Table 4. Study Conclusions and Major Limitations.
Abbreviations: FES-RT, functional electrical stimulation resistance training; T, testosterone; TT, testosterone therapy; SCI, spinal cord injury; LTM, lean tissue mass; BMR, basal metabolic rate; REE, resting energy expenditure; HO, heterotopic ossification; GLUT4, glucose transporter type 4; Akt, protein kinase B; CSA, cross-sectional area; FIM, functional independence measure; TBI, traumatic brain injury; QTaVI, QT apex interval variability.
Study | Conclusion | Major Limitations |
Holman et al., 2019 [21] | TT + FES-RT improved muscle size & contractile mechanics in men with SCI compared to TT alone. | Does not include a group of FES-RT alone for additional comparisons. Mean baseline T levels above the cutoff for T deficiency. |
Gorgey et al., 2020 [22] | TT + FES-RT increases muscle hypertrophy in untrained muscles. TT may need to be combined with exercise to induce muscle hypertrophy after SCI. | Does not include a group of FES-RT alone for additional comparisons. Mean baseline T levels above the cutoff for testosterone deficiency. |
Gorgey et al., 2020 [23] | Compared to TT alone, TT + FES-RT in men with chronic SCI increased the enzyme Akt that likely contributes to muscle hypertrophy & increased the enzyme GLUT4 that may improve insulin sensitivity. Low-dose TT may not have a meaningful impact on SCI patients with normal baseline T levels. | Did not significantly increase T levels in TT + FES-RT group & did not measure post-intervention T levels in the TT alone group. Does not include FES-RT alone group. Mean baseline T levels above the cutoff for T deficiency. |
Bauman et al., 2011 [24] | TT improves LTM & energy expenditure in hypogonadal men with chronic SCI without adversely affecting prostate health or metabolic parameters. | Functional improvement not assessed. |
Bauman et al., 2015 [25] | Discontinuation of TT in hypogonadal men with chronic SCI resulted in the return of serum T to baseline with retention of LTM & REE improvement. | Limited sample size & inherent diversity of the study sample limited ability to detect a reduction in fat mass. Functional improvement not assessed. |
Gorgey et al., 2021 [26] | Low-dose TT + weekly FES-RT prevents deconditioning in men with SCI. | Did not account for dietary habits. Knee peak isometric & isokinetic torques were not measured in the no TT group. |
Clark et al., 2008 [27] | TT may improve motor function & strength in men with residual motor function after incomplete SCI but not in men with complete SCI. | Notable baseline difference regarding racial composition & length of stay. Not randomized. The study assumed that a proportion of the comparison group had low T & did not receive TT. |
Ripley et al., 2020 [28] | TT is safe & well tolerated in patients with severe TBI with fewer reported adverse events than in the hypogonadal placebo group. Although there were no significant differences in the rate of recovery, the TT group showed the greatest absolute FIM & grip strength improvement. | A small sample size for analysis design. Difficulty with subject enrollment, leading to unequal sample baseline. The severity of TBI did not allow cognitive function assessment. |
Holman et al., 2021 [29] | TT + FES-RT likely benefits bony & non-contractile soft tissue health below the level of injury in men with SCI. An increase in intermuscular fascia length may represent an expansion of connective tissue to accommodate the increase in muscle size. | Short duration & frequency of exercise training. Did not evaluate trabecular bone in TT alone group. Mean baseline testosterone levels above the cutoff for testosterone deficiency. |
Moore et al., 2016 [30] | TT + FES-RT & TT alone increased muscle size without stimulating the growth of pre-existing HO in 2 men with SCI. | Case series limited to two participants is difficult to generalize. The study duration might be too short to allow changes in bone structure. |
Gorgey et al., 2019 [31] | TT + FES-RT increases BMR & muscle size in men with SCI compared to TT alone. | Does not include a group of FES-RT alone for additional comparisons. Mean baseline T levels above the cutoff for T deficiency. |
La Fountaine et al., 2013 [32] | TT for 12 months in hypogonadal men with chronic SCI improves QTaVI, suggesting a reduction in risk for arrhythmia. | The absence of a matched able-bodied control group limits generalization beyond men with SCI. |