Although the Endocrine Society defines hypogonadism as T levels below 300ng/dL, we chose to stratify our subjects by tertiles to evenly stratify our data. Testosterone has been shown to induce mitochondrial biogenesis in rats, as well as increase the expression of peroxisome proliferator-activated receptor-c coactivator-1a, ATP5B and Cox4 in skeletal muscle . The findings remained significant even after adjustment for obesity as determined by BMI and waist to hip ratio among men with different T-levels . TRT may be beneficial in hypogonadal men with SCI as evident by decreasing accumulation of fat mass, VATCSA and thigh % IMF. A decrease in serum T may impair lipoprotein lipases’ action resulting in an increase in VAT. One hypothesis is that serum T and adiposity may be linked through the hypogonadism-obesity-adipocytokine cycle . A recent case report supports the hypothesis that TRT invokes skeletal muscle hypertrophy without the use of exercise intervention . Detailed information on the study design and collected data can be found elsewhere . In addition, the SwiSCI biobank provides a platform for conducting research within the Inception Cohort of SwiSCI by cryopreserving serum, plasma, and peripheral blood mononuclear cells (PBMC), RNA, DNA and urine for research purposes. Study participants were involved in interdisciplinary rehabilitation approach tailored to person’s specific needs and aimed to optimize one’s functioning. Further, despite important physiological role of androgens in females, studies in women are uncommon 22,23. Furthermore, testosterone replacement therapy has shown promise in reducing pain levels and improving quality of life for those suffering from chronic disc-related pain. Cross-sectional1–3 and longitudinal studies4–6 have demonstrated that the concentration levels of total and free serum testosterone (T) decline with increasing age in able-bodied men. Using DXA and MRI measures of body composition, men with lower serum T levels have more total body fat mass, and greater VATCSA when compared to the participants with high serum T. Testosterone replacement therapy (TRT) can help improve muscle mass, increase bone density, and support better overall physical function. This happens because testosterone helps maintain strong muscles, healthy bones, and stable posture. While TRT may improve energy, muscle mass, mood, and bone health, it also carries certain risks. Back pain can come from muscles, bones, nerves, discs, joints, posture, or inflammation. While low testosterone can play a role in muscle weakness, poor posture, and bone loss, it is only one of many possible causes. Even though TRT supports muscles and bones, it is not considered a direct back pain treatment. While bone density improvements usually take months to years to develop, they may help lower the risk of painful bone problems later in life. Proper posture reduces the stress on the spine and helps distribute weight more evenly across the back muscles. Stronger muscles help support the spine better, reducing the load and strain on the back. Testosterone is a critical hormone for muscle development and maintenance. Improved mobility can lead to a more active lifestyle, which is crucial for maintaining overall health and well-being. With reduced pain, individuals often find it easier to move around, bend, and perform tasks that were previously challenging. Back pain can severely limit one's ability to move and perform daily activities. In the short term, patients may begin to notice a reduction in pain and an increase in mobility within a few weeks of starting testosterone therapy. The outcomes of testosterone therapy for back pain can vary depending on the individual and the severity of their condition. This increase in muscle mass helps support the skeletal structure, reducing the load on the spine and decreasing back pain. Testosterone, a hormone produced mainly in the testicles in men and in smaller amounts in the ovaries in women, plays a crucial role in muscle and bone health. In the 70+ years since these findings, we are aware of only two small prospective clinical trials that assessed musculoskeletal or body composition responses to TRT in men with SCI (34, 35), both being open-label, non-placebo-controlled studies. In the 1950s, Cooper et al. published two case series demonstrating that high urinary nitrogen excretion, and a negative nitrogen balance persisted for several months after SCI, and that high-dose intramuscular testosterone (50–100 mg/day) mitigated nitrogen excretion and normalized nitrogen balance in this population (59, 60). Baseline demographics, spinal cord injury (SCI) characteristics, and functional status. All participants exhibited low to low–normal total and/or bioavailable testosterone. The participants within each group had similar SCI characteristics (Table 1) and roughly comparable baseline values for outcome measures (Table 2), although KE whole-muscle CSA and KE MVIC were directionally higher in TRT + finasteride vs. vehicle+placebo, as was performance on several baseline physical function assessments. Total testosterone was measured by automated Cobas® electrochemiluminescence analysis (Roche Diagnostics, Indianapolis, IN, United States), a clinical standard in the VA Pathology and Laboratory Medicine Service (PLMS), and was verified via liquid chromatography–tandem mass spectrometry (LC–MS/MS, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, United States). The participant’s legs were strapped together to limit movement due to involuntary muscle spasms, with the non-dominant limb assessed except when metal hardware precluded accurate muscle or bone imaging/analysis. In the absence of adequate studies conducted in patients with SCI, findings from research conducted using aging hypogonadal or low serum T men were incorporated to inform the effectiveness of transdermal TRT for improving body composition parameters. In contrast to studies in elderly men, it is interesting that no measurable effect was detected on FM in persons with SCI.44 This may be due to a reduction in whole-body energy expenditure, caused by paralysis of lower extremity skeletal muscles and mobility being restricted primarily to wheelchair use. A clinical case series of two patients with SCI did not demonstrate any changes in bone cross-sectional area with 16 months of transdermal TRT.70 Currently, no studies of TRT in any population have been big enough to demonstrate reduced fracture risk. In addition to its impact on LBM and FM, TRT has also been shown to improve bone mass and BMD.60–63 However, the majority of studies looking at the impact of TRT on BMD used intramuscular injections, which is outside the scope of this mini-review. 5 Weighted arithmetic mean calculated from data provided, whereby participants TRT dose was increased and decreased to attain serum T levels within the normal range and below safe limits, respectively. 4 Weighted arithmetic mean calculated from data provided, whereby participants TRT dose was increased and decreased to attain serum T levels within the normal range and below safe limits, respectively.
