Serum testosterone levels may influence body composition and cardiometabolic health in men with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To establish the association between serum testosterone (T) levels, biomarkers of cardiometabolic health and regional body composition variables after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Metabolic and body composition measurements were collected from thirty-six men with chronic motor complete SCI. Serum T, carbohydrate, and lipid profiles were measured after an overnight fast. Body composition was measured using anthropometrics, dual-energy X-ray absorptiometry, and magnetic resonance imaging. Participants were evenly classified into tertiles based on their serum T levels into low, mid-normal and normal ranges. RESULTS: Low, mid-normal, and normal range serum T were 288.8 ± 84.9 ng/dL, 461.0 ± 52.5 ng/dL and 648.0 ± 53.5 ng/dL, respectively. Low range serum T group had greater total (9.6%, P = 0.04) percentage fat mass and visceral adipose tissue (VAT) area (72%, P = 0.01) compared to normal range serum T group. Serum T was related to the absolute whole thigh muscle area (r = 0.40, P < 0.05) after controlling for body mass index. Serum T was negatively related to fasting plasma glucose (r = -0.46, P = 0.006) and insulin (r = -0.42, P = 0.01), HbA1c (r = -0.39, P = 0.02) and triglycerides (r = -0.36, P = 0.03). CONCLUSION: Men with low serum T have more unfavorable body composition and cardiometabolic health outcomes after SCI. Testosterone replacement therapy may serve as a potential strategy in preventing cardiometabolic disorders after SCI.

Body composition changes with testosterone replacement therapy following spinal cord injury and aging: A mini review.

Context Hypogonadism is a male clinical condition in which the body does not produce enough testosterone. Testosterone plays a key role in maintaining body composition, bone mineral density, sexual function, mood, erythropoiesis, cognition and quality of life. Hypogonadism can occur due to several underlying pathologies during aging and in men with physical disabilities, such as spinal cord injury (SCI). This condition is often under diagnosed and as a result, symptoms undertreated. Methods In this mini-review, we propose that testosterone replacement therapy (TRT) may be a viable strategy to improve lean body mass (LBM) and fat mass (FM) in men with SCI. Evidence Synthesis Supplementing the limited data from SCI cohorts with consistent findings from studies in non-disabled aging men, we present evidence that, relative to placebo, transdermal TRT can increase LBM and reduce FM over 3-36 months. The impact of TRT on bone mineral density and metabolism is also discussed, with particular relevance for persons with SCI. Moreover, the risks of TRT remain controversial and pertinent safety considerations related to transdermal administration are outlined. Conclusion Further research is necessary to help develop clinical guidelines for the specific dose and duration of TRT in persons with SCI. Therefore, we call for more high-quality randomized controlled trials to examine the efficacy and safety of TRT in this population, which experiences an increased risk of cardiometabolic diseases as a result of deleterious body composition changes after injury.

Disruption in bone marrow fat may attenuate testosterone action on muscle size after spinal cord injury: a case report.

BACKGROUND: Mesenchymal stem cells can be differentiated into muscle satellite cells. Testosterone replacement therapy (TRT) promotes the differentiation of satellite cells into muscle cells. CASE REPORT: A 31-year-old male with a T4 complete chronic spinal cord injury (SCI) had fixation for a mid-shaft fracture of the left femur. The participant received transdermal testosterone patches (4 mg/day) daily for 16 weeks. Skeletal muscle and yellow bone marrow adiposity cross-sectional areas (CSAs) of both thighs were measured using magnetic resonance imaging. CLINICAL REHABILITATION IMPACT: The yellow bone marrow CSA was 67-69% lower in the left femur compared to the right femur. Following intervention, a discrepancy was noted between the whole skeletal muscle CSAs of the right (+13%) and left (+6%) thighs. The right knee extensor CSA increased by 7% with no changes in the left CSA. Disruption in bone marrow fat may attenuate the systemic effects of TRT on muscle size.

Military Deployment May Increase the Risk for Traumatic Brain Injury Following Deployment.

OBJECTIVE: To compare rates of traumatic brain injury (TBI) diagnosis before and after overseas military deployment. DESIGN: We conducted a retrospective examination of a cohort of 119 353 active duty US military service members (Army, Navy, Air Force, and Marines) whose first lifetime overseas deployment began at any time between January 1, 2011, and December 31, 2011, and lasted at least for 30 days. For this cohort, TBI diagnoses were examined during the 76 weeks prior to deployment, during deployment, and 76 weeks following the end of deployment. MAIN MEASURES: 4-week rates of TBI diagnosis. RESULTS: The risk of being diagnosed with TBI within 4 weeks after returning from deployment was 8.4 times higher than the average risk before deployment. The risk gradually decreased thereafter up to 40 weeks postdeployment. However, during the 41 to 76 weeks following deployment, risk stabilized but remained on average 1.7 times higher than before deployment. CONCLUSION: An increased rate of TBI diagnosis following deployment was identified, which may be partly due to delayed diagnosis of TBIs that occurred while service members were deployed. Also, the increased rate may partly be due to riskier behaviors of service members following deployment that results in an increased occurrence of TBIs.

Opioid endocrinopathy.

OBJECTIVE: The use of prescription opioids has increased dramatically over the past 20 years. Opioids appear to affect multiple endocrine pathways leading to abnormal levels of different hormones such as testosterone, cortisol, and prolactin (PRL). In this article, we review the current data regarding opioid effects on the hypothalamus, pituitary, and bone metabolism. METHODS: We conducted a PubMed search for articles regarding opioids and each of the following subjects: testosterone, estrogen, cortisol, thyroid, growth hormone (GH), and bone. Most articles were primary source studies conducted between 1980 and 2014. Articles were included if studies were conducted within the time period, published in English, and available as full-length articles. Case reports were reviewed, but controlled studies were given more weight. RESULTS: Opioids appear to affect each of the pituitary hormone pathways in addition to altering bone metabolism. The most commonly reported and substantial effect was hypogonadism in both sexes; however, suppression of the adrenal axis may be more common than initially thought. Although some studies report a change in thyroid and GH levels, overall effects have not been thoroughly studied. There is some evidence for increased fracture risk, possibly mediated by hypogonadism and fall risk. CONCLUSION: More research is needed to determine which opioids are more likely to cause endocrine dysfunction and which patients need to be screened and treated. Also unknown is the length of time to the development of hormonal changes after starting opioid therapy and if cessation of opioid therapy can normalize hormone levels.

Clinical utility of denosumab for treatment of bone loss in men and women.

While most older patients with osteoporosis are treated with antiresorptive bisphosphonates such as alendronate, risedronate, ibandronate, and zoledronic acid, such drugs have side effects, remain in bone for extended periods, and lead to poor adherence to chronic treatment. Denosumab is a humanized monoclonal antibody and antiresorptive agent that works by decreasing the activity of the receptor activator of nuclear factor kappa B ligand. In major trials in postmenopausal women, denosumab increased bone mineral density by dual energy x-ray absorptiometry in the spine, hip, and distal third of the radius and decreased vertebral, nonvertebral, and hip fractures. Denosumab is administered by subcutaneous injection every six months, suggesting that adherence may be improved with such therapy. In addition, pharmacokinetic studies measuring bone turnover markers imply that the antiresorptive effect diminishes more quickly over time. Whether these properties will lead to fewer long-term side effects needs to be proven. Denosumab has also been studied in men with prostate cancer treated with androgen deprivation therapy. These men, at high risk for fracture, also have increases in spine, hip, and forearm dual energy x-ray absorptiometry, as well as fewer morphologic vertebral fractures on x-ray. Denosumab is approved for postmenopausal women with osteoporosis in the US and Europe and for men on androgen deprivation therapy in Europe.