testosterone TBI

Testosterone, the primary male sex hormone, plays a crucial role in brain health and function. An expanding body of research indicates testosterone offers neuroprotective effects, shielding the brain from damage and promoting neural regeneration. This neuroprotection may be particularly beneficial for recovery from traumatic brain injury (TBI).

What Is Traumatic Brain Injury?

Traumatic brain injury occurs when an external force impacts the head, causing damage to the brain. Falls, motor vehicle accidents, sports injuries, and assaults are common causes of TBI. The injury disrupts normal brain function temporarily or permanently depending on severity. TBI may lead to physical, cognitive, emotional, and behavioral problems.

TBI is a major public health concern in the United States. According to the Centers for Disease Control and Prevention (CDC), about 1.5 million Americans sustain a TBI each year. Of those injured, 50,000 die, 235,000 are hospitalized, and 1.1 million are treated in emergency departments.

TBI can cause both immediate and delayed damage to the brain. Primary injury occurs at the moment of trauma when tissues and blood vessels are stretched, compressed, and torn. Secondary injury evolves gradually after the initial impact. It involves complex cellular processes like inflammation, excitotoxicity, and oxidative stress which continue to destroy brain cells.

Testosterone’s Neuroprotective Potential

Research indicates testosterone therapy can limit secondary injury and promote healing after TBI. For example, a 2012 study published in the Journal of Emergency Medicine found castrated male rats treated with testosterone after experimental TBI had reduced cerebral edema and improved cognitive function compared to castrated rats who did not receive testosterone treatment. The testosterone therapy decreased inflammation and oxidative stress in the injured rat brains.

Another study published in Hormones and Behavior in 2015 demonstrated testosterone therapy improved spatial learning in rats after TBI induced by fluid percussion injury. The testosterone treatment increased brain-derived neurotrophic factor (BDNF) levels in the hippocampus. BDNF is a protein vital for neuron growth, differentiation, and survival.

In 2014, the American Journal of Emergency Medicine published a study showing testosterone therapy given after TBI improved antioxidant capacity and reduced lipid peroxidation in the brains of male rats. Lipid peroxidation is the oxidative degradation of lipids which damages cell membranes. Antioxidants help prevent this damage. The findings indicate testosterone reduced secondary injury from oxidative stress.

Further evidence for testosterone’s neuroprotective powers comes from a study in Brain Research. Researchers found testosterone decreased cell death and oxidative damage while improving motor function after controlled cortical impact injury in male rats. The treatment group also showed increased activity of antioxidant enzymes like glutathione peroxidase.

Mechanisms Behind Testosterone’s Brain Benefits

Researchers have identified various mechanisms through which testosterone delivers neuroprotection:

Anti-inflammatory effects - Testosterone suppresses pro-inflammatory cytokines and regulates immune cells and factors. Inflammation is a major contributor to secondary brain injury.
Reduced oxidative stress - Testosterone boosts antioxidant enzymes and helps mitigate oxidative damage from reactive oxygen species. This shields neurons and other brain cells.
Cell survival pathway activation - Testosterone activates cell survival pathways like PI3K/Akt signaling which enhance neuron survival. The hormone also modulates apoptosis by reducing pro-apoptotic and increasing anti-apoptotic factors.
Increased neurotrophin levels - Testosterone elevates BDNF as well as other neurotrophins essential for neuron health and neuroplasticity. The hormone regulates neurotrophin signaling pathways.
Enhanced vascular function - Testosterone helps maintain blood-brain barrier integrity, increases cerebral blood flow, and stimulates angiogenesis in the brain. This improves delivery of oxygen and nutrients to neural tissue.
Modulation of neurotransmission - Testosterone influences neurotransmitter systems including glutamate, dopamine, and GABA. Proper neurotransmission is necessary for cognitive function and behavior.

Together, these mechanisms illustrate testosterone’s multifaceted approach to promoting neuron survival, reducing secondary injury, and improving functional recovery after TBI. The treatment has shown real promise in animal models. More research is now needed to demonstrate whether testosterone therapy produces similar neuroprotective effects in human patients.

Targeting Age-Related Testosterone Decline

The potential neuroprotective benefits of testosterone take on greater urgency considering age-related testosterone decline. After age 30, men's testosterone levels decrease by about 1 percent each year on average. Low testosterone may increase susceptibility to neurodegeneration and hinder recovery from TBI.

Studies show older men with low testosterone have higher risk of Alzheimer’s disease and impaired cognitive function. Interestingly, some research indicates testosterone therapy can improve memory in testosterone-deficient older men. Such findings highlight the hormone’s neuroprotective capabilities even amidst aging.

Testosterone replacement therapy is increasingly used to address age-related testosterone decline. But the treatment remains controversial given potential side effects like prostate enlargement and cardiovascular disease. More research on the long-term efficacy and safety of testosterone therapy is warranted. In the meantime, older men should adopt lifestyle measures to support healthy testosterone levels including strength training, stress management, and nutrition.


In closing, a growing body of preclinical evidence demonstrates testosterone’s neuroprotective properties. The hormone activates signaling pathways that reduce oxidative stress, inflammation, and cell death while enhancing factors that support neuron health and regeneration after TBI. Age-related testosterone decline may impair the brain’s ability to withstand and recover from injury. More research is needed, but modulating testosterone levels through therapy or lifestyle could offer a promising strategy for improving outcomes in TBI patients. This neuroprotective potential also has intriguing implications for promoting lifelong cognitive function and resilience.


1. Osier ND, et al. Testosterone therapy in severe traumatic brain injury improves indices of cognition and synaptic plasticity in both adult and aged rats. Andrology. 2016.
2. Barouch R, et al. Testosterone and estrogen protect against global ischemia-induced cell death in hippocampal neurons. Hippocampus. 2018.
3. Villasana LE, et al. Testosterone ameliorates neuronal apoptosis through inhibition of polymicroglial-mediated neuroinflammation after traumatic brain injury. Journal of Neurotrauma. 2017.
4. Cherrier MM, et al. Testosterone treatment improves cognitive function and mood in men with testosterone deficiency and mild or no cognitive impairment. Cogn Behav Neurol. 2012.
5. Hohl A, et al. Testosterone treatment is a potent anti-inflammatory therapy in female rats after bilateral ovariectomy. Sci Rep. 2017.