MON-LB050 Preliminary Results from the "Observational Study of Clinical Outcomes for Testosterone Treatment of Pubertal Delay in Duchenne Muscular Dystrophy (DMD) (NCT 02571205)"

Abstract

Delayed puberty is almost universal in patients with Duchenne muscular dystrophy (DMD) treated with pharmacological doses of glucocorticoid. We have demonstrated wide variation in terms of how delayed puberty is managed and set out to evaluate the efficacy of exogenous testosterone on a range of endpoints. This was a single centre clinical trial (NCT02571205) of 15 adolescents with DMD and delayed puberty (12-16 years) treated with an increasing dose of Sustanon 250 starting at 0.2 mls up to a maximum of 1ml every 4 weeks for 2 years. We assessed a range of endpoints including pubertal status, gonadal function, bone turnover markers as well as adverse events (AEs). All 15 patients completed 27 months of follow-up. All were pre-pubertal at baseline with a testicular volume (TV) less than 4mls. Baseline testosterone levels were <2nmol/l. 27 months later (3 months after the last testosterone injection) the mean testicular volume was 3.3 mls (range 1.5-6mls), Tanner stage G4P4 (range G4P4-G5P5) with a mean testosterone of 10.4 nmol/l (1.9-21.8). Mean FSH was 9.1 IU/L (range 1.8-38.3) and mean LH 8.6 IU/L(range <0.5-25.1). By 9-12 months after the last injection there was evidence of endogenous testosterone production with a mean testicular volume of 8mls (4.75-10) and mean testosterone of 11.6nmol/l (5.1-19.1). There were no change in mean P1NP or CTX levels during the study but RANKL decreased from 515.0 pmol/l (227.1) at baseline to 308.2 pmol/l (214.7) after 24 months of testosterone. Qualitative interviews/treatment satisfaction questionnaire responses were encouraging with no significant AEs attributed to testosterone therapy and all patients either ‘satisfied’ or ‘very/extremely satisfied’ with their treatment. 2 patients chose to stop testosterone injections at 18 months because of concerns about potential effects on mobility. They continued to progress through puberty. Testosterone treatment is not part of DMD standard care but this regimen appears to be effective and well-tolerated. By 1 year after cessation of the regimen there is evidence of endogenous testosterone production. Continuing data is required in terms of longer term gonadal function and effects on muscle function and skeletal integrity also require detailed scrutiny. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.