Testosterone and Long-Pulse-Width Stimulation (TLPS) on Denervated Muscles and Cardio-Metabolic Risk Factors After
Ashraf S Gorgey1,2, Refka E Khalil1, Ahmad Alazzam1
1Spinal Cord Injury and Disorders, Central Virginia VA Medical Center, Richmond, VA 23249, USA.
Cells
|December 24, 2025
Summary
Testosterone treatment plus long pulse width stimulation (LPWS) showed modest increases in rectus femoris muscle size in individuals with spinal cord injury (SCI). This approach may help downregulate muscle atrophy genes and improve metabolic health.
Area of Science:
- Neurology
- Muscle Physiology
- Metabolic Health
Background:
- Long pulse width stimulation (LPWS) offers potential for denervated muscle stimulation in spinal cord injury (SCI).
- Investigating testosterone treatment (TT) combined with LPWS to enhance skeletal muscle size, leg lean mass, and metabolic health in SCI individuals with denervation.
Purpose of the Study:
- To evaluate the efficacy of one year of combined TT + LPWS in downregulating muscle atrophy gene expression and upregulating muscle hypertrophy and mitochondrial health in SCI individuals with lower motor neuron (LMN) injury.
Main Methods:
- Ten SCI participants with chronic LMN injury were randomized into two groups for 12 months: TT + LPWS (n=5) or TT + standard neuromuscular electrical stimulation (NMES) (n=5).
- Measurements included body composition (MRI, DXA), metabolic rate, carbohydrate/lipid profiles, and muscle biopsy for gene expression and mitochondrial function.
Main Results:
- A 25% increase in rectus femoris (RF) muscle cross-sectional area (CSA) was observed in the TT + LPWS group after 6 months.
- Trends indicated decreased intramuscular and visceral adipose tissue (VAT) with TT + LPWS.
- TT + LPWS showed a trending decline in muscle atrophy genes (MURF1, FOXO3).
Conclusions:
- Pilot data confirm the safety of LPWS in SCI individuals.
- Six months of TT + LPWS led to modest increases in RF muscle CSA.
- Signaling pathway analysis suggests LPWS downregulates muscle atrophy pathways, warranting further investigation with home-based, more frequent applications.
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