TBI, PTSD, and Low Testosterone: How TRT improves cognitive health

Close to 80% of men with TBI or PTSD suffer from low testosterone. Medical researchers have proven that testosterone replacement therapy has the ability to improve brain function, concentration, and general wellbeing reducing the life-altering strain these brain injuries have on men.

With the pituitary gland sitting near the base of the brain, it leaves it vulnerable to serious impact if the brain is hit or shaken violently requiring it to absorb tons of pressure. As we talk about throughout our articles, the pituitary gland is the “master gland” and key engine for the hypothalamus-pituitary axis to dance a sensitive dance of triggers allowing the body to produce enough testosterone, growth hormone, and estrogen to function normally.

When TBI and PTSD cause damage to the hypothalamus-pituitary axis, communication between the brain and testicles derail the delicate sequence leading to the standard low testosterone symptoms. Reference

How does the brain use testosterone?

Testosterone plays a key role in the brain from organizational to bodily activation effects. Testosterone helps keep the psychophysiology (mental process) of the brain running smoothly. There is a strong dependency on testosterone in cognitive, emotional, and biobehavioral functions as well. Researchers have confirmed many times over that as men age, testosterone naturally decreases hindering the brain’s normal functions.

Looking back at our main symptoms for low T, brain fog and moodiness are common among men over 35 years of age.

TRT helps bring testosterone levels back to optimal ranges promoting healthy brain activity from neurophysiology, sexuality, psychology, to aging leading to an improved quality of life.

A deeper look at how testosterone helps the brain function centers around the psycho-neuro-endocrinological relationship between the body, mind, and hormones. There are three main behavior regulators inside the brain.

• The amygdala is an area with tons of androgen (testosterone) receptors playing a critical role in brain activity. Testosterone “feeds” the bed nucleus of the stria terminalis (BNST), which is the connector between the amygdala and hippocampus and moderates essential emotional processing regions like the prefrontal cortex.
• The prefrontal cortex is the part of the brain that moderates social behavior, personality expression, and decision making. Too much BNST leads to the production of cortisol causing anxiety.
• Finally, the hippocampus helps formulate new memories, learning, and emotions.

Testosterone regulates stress responses in all three of these brain regions. Without proper testosterone levels, stress response inside the brain throws off the hypothalamus-pituitary axis leading to mental fogginess and moodiness.

Several signs of impaired cognitive function in men with low testosterone stand out in these areas.

• Episodic memory: The recollection of past events that happened in a particular place and time.
• Working memory: The ability to remember and use information in real-time while in the middle of an activity.
• Processing speed: The time it takes to do a mental task. Reacting to information received visually, audibly, and in movement.
• Visual-spatial processing: How the brain comprehends scenery and images, and depth perception.
• Executive function: The self-regulating function of the brain such as working memory, shift thinking between situations, and self-control.

All of these areas are regulated by the androgen (testosterone) receptor regions in the amygdala, BNST, and hippocampus. Reference, Reference

Testosterone and Anxiety

Chronic stress causes alterations in brain function leading to anxiety and depressive disorders affecting the hippocampus, amygdala, and prefrontal cortex. When men suffer from low testosterone, the brain basically minds the gap with cortisol leading to elevated heart rate and high blood pressure.

Testosterone is a protective agent the brain uses for hippocampus cell growth and recovery specifically during the initiation of recovery.

The amygdala plays an important role in anxiety and fear responses. With the number of testosterone receptors in the amygdala, testosterone influences the degree of activation in relation to fear reduction. When testosterone levels are low, the highly sensitive receptors have nothing to “feed” on, so the amygdala has nothing to fend off fearful thoughts.

Testosterone naturally converts to estradiol in men. This process is called aromatization. During TRT, studies have proven that the aromatization of testosterone to estradiol actually has an anxiety-reducing effect on the amygdala.

The bed nucleus of the stria terminalis BNST controls of emotions when responding to anxiety and stress. BNST is extremely sensitive to testosterone so if levels are low, emotional response takes a toll on cortisol and adrenaline elevation (fight or flight).

Testosterone helps the brain organize neuronal circuits. Testosterone also helps metabolize new cells during the activation of these neuronal circuits.

In men with low testosterone, research shows that testosterone replacement therapy helps decrease cell oxidation, damage, and structural alterations in the hippocampus. Testosterone replacement has a protective effect on the development of anxiety in long-term social isolation.

Testosterone and Stress

During stressful situations, hormones stimulate the sympathetic adrenal medullary (SAM) division of the nervous system, which is responsible for producing epinephrine and norepinephrine aka adrenaline. Once the SAM begins to release adrenaline, men will see an increased heart rate, elevation in blood pressure, and narrowing of the blood vessels.

The series of events that causes the body to produce stress hormones is pretty interesting.

Stress activates the endocrine axis via the hypothalamic paraventricular nucleus (PVN), which tells the body to release peptides corticotrophin-releasing hormone (CRH).

Corticotrophin-releasing hormone (CRH) stimulates adrenocorticotrophic hormone (ACTH) from the pituitary gland, which produces cortisol into the bloodstream.

Constant stress to the endocrine axis results in excess cortisol and glucocorticoids damaging the body’s natural ability to fend off the negative effects.

The chronic negative impacts lead to mental illnesses such as PTSD, anxiety disorder, and major depressive disorder. All of this can occur when testosterone levels are low. As men age, TRT helps bring testosterone back to normal levels, which has a dampening response to stress. Reference, Reference

Testosterone and Depression

Testosterone plays a critical role in how to brain uses neurotransmitters to fight off mental illness. In men with depression, testosterone can increase dopamine release in the mesolimbic system (the reward pathway), which may protect against the inability to feel pleasure (anhedonia) caused by depression.

Testosterone and Spatial abilities

Spatial ability is the brain’s ability to understand, reason, and remember the spatial relations among objects or space. Spatial awareness declines with age and it is well documented that testosterone has a direct impact on these abilities. Reference

Traumatic brain injury and Pituitary Gland

According to researchers, 30 to 50% of TBI victims have also sustained a pituitary injury due to the violent movement during the event. From hard-hitting head injuries to professional athletes and to returning Iraq and Afghanistan war veterans (veterans in general) fill the majority of people who suffer from traumatic brain injuries (TBI).

The most common pituitary hormones that are negatively impacted by TBI are growth hormone (GH) and follicle-stimulating hormone + luteinizing hormone (FSH/LH).

• Growth hormone (GH), helps adults maintain healthy muscle tissue, body composition, and well-being. Normal levels of growth hormone (GH) has numerous anti-aging effects and also helps adults maintain bone density.
• Follicle-Stimulating Hormone (FSH) controls the production of sperm. FSH levels typically do not change much in men.
• Luteinizing hormone (LH) helps men produce testosterone. Low levels of LH indicate possible issues with your pituitary gland.

Other hormones produced and stored by the pituitary gland include:

• Prolactin increases luteinizing hormone (LH) receptors in Leydig cells, which produces testosterone and leads to spermatogenesis.
• Adrenocorticotropin (ACTH) is a stress hormone that produces cortisol helping to maintain blood pressure and blood sugar levels when the body is under stressful situations. Chronic cortisol can be damaging to the body.
• Thyroid-stimulating hormone (TSH) causes the thyroid gland to produce hormones that regulate metabolism, energy balance, growth, and nervous activity. TSH affects the metabolism of testosterone and all forms of T monitoring sex hormone-binding globulin (SHBG) controlling the levels of free and bound testosterone levels – the sum of these levels = total testosterone levels.
• Antidiuretic hormone (ADH) or arginine vasopressin (AVP) helps the kidneys balance the amount of water in your body.

The pituitary gland does many things for the body that it has POTUS Secret Service-level protection around it. Our anatomy tucks it behind the skull wall well-protected against direct trauma.

The master gland sits inside of saddle-like depression in the skull surrounded by bones called the sella turcica, which in Latin translates to Turkish Saddle. A narrow stem connects the pituitary gland with the brain. Reference

There are portions of the pituitary gland that are more vulnerable to injury than others. Gland cells located in the wings of the pituitary the most exposed because they connect to a single blood source making the wings susceptible to damage during a head injury.

How does TBI affect the endocrine axis?

As you might expect, the hypothalamus-pituitary axis plays a critical role in the response to injury recovery and stress reduction.

In the brain, the pituitary gland affects the neuroactive hormones during the neuronal repair.

Without proper repair, impaired neuroendocrine activity leads to a decline in cognitive, emotional, behavioral, and physical function. Keeping these systems in tip-top shape is essential for optimal neurological and neurobehavioral recovery after traumatic brain and post-traumatic injuries.

During a powerful impact against the skull, the acceleration and sudden deceleration forces strain and whiplash between these sensitive structures. Extreme forces can affect deep and center hippocampus structures like the temporal lobes as discussed above, the diencephalon, which manages sensory and motor signals, and the brain stem, which regulates heart rate, breathing, sleeping, and eating.

TBI-associated low testosterone decreases LH pulse strength, but interestingly not pulse frequency coming from the pituitary gland.

As for IGF-1 and growth hormone (GH), a direct injury to the hypothalamic gonadotropin-releasing hormone (GnRH) neurons, which decreases the LH pulse frequency vs. LH strength.

Post TBI, inflammation begins to be up causing even more damage lower down in the pants where the cytokines (signaling peptide cells) begin to suppress the Leydig cell function literally cutting off production of testosterone in the testicles.

Many pituitary injuries go undetected due to a delay in recognizable symptoms. Most cognitive symptoms of low testosterone are also common TBI symptoms. The pituitary gland control so many processes within the body, possible symptoms include:

• Fatigue, tiredness
• Difficulty concentrating
• Moodiness
• Lack of motivation
• Feelings of isolation
• Infertility
• Weight loss
• Abdominal fat mass accumulation
• Weak bones
• Decreased muscle mass
• VO2Max or aerobic issues – Always out of breath
• High blood pressure
• Heart disease
• Onsite of diabetes

Aside from decreased testosterone levels in TBI or PTSD sufferers, hormone imbalance is actually just as common where there is abnormal activation and deactivation in the hypothalamic-pituitary axis.

Imbalance can launch corticotropin-releasing hormone neurons activates ACTH in the pituitary, which releases the stress hormone cortisol, the salt balancing hormone mineralocorticoids, which can lead to water retention and dehydroepiandrostenedione (DHEA), which stimulates both testosterone and estrogen production.

ACTH is one of the more common deficiencies caused by TBI and PTSD.

A normal pituitary gland will allow cortisol production to increase in times of stress or illness to maintain blood pressure and fight off infection then subside back to stable levels, but when there the ACTH releasing mechanism is broken, cortisol imbalance begins to become a chronic release or simply nonexistent. Reference

Stress disorders and testosterone

According to the National Institute of Mental Health (NIMH), close to 31% of adults in the US experience symptoms of an anxiety disorder at some point in their lives. 8% of Americans suffer from PTSD.

TBI, PTSD, and Veterans

According to the American Speech-Language-Hearing Association and the Department of Defense, Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are frequently comorbid in veterans of the Iraq and Afghanistan wars.

The Department of Defense (DOD) defines the following levels of severity (Defense Health Agency, 2019):

• Concussion or Mild TBI: “loss of consciousness for up to 30 minutes; or confused or disoriented state lasting less than 24 hours; or memory loss lasting less than 24 hours. Excludes penetrating TBI. Results of computed tomography (CT) scan, if obtained, are normal.”
• Moderate TBI: “loss of consciousness for more than 30 minutes, but less than 24 hours; or confused or disoriented state lasting more than 24 hours; or memory loss lasting more than 24 hours but less than 7 days; or meets criteria for concussion/mild TBI but with an abnormal CT. Excludes penetrating TBI. A structural brain imaging study may be normal or abnormal.”
• Severe TBI: “loss of consciousness for more than 24 hours; or confused or disoriented state lasting more than 24 hours; or memory loss lasting more than 7 days. Excludes penetrating TBI. A structural brain imaging study may be normal but usually is abnormal.”
• Penetrating TBI: “open head injury; scalp, skull, and dura mater (outer layer of meninges) are penetrated. Caused by high-velocity projectiles, objects of lower velocity such as knives, or bone fragments from a skull fracture that is driven into the brain.”

Noticeable deficits go from high-level cognitive functions to comatose states.

Survivors may have:

• Loss or limited function of arms or legs
• Slurred speech or language
• Loss of thought and memory
• Emotional problems, aggression or depression

With the clear overlap between PTSD and low testosterone like anxiety, depression, sexual issues, demotivation, and poor stress control the compounding low testosterone issues may contribute to PTSD in patients with a history of TBI.

In a study out of the University of Washington, researchers measured pituitary function in veterans with and without blast-related TBI. Results found that 11 of 26 (42%) with blast-related injuries had hormone imbalances while the control group did not show hormone imbalance. Reference, Reference

In a study out of Yale,

“A 29-year-old male Marine veteran with PTSD and a history of two blast concussions, with brief loss of consciousness, presented with insomnia, emotional detachment, intolerance of crowds, hypervigilance, self-isolation, traumatic memories, hyperacusis, irritability, and explosiveness. These symptoms had persisted despite years of cognitive therapy and psychopharmacologic trials, including an ongoing sertraline and prazosin combination.”

“We tested thyroid, adrenal, and gonadal hormones; IGF-1; and prolactin and found hypotestosteronemia, with an early- morning total testosterone concentration of 240 ng/dL, followed 1 month later by a level of 210 ng/dL (250–800 ng/dL reference range at the Cincinnati Veterans Affairs Medical Center). The circulating luteinizing hormone measure was 0.8 mIU/mL (reference range 1.3–8.6 mIU/mL), consistent with central hypogonadism. This patient also had erectile dysfunction…

The patient, who weighed more than 200 lbs, was started on testosterone gel, 1.62%, at a dosage of 60.75 mg/day. Within weeks of treatment initiation, he reported improved sleep, energy levels, sexual function, concentration, strength, and endurance. Importantly, his irritability and explosiveness were ameliorated and replaced with a sense of increased “calm” and tolerance for others. He even began going to the grocery store during peak hours, which he had previously avoided doing until after 1:00 a.m. These improvements have persisted for more than 1 year with continued testosterone supplementation, which maintains his circulating total testosterone concentrations near the middle of the reference range.” Reference, Reference

Cortisol and Testosterone

Researchers out of The University of Texas look beyond existing research that the association between abnormal cortisol levels and PTSD to see how cortisol and testosterone affect PTSD. The deeper into the complex dance of the pituitary gland and why low testosterone and elevated cortisol causes PTSD.

“Recent evidence points to testosterone’s suppression of cortisol activity, and vice versa. It is becoming clear to many researchers that you can’t understand the effects of one without simultaneously monitoring the activity of the other,” said the author, Robert Josephs. “Prior attempts to link PTSD to cortisol may have failed because the powerful effect that testosterone has on the hormonal regulation of stress was not taken into account.” Reference, Reference, Reference

As we discuss throughout this article, cortisol is the fight or flight hormone. A catabolic hormone secreted from the pituitary gland in response to physical and mental stress.

The study examples that exercising at 60% effort elevates a person’s VO2max (maximal oxygen uptake) to a point where the body is under stress naturally releasing cortisol. Post work out and under normal recovery, testosterone, growth hormone, estrogen, and other hormones flood in to flush out the cortisol repairing the body.

Another cool bodily function is the interaction between cortisol and its effects on metabolism.

Once cortisol is released the goal is to help the body maintain blood glucose levels during physical exercise promoting an increase in amino acid movement in the muscles – muscles are crying for help, cortisol is trying to help.

Cortisol also works with the liver to help produce enzymes to convert amino acids and glucose into energy.

Testosterone is essentially the exact opposite of cortisol that helps prime the pipes for heart and liver health to muscle and bone structure. Low testosterone causes many of the physiologic functions to derail leading to many uncomfortable symptoms.

During physical exercise, testosterone moves in after cortisol floods in to build, recover, and repair the body.

Even inactive men need testosterone more so than active people.

Stagnant or sedentary men run the risk of reduced muscle and increased fat around the waist, which increases the risk for diabetes and other long-term issues. Many studies prove that compounding weight gain leads to low testosterone as the liver does not have enough hormonal activation to fire off and convert fat to energy. Testosterone levels peak near the end of an exercise to begin the healing process, but when men suffer from low testosterone, there is nothing there to counteract the cortisol that lingers in muscles thus compounding the breakdown of muscles opening the door for damage and injury. Reference

Researchers from Harvard doubled down and looked at how cortisol affects low testosterone and leadership abilities.

Ongoing stress and anxiety can lead to the continuous release of cortisol hindering testosterone production so much so that cortisol can kick testosterone while it’s down leading to hypogonadism aka low testosterone. Excess cortisol leads to insomnia, forgetfulness, a weak immune system, mood swings, depression, high blood pressure, and heart disease.

The Fight or flight stress hormone is a powerful tool driving instinct but can tarnish decision-making abilities.

Many studies reveal that as cortisol increases, leadership abilities decrease thus leading to low testosterone.

• Low Testosterone + Low Cortisol: Low strength and confidence, but very calm and relaxed – a “Go with the flow” type. However, dealing with stressful situations may be difficult.
• High Testosterone + Low Cortisol: Confident, strong, calm under pressure, and manages stress effectively.
• Low Testosterone + High Cortisol: lack of confidence, shows as uneasy, and appears nervous. Sweaty palms.
• High Testosterone + High Cortisol: Overly confidence leading to irrational decision making and unwarranted outbursts.

How TBI and PTSD affect sex drive

More than 50% of people who experience a traumatic brain injury suffer from low sex drive. Eagers subside by way of physical or mental disabilities such as depression or anxiety. This is driven by the fact that the pituitary gland is not allowing the necessary hormones to release properly. Reference

• 40 to 60% of men experience temporary or permanent erectile dysfunction (ED) post TBI.
• Roughly 40% of people have difficulty reaching orgasm.

Men’s sex drive and sexual performance begin inside the cerebral cortex and limbic system. When men suffer from low testosterone, there is a clear disconnect between the pituitary gland, testicles, and these two areas. The endocrine axis is out of whack.

As many men know, these areas of the brain are so powerful that men can orgasm from thinking about or dreaming about sex aka wet dreams. The cerebral cortex is responsible for planning and thinking making up the outer layer of the brain. When aroused, signals starting in the cerebral cortex trigger various parts of the brain and nerves that speed up heart and redirects blood flow to the party in your pants causing an erectile.

The limbic system includes the hippocampus, hypothalamus, and amygdala driving emotion, motivation, and sex drive. During sexual thought, the amygdala begins to fire off signals to rallying the troops to let them know that the time is right.

As we know from the brain section, the amygdala has tons of testosterone receptors to signal, trigger, and fire off sex drive – if there is not enough testosterone in circulation these receptors have nothing to tell the cerebral cortex and limbic system that it’s sexy time. Reference, Reference

How does cortisol impact PTSD?

It is well known that cortisol impacts men with PTSD and excess cortisol is a major cause of the disorder. Reference

There are several signs of PTSD that center around stressful and traumatic events. Common symptoms are re-experiencing traumatic events, which causes cortisol to spike and testosterone levels to reduce to medically low levels.

These re-experiencing events can be involuntary and intrusive flashbacks to distressing memories, bad dreams, and intrusive thoughts.

Staying away from certain places or objects that trigger thoughts of a past traumatic event also accelerates cortisol production and cuts off testosterone. PTSD also shows its self through cognitive distress where men might have trouble recalling events or the feeling of worthlessness leading to depression. All of these cognitive issues have a negative compounding effect on testosterone production leading to hypogonadism (low testosterone).

As part of the cognitive distress, arousal symptoms like startling stimuli that resemble the traumatic event causes the fight or flying response, which can be extremely taxing on the body. Some men suffer from night terrors, which impairs sleep and lack of sleep hinders the body’s natural recovery, which occurs during deep sleep. Growth hormone (GH) and testosterone levels release to repair and refresh the body back to normal.

Reference, Reference, Reference, Reference, Reference, Reference, Reference, Reference, Reference

Medically peer reviewed by Jessica Zimmer, PA-C. Written by Our Editorial Team.

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