarted testosterone supplementation during the follow-up period, based on clinical assessment during routine clinic visits. Testicular volume significantly increased from 2.8 mls (SD 0.9) at end of pubertal induction to 7.1 mls (SD 1.8) at 6-months after and 10.6 mls (SD 3.5) at final follow-up (P<0.001 for difference between end of regimen and final follow-up). In keeping with this, gonadotrophins remained suppressed at the end of pubertal induction but were measurable thereafter. A significant increase in Inhibin B levels occurred from initiation of testosterone treatment to final visit (55.6 pg/ml (SD 47.0) to 158.2 pg/ml (SD 87.6), P=0.004) but final levels remain lower than reference values of mean 305 pg/mL.

Conclusion: Inhibin B levels have been shown to positively correlate with spermatogenesis and the increase seen in this cohort is promising with respect to future fertility. Testosterone levels and testicular volumes, however, remain lower than adult reference values. Given the known additional advantages of testosterone on bone health, muscle and wellbeing, it will be important to continue monitoring testosterone levels in this population and supplement as required if levels become sub-optimal.