Effects of Testosterone Replacement Patients with Moderate to Severe Head Injury and Persistent Hypogonadotropic Hypogonadism: An Open-label Randomized Controlled Trial
Chandan H Anandegowda, Srivatsan Thirumalai Vasu, Kanishk Parmar, Vishnu PS, Lakshay Raheja, Haroon Manadath Pillay, Venkidesh Krishnamoorthy and Rahul Srinivasan
Department of Neurosurgery, Medical Trust Hospital, Pallimukku, Kochi, Kerala, India
*Corresponding Author: Chandan H Anandegowda, Department of Neurosurgery, Medical Trust Hospital, Kochi, India.
Received:
July 14, 2021; Published: August 12, 2021
Abstract
Background: Traumatic brain injury (TBI) pertains to the significant potential for brain parenchymal lesions after suffering cranial trauma. Individuals with TBI are at high risk for developing neuroendocrine dysfunction, especially moderate and severe types. This study was conducted to understand relationships between hypogonadism and outcomes at 6 months post-TBI and to study the effect of testosterone supplementation in patients with persistent hypogonadism on the outcome of moderate to severe TBI.
Methods: The study was conducted as an open-label, randomized trial. Males aged 16 - 70 years post-moderate-severe TBI either received injection testosterone 200 mg intramuscularly (IM) every 4 weeks for 3 months in addition to standard care or standard care alone. They were followed up for 6 months. Functional independence measure scoring was used as an outcome measure.
Results: Of 98 patients screened, 62 were initially included. 11 patients expired and 4 did not develop hypogonadism at 3 months and were excluded subsequently from the analysis. Forty-seven patients were randomized to the intervention (n = 24) and control groups (n = 23). There was no significant difference between groups in the improvement on the FIM scores at discharge, 3 and 6 months (p = 0.509, 0.609, and 0.632 respectively). The Treatment group demonstrated the greatest absolute improvement in FIM scores although the results were not significant.
Conclusion: There were no significant differences in functional independence, the intervention group showed greater absolute functional improvement compared to the control group.
Keywords: Testosterone; Traumatic Brain Injury; Persistent Hypogonadotropic Hypogonadism; Functional Outcome
References
- Heegaard WG and Biros MH. “Traumatic Brain Injury”. Emergency Medicine Clinics of North America 3 (2007): 655-678.
- G T and B J. “Assessment of coma and impaired consciousness. A practical scale”. Lancet (London, England) 7872 (1974): 81-84.
- F T., et al. “A systematic review of brain injury epidemiology in Europe”. Acta Neurochirie (Wien)3 (2006): 255-267.
- Hohl A., et al. “Hypogonadism after traumatic brain injury”. Arquivos Brasileiros de Endocrinologia e Metabologia 8 (2009): 908-914.
- Samabasivan M. “Epidemiology of neurotrauma”. Neurology Preventive India 43 (1991): 9-15.
- Ramamurthi B. “Road accidents”. Epidemiology Preventive Neurology India 43 (1991): 9-15.
- Rothman MS., et al. “The neuroendocrine effects of traumatic brain injury”. Journal of Neuropsychiatry and Clinical Neurosciences4 (2007): 363-372.
- Fernandez-Rodriguez E., et al. “Hypopituitarism Following Traumatic Brain Injury: Determining Factors for Diagnosis”. Frontiers in Endocrinology (Lausanne) 2 (2011).
- J W., et al. “Acute gonadotroph and somatotroph hormonal suppression after traumatic brain injury”. Journal of Neurotrauma 6 (2010): 1007-1019.
- AK W., et al. “Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury”. Journal of Neurotrauma 6 (2011): 871-888.
- DJ B., et al. “Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction”. Journal of Head Trauma Rehabilitation 4 (2016): 277-287.
- SA L., et al. “Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury”. The Journal of Clinical Endocrinology and Metabolism6 (2001): 2752-2756.
- A K., et al. “Screening for hypopituitarism in 509 patients with traumatic brain injury or subarachnoid hemorrhage”. Journal of Neurotrauma 1 (2014): 99-107.
- DF K., et al. “Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report”. Journal of Neurosurgery5 (2000): 743-752.
- G A., et al. “Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study”. The Journal of Clinical Endocrinology and Metabolism11 (2005): 6085-6092.
- G A., et al. “Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury”. Clinical Endocrinology (Oxf)3 (2004): 320-326.
- M B., et al. “Occurrence of pituitary dysfunction following traumatic brain injury”. Journal of Neurotrauma6 (2004): 685-696.
- M B., et al. “Anterior pituitary function may predict functional and cognitive outcome in patients with traumatic brain injury undergoing rehabilitation”. Journal of Neurotrauma11 (2007): 1687-1697.
- V P., et al. “Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress”. Journal of Endocrinological Investigation 11 (2004): 1048-1054.
- TP Y., et al. “The role of serum testosterone and TBI in the in-patient rehabilitation setting”. Brain Injury6 (2007): 645-649.
- DL R., et al. “Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: Results from a double-blind, placebo-controlled clinical pilot study”. NeuroRehabilitation3 (2020): 355-368.
- Traumatic Brain Injury Information Page | National Institute of Neurological Disorders and Stroke (2021).
- Bhasin S., et al. “Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline”. The Journal of Clinical Endocrinology and Metabolism5 (2018): 1715-1744.
- Cech DJ and Martin S. “Tink.” Evaluation of Function, Activity, and Participation”. Functional Movement Development Across the Life Span (2012): 88-104.
- HF L., et al. “Early prognosis in traumatic brain injury: from prophecies to predictions”. Lancet Neurology5 (2010): 543-554.
- ME de OT., et al. “Limited predictive power of hospitalization variables for long-term cognitive prognosis in adult patients with severe traumatic brain injury”. Journal of Neuropsychology1 (2014): 125-139.
- Diaz AP., et al. “Psychiatric Disorders and Health-Related Quality of Life after Severe Traumatic Brain Injury: A Prospective Study”. 29.6 (2012): 1029-1037.
- MJ DS., et al. “Patient outcome after traumatic brain injury in high-, middle- and low-income countries: analysis of data on 8927 patients in 46 countries”. International Journal of Epidemiology 2 (2009): 452-458.
- ET M., et al. “Mortality in severe traumatic brain injury: a multivariated analysis of 748 Brazilian patients from Florianópolis City”. Journal of Trauma1 (2009): 85-90.
- Hohl A., et al. “Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients”. Frontiers in Endocrinology (Lausanne) 9 (2018): 29.
- Shekhar C., et al. “An epidemiological study of traumatic brain injury cases in a trauma centre of New Delhi (India)”. Journal of Emergencies, Trauma, and Shock 3 (2015): 131.
- F T., et al. “High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and 12 months after trauma”. The Journal of Clinical Endocrinology and Metabolism6 (2006): 2105-2111.
- I C., et al. “Neuroendocrine responses following graded traumatic brain injury in male adults”. Brain Injury12 (1999): 1005-1015.
- M K., et al. “Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study”. Clinical Endocrinology (Oxf)4 (2007): 598-606.
- A A., et al. “Neuroendocrine dysfunction in the acute phase of traumatic brain injury”. Clinical Endocrinology (Oxf) 5 (2004): 584-591.
- , et al. “Prevalence of hypothalamo pituitary dysfunction in patients of traumatic brain injury”. Indian Journal of Endocrinology and Metabolism 20.6 (2016): 772.
- , et al. “Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?” Indian Journal of Endocrinology and Metabolism 21.1 (2017): 80.
- A H., et al. “Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury”. Brain Injury10 (2014): 1262-1269.
- Olivecrona Z., et al. “Acute neuro-endocrine profile and prediction of outcome after severe brain injury”. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1 (2013): 1-13.
- Wagner AK., et al. “Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI”. 26.10 (2012): 1226-1242.
- RB C., et al. “Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration”. Journal of Neurotrauma 14 (2019): 2246-2259.
- Y K., et al. “Testosterone replacement therapy to improve secondary sexual characteristics and body composition without adverse behavioral problems in adult male patients with Prader-Willi syndrome: an observational study”. American Journal of Medical Genetics9 (2013): 2167-2173.
- N S and F F. “Testosterone treatment of an XXYY male presenting with aggression: a case report”. Canadian Journal of Psychiatry 9 (1988): 846-850.
- DB O., et al. “Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men”. Physiology Behavior 4 (2002): 557-566.
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