Inclusion Criteria:

• Veterans eligible for care within the Veterans Health Administration (VHA)

• Diagnosis of motor incomplete SCI (AIS C-D) for >24-months involving spinal segment L1 or above from trauma, vascular, or orthopedic pathology

• Low total testosterone (<300 ng/dL) and/or low free testosterone (<4.6 ng/dL)

• Presence of one or more sign of low testosterone, defined as:

  • decreased energy
  • motivation
  • initiative or self-confidence
  • increased fatigue or tiredness
  • reduced sexual desire or activity
  • decreased spontaneous (e.g., morning) erections or erectile dysfunction
  • loss of body hair or reduced shaving
  • feeling sad or blue or having a depressed mood or a persistent low-grade depressive disorder (defined as a score of >3 on the Patient Health Questionnaire [PHQ]-2)
  • hot flashes
  • fatigue or irritability
  • poor concentration or memory
  • mild unexplained (normocytic-normochromic) anemia, defined as HCT <40%, hemoglobin <13.6 g/dL, or red blood cell count <4.5 million/mcL
  • sleep disturbances or increased sleepiness
  • reduced muscle bulk, strength, or physical function
  • increased body fat or body mass index

• Presence of motor impairment, defined as self-selected walking pace ≤1.0 m/s on a 10-meter walk test (10mWT), with or without gait devices or braces and with or without assistance from another person, or as self-selected walking pace >1.0 m/s with reliance on a gait device or brace or with highly compensated movement impairment identified by a trained observer

• Medically stable condition asymptomatic for bladder infection, major decubiti, cardiopulmonary disease, or other significant condition that will interfere with the study

• Documented approval from a physician verifying medical status

Exclusion Criteria:

• Involvement in another research study that may influence outcomes

• Mental state that precludes understanding the protocol

• Life expectancy <12 months

• History of or current congenital SCI (e.g., Chiari malformation, myelomeningocele, intraspinal neoplasm, Friedreich's ataxia) or degenerative spinal disorder (e.g., spinocerebellar degeneration) that may complicate procedures

• Amyotrophic lateral sclerosis, multiple sclerosis, or other neurologic injury / impairment that may complicate procedures

• Current cancer diagnosis

• History of prostate or breast cancer

• Any diagnosed or treated cancer in the past 24 months, except basal or squamous cell carcinoma of the skin that has been successfully treated

• Any major lower-limb fracture in the past 12 months

• Unevaluated circulating PSA >4.0 ng/mL or >3.0 ng/mL in men with prostate cancer risk factors, including agent orange exposure, first degree relative with prostate cancer, or African American background

• Currently seeking fertility or expected during the study

• Diagnosed gynecomastia

• HCT >48%

• Any major cardiovascular event in the last 6 months, defined as:

  • an acute myocardial infarction
  • any cardiac revascularization procedure including stenting
  • angioplasty or coronary artery bypass grafting
  • revascularization of the carotid or middle cerebral artery or procedure to treat critical limb ischemia
  • hospitalization due to unstable angina
  • transient ischemic attack
  • stroke
  • peripheral vascular disease

• Any angina that is not controlled on a current medical regimen (Canadian class II, III, or IV)

• Poorly compensated congestive heart failure (New York Heart Association [NYHA] class III or IV)

• Poorly controlled hypertension when on medication (consistent systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg)

• Poorly controlled arrhythmia of any type

• Severe valvular heart disease

• Baseline electrocardiogram findings such as left bundle branch block or marked abnormality that precludes serial screening for occult ischemic events

• History of unprovoked deep venous thrombosis, unprovoked pulmonary embolism, history of recurrent deep venous thrombosis or known thrombophilia

• Major non-cardiovascular surgery (e.g., major abdominal or thoracic procedure) within 90 days before screening or a major surgery scheduled at the time of screening

• Liver enzymes (AST or ALT) >1.5 times the normal upper limit

• Severe or end-stage chronic kidney disease defined as eGFR <30 mL/min

• Diagnosed, but untreated severe obstructive sleep apnea

• Use of an agent that alters sex-steroid metabolism in the past 90 days, such as: TRT, compounded or over-the-counter androgenic hormone or androgen precursor, 5AR inhibitors, growth hormone, clomiphene, aromatase inhibitors, anti-estrogen or estrogen treatment, or others

• Use of anti-resorptive or bone anabolic drug therapy in the past 180 days

• Acute use (>5 days) of any opioid (e.g., oxycodone, hydrocodone) or systemic glucocorticoids >7.5 mg/d prednisone equivalent (e.g., hydrocortisone 30 mg, methylprednisolone 6 mg, or dexamethasone 1.2 mg) in the week before screening, except for men who are taking these for a chronic condition and who are anticipated to continue these for the study duration

• Known allergy to any TRT component (e.g., cottonseed oil or other)

• Any other condition, lab abnormality, therapy, medical or psychiatric condition, or reason that might pose a risk to the participant, make participation not in the person's best interest, confound the study results (e.g., inability to comply with study requirements), make the participant unsuitable to receive a study intervention, or interfere with their ability to participate for the full study duration