Facioscapulohumeral muscular dystrophy (FSHD) is a common type of adult-onset muscular dystrophy. It is characterized by progressive muscle weakness and atrophy. It may lead to functional decline, impaired ambulation, and decreased quality of life. Currently, there are no approved treatments to reverse or prevent muscle weakness or impairment in FSHD. In healthy individuals, combined administration of human growth hormone (HGH) and Testosterone can improve strength, lean body mass (LBM), and respiratory function. However, this method has not been evaluated in the muscular dystrophy population.
The aim of this study was to assess the tolerability, safety, and exploratory efficacy of the combination treatment of recombinant human growth hormone (rHGH) and testosterone in adult males with FSHD. Twenty men aged 18 to 65 years with genetically confirmed or suspected FSHD type 1 were enrolled from the National Registry of Myotonic Dystrophy and FSHD and the University of Rochester Medical Center between 2018 and 2022. Eligible participants were required to be ambulatory with measurable weakness, able to walk for 6 minutes, and free of other comorbidities like active cancer, cardiovascular disease, and diabetes. Exclusion criteria included obesity (body mass index [BMI] > 35 kg/m²), earlier pituitary disease, severe sleep apnea, or current usage of HGH or testosterone. Participants received intramuscular testosterone enanthate and rHGH for 24 weeks, followed by a 12-week washout period. Compliance was evaluated using medication logs, serial hormone measurements, and returned study supplies. Safety was monitored independently, with pre-specified thresholds (testosterone >1100 ng/dL, hematocrit ≥54%) requiring dose adjustments.
The primary focus was safety and tolerability. Secondary exploratory endpoints included changes in LBM, fat mass, strength, ambulation, function, patient-reported disease burden, fatigue, mood, and sleep. A binomial test was used to evaluate tolerability with a true tolerability rate of 92% at a significance level of 3.6%. Biomarker and functional outcomes were analyzed by mixed-model repeated measures with confidence intervals (CI) and p-values calculated at 0.05.
Of the 20 enrolled participants, 19 completed the study. One withdrew after baseline because of coronavirus disease 2019 (COVID-19)-related concerns and logistical issues. Of 100 expected study visits, 94 were completed. No serious adverse events occurred, and no participant discontinued treatment because of adverse effects. The most common adverse event was a mild injection site reaction (35%). Dose adjustments were required in several cases; one participant required a reduction of both rHGH and testosterone because of elevated hematocrit, five required rHGH dose reduction for elevated IGF-1 (n=3), glycosuria (n=1), or elevated HbA1c (n=1), and one required testosterone dose reduction because of supratherapeutic testosterone levels. All laboratory abnormalities resolved with dose modification.
Exploratory outcomes demonstrated significant improvements at 24 weeks. LBM increased by 2.21 kg (95% CI: 1.35 to 3.07, p < 0.0001). Fat mass decreased by 1.30 kg (95% CI: –2.56 to –0.04, p = 0.04). Functional capacity improved with a mean 6-minute walk distance increase of 37.3 m (95% CI: 18.3 to 56.9, p = 0.001). FSHD composite outcome measure scores improved by 2.4 points (95% CI: –4.0 to –0.8, p = 0.006). Strength gains were observed with a 3% increase in composite quantitative muscle testing (95% CI: 0.3 to 5.6, p = 0.03) and a 0.13-point increase in lower extremity manual muscle testing (MMT) (95% CI: 0.05 to 0.22, p = 0.004). Patient-reported disease burden (FSHD-health index) decreased by 6.1 points (95% CI: –12.0 to –0.2, p = 0.04). Improvements in ambulation, strength, and disease burden persisted, though partially attenuated, during the 12-week washout period.
This study found that testosterone in combination with rHGH was safe and well-tolerated, resulting in significant improvement in muscle mass, strength, ambulation, quality of life, and function in males with FSHD. Limitations included the small sample size, COVID-19-related pandemic adjustments, and an open-label design. Future studies must include females, refine dosing strategies, and employ randomized, placebo-controlled designs to confirm efficacy.
Reference: Heatwole CR, Luebbe E, Hamel J, et al. Study of Testosterone and Recombinant Human Growth Hormone in Facioscapulohumeral Muscular Dystrophy. Neurol Genet. 2025;11(5):e200292. doi:10.1212/NXG.0000000000200292
