Hormone Abnormalities Following Traumatic Brain Injury: Deep Dive

My last post was a light dive into the connection between neurosteroids and traumatic brain injury (TBI). I have great respect for Dr. Gordon who developed the neuroendocrinology TBI protocols and I have great respect for my doctor, Dr. Donaldson, for helping me get my life back with these protocols.

The hypothalamic-pituitary axis is often affected by brain injury leading to hypopituitarism. While every brain injury is different and unique, the root of each is an inflammatory state in the brain. I highlighted growth hormone and its importance in my last post, however, I want to give all of the hormones the attention they deserve.

Hormones have been found to affect neuroplasticity, or the brain’s ability to regenerate and grow new connections. If the hormones are depleted, what does this mean for the brain’s ability to heal those damaged areas and neurons? What would the number of post concussion syndrome (PCS) patients look like if there were a screening process in place for these hormonal deficiencies? Would it still be as high as up to 60% of patients going on to experience PCS?

Did you know that up to over half of all individuals who sustain TBI will become depressed within the first year after the injury with some research showing up to 77% and greater than 60% within seven years?^1-3 Various research articles suggest a two to three-fold increased risk of suicide following brain injury versus those who had not suffered brain injury.

Rather than identifying the driving force of the depression, most patients are placed on one antidepressant or a combination. Or like myself, you start to go down the entire list of them because the side effects are intolerable. One might say, “Well, the cause of the depression was the brain injury.” But that doesn’t actually identify the underlying cause. This is if the association to the brain injury was made. What exactly occurred in the brain from the trauma that led to the depression? And why might depression not develop or present in these patients until years later? Now we are looking back at this cascade in the brain and long-term inflammation, damaging neuro-connectivity and leading to the hormonal disruption described here.

Here is an interesting Table from Dr. Gordon’s TBI book showing just how many articles have been published on the association between depression and hormone deficiencies from 2000-2012 alone:

I was actually quite surprised seeing the numbers. This is way more than expected and surprising as hormonal deficiencies are most often not explored or investigated as a cause of depression prior to starting antidepressants despite literature being readily available for many years.

Hormones are powerful and quite miraculous messengers. They work as a team throughout the body with a system of checks and balances. The organs secrete the hormones, these messengers travel to their target destination where they find a specific receptor just for them. When the specific messenger has reached the receptor and binds, cell behavior changes which allows the specific function of the organ or process to change and act.

After taking my idea of hormonal involvement to several of my doctors and didn’t get very far, I sought out care from a functional medicine doctor. The only hormone testing done was for cortisol, which was found to be low throughout the day, though this was predicted and was not surprising. I still had this feeling like there was more out of balance than just that but this was the expert who was trained to look at the big picture, and at that point I was sort of clueless about hormone treatment so I went with it.

If hormonal deficiencies are identified, standard hormone therapy may only replenish one or two deficiencies, but others are often overlooked. This leads to further imbalance in the system. The hormones of the body all working together is like a magical symphony. If just one hormone is insufficient or lacking, others will follow and not function effectively. They all play such an important role and getting them to function collectively and optimally is a careful process that requires fine tuning.

I think of tuning my violin. The big pegs at the one end of the violin just beyond the neck are the initial doses of hormones while the small fine tuners at the opposite side of the violin beyond the bridge are what is needed to very meticulously and finely adjust the dosage. If you turn the big peg of one string too much, another string may reactively go out of tune. The result will be a lack of balance and lack of harmony, just the same as hormones. The small fine tuners of the violin often save the day; moving it just a millimeter will allow the perfect pitch. When playing for long periods of time, you have to continuously reassess and fine tune the strings. Through time, each hormone is reassessed and fine-tuned, similar to tuning the violin. This is an ongoing, meticulous process, that requires a delicate balance.

Let’s give these powerful messengers the credit they deserve! I now realize fully just how important each individual hormone is to function optimally. Even small changes in hormone levels can lead to big changes in the body and wreak havoc. Case in point – my life over the past 2.5 plus years.

It is important to note that there are broad ranges given for all of the hormones and if your lab result falls into the “normal” range you may not be treated even though that may not be optimal. A low-normal result, or sub-optimal result, can cause a multitude of symptoms as well.

What happens if certain hormones go haywire? What symptoms might one experience with specific deficiencies? In this post, I will dive deep into the hormonal abnormalities and symptoms that can arise with each. The symptoms overlap for many. If you take only one thing away from this, let that be that hormones are so powerful and if we channeled the time spent on picking out the next pharmaceutical drug for a patient on finding the underlying cause of the symptoms, we would be in a much better place.

Command, do you copy?

The command centers of the hormones are located in the brain in the hypothalamus and pituitary gland. Signals are received by the brain which are then sent to the hypothalamus where the signals are translated into the hormone language. This is passed along to the pituitary gland which then causes further signaling, to release a particular hormone. These will either act directly on certain processes or indirectly by signaling other endocrine glands downstream.

The hypothalamus resides between the pituitary gland and the inner brain, connecting the endocrine and nervous systems. It plays such an important role in the release of hormones such as growth hormone-releasing hormone (GHRH) which regulates growth hormone production, thyrotropin-releasing hormone which regulates thyroid hormone release, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which regulate sex cell production, corticotropin-releasing hormone (CRH) regulating adrenocorticotropin release which regulates the stress response through cortisol production. If damage or inflammation occurs in the brain throwing off any of these hormones, these powerful messengers are unable to signal the proper channels.

The pituitary gland is the size of a pea and is small but mighty. Do not underestimate its power or role. We must protect the pea! It resides at the base of the brain and is considered the “master gland” as it plays the central role in the endocrine system. The gland has an anterior and posterior lobe which in combination regulate the reproductive organs, adrenals and thyroid. The messengers come from the hypothalamus and in turn, the pituitary releases growth hormone, stimulates the thyroid gland to produce thyroid hormones by releasing thyrotropin, the adrenal gland to produce cortisol by releasing corticotropin. It also secretes prolactin, allowing new mothers to produce milk but is also involved in many other functions.

The posterior lobe of the pituitary releases antidiuretic hormone (vasopressin) helping to maintain water balance in the body and oxytocin which has been called the “love hormone,” but also serves other functions too. Serving as the master gland and having such a governing role in the body, you can imagine that damage or inflammation can lead to inhibition or activation of these hormones and the regulatory processes, leading to many issues.

Growth Hormone

I’m starting with the boss. I call growth hormone (GH) the boss because it influences every other hormone in the body. Not only that, but GH is found in every tissue in the body. If something happens to the boss who is supposed to communicate with the workers of the body (cells and other hormones down the line) and tell them what to do, the system fails. The communication is dysfunctional, the workers don’t do their jobs effectively or go on strike. It can turn into a mess.

When you think of growth hormone, you may think of its importance in childhood only. This is what allows you to grow and become an adult. The importance carries on into adulthood, in a big way.

Effect: mood, stress, energy, memory, sleep, immune system, sex, circulation, bones, joints, weight, skin and hair.

GH deficiency can lead to: depression, anxiety, fatigue, difficult recovering from physical activity, thinning hair, weight gain, slack muscles, loss of muscle mass, thin or dry skin, wrinkles, saggy cheeks, poor sex drive, difficulty relaxing, poor endurance, dream infrequently, sleep for long periods but do not feel refreshed, sensitivity to sun, slow wound healing or easy bruising, grey hair, thick folds of skin, fat hump on upper back, loss of muscle mass or strength, tense muscles, poor sleep, memory problems, high blood pressure, irritability, worried, poor cardiac artery health, high cholesterol or high LDL and low HDL (good), arthritis, bone loss in the spine, stomach saggy, labs showing low immune function.

DHEA

Dehydroepiandrosterone (DHEA) and when sulfated to its active metabolite, DHEA-S, play a significant role in the brain but also peripheral organs. DHEA-S is able to stimulate glial cells into making myelin, the insulating sheath around neurons. DHEA transforms down the chain to become testosterone and estrogen. More DHEA will be secreted over your lifetime than any other hormone! DHEA helps enhance immunity, memory, decrease joint pain, increases energy levels, and quells excess cortisol levels, among many other functions.

Effect: mood, stress, energy, memory, sleep, immune system, sex, circulation, bones, joints, weight, skin and hair.

DHEA deficiency can lead to: depression, flabby muscles, loss of muscle mass, lack of hair in the pubic area, low libido, lack of sexual odors, dry hair, excessively dry skin, dry eyes, fat belly, noise intolerance, memory problems, high cholesterol, high blood pressure, bone loss in the spine, easily worried or excitable, difficulty recovering from physical activity, labs showing low immune function, low antibodies.

Testosterone

Contrary to popular belief, testosterone is one of the most important hormones for men and women both! Naturally, decline in women starts in the 20s and for men in the 30s. Not just important for libido of both sexes, it also reduces the risk of heart disease by protecting the arteries, and protects the kidneys and pancreas. It is important for the prevention of osteoporosis, joints and muscles, hair growth, energy and stabilizing mood.

Effect: mood, stress, energy, memory, sleep, sex, circulation, bones, joints, weight, skin and hair.

Testosterone deficiency can lead to: depression, loss of muscle tone, belly becomes flabby, damaged arteries or atherosclerosis, weak heart beat, tired constantly, low libido, face with more wrinkles, difficulty recovering from physical activity, excessively dry skin, lack of sexual odors, pale skin, thin skin, wrinkles at the corners of the eyes, dream infrequently, fat hump on upper back, poor sleep, slow wound healing, arthritis, memory problems, easily worried or excitable, sensitivity to the sun, hair turning grey, high cholesterol, high blood pressure, bone loss in the spine. Specific to men – feeling less confident, dream infrequently, hot flashes, tired with physical activity, breasts become fatty, decreased sexual performance, hair loss to top of head, lower abdomen, chest or legs.

Progesterone

When many think of progesterone, the first and maybe only thought is its importance in the menstrual cycle but its role goes much beyond that. Progesterone has been found to be highly protective of the brain, quelling inflammation, swelling and protecting the blood-brain barrier (regulates what passes into the brain). Progesterone has a calming effect as it binds to GABA receptors in the brain, which in turn can help with anxiety, sleep troubles or restlessness.

The sparked interest in progesterone and its role in TBI recovery stems from a study of female rats in which they experienced induced TBI and given progesterone which led to better recovery and improved outcomes. Subsequent studies showed similar results in animals. Further studies in humans showed promise but more studies need to be conducted to validate these results.

Effect: mood, stress, energy, memory, sleep, immune system, sex, circulation, bones, joints, weight, and hair.

Progesterone deficiency can lead to: depression, memory problems, swollen and tender breasts before period, irritability, heavy periods, painful periods, bloating of lower abdomen, nervousness, agitation, anxiety, tense muscles, sleep is restless or light, hair loss on top of head in women, dream infrequently, easily worried or excitable, difficulty relaxing.

Estrogen

Translated from ancient Greek, this is the “generator of desire.” Estrogen serves hundreds of functions in the female body. Well known for its function in the reproductive system, it also plays many non-reproductive roles. Let it be known that estrogen is important and needed in men too! Estrogen plays important roles in the brain by blocking a brain enzyme called monoamine oxidase, which allows important mood-simulating neurotransmitters to act longer and stronger. It also creates catecholestrogens which are neurotransmitters that act as mental stimulants. These two functions can aid in the reversal of depression or prevent it in the first place. It improves blood flow and is a powerful antioxidant.

Some research has looked into where a woman was in her menstrual cycle when she sustained a brain injury and how that may play a role in recovery. Estrogen seems to offer a degree of protection to the brain just as progesterone.

Effect: mood, stress, energy, memory, sleep, immune system, sex, circulation, bones, joints, weight, skin and hair.

Estrogen deficiency can lead to: depression, arthritis, irregular menstrual cycle in women, damaged arteries, hot flashes, excess facial hair, fatigue, loss of muscle mass, lack of sexual odors in women, lack of vaginal lubrication, hair loss on top of head, excessively dry skin, pale skin, thin skin, wrinkles at the corners of the eyes, high cholesterol, high blood pressure, difficulty recovering from physical activity, memory problems, dream infrequently, poor sleep, bone loss in the spine. In men specifically – low libido, infertility.

Cortisol

I always associated cortisol with stress but it is so important for reducing stress and has been referred to as the “anti-stress hormone.” The rise of cortisol when under stress actually allows your body to manage and expel the stress. Cortisol not only helps us to quickly respond to stressful situations but also reduces inflammation, influences appetite, increases energy, aids in digestion and even enhances function of the immune system.

Effect: mood, stress, energy, memory, sex, immune system, circulation, bones, joints, weight, skin and hair.

Cortisol deficiency can lead to: weight loss, face looks thinner, allergies, feeling stressed out, digestive issues, arthritis, weak or fast heartbeat, trouble concentrating, being easily confused, salt or sugar cravings, skin issues (eczema, psoriasis, rashes), low blood pressure, light headed in stressful situations, circular patches of hair loss, swollen moon face, feeling wiped out from the least amount of stress, fat hump on upper back, sleep for long periods but do not feel refreshed.

Pregnenolone

Often referred to as the “mother of all hormones,” as it is the first steroid generated from cholesterol and goes on to be the start of two key pathways, ending up as aldosterone/cortisol and testosterone/estrogen. Insufficient levels of pregnenolone can cause a spiral effect down the line. This steroid is found in the brain, and highly concentrated specifically in the hippocampus. It is so important for memory. A fun fact about this one is that with replenishment, it can intensify or enhance the way you see colors.

Effect: memory, joints.

Pregnenolone deficiency can lead to: low blood pressure, craving salty food, memory loss, difficulty handling stress, joint pain, lack of hair in pubic area or under arms, flabby muscles, excessive light-colored urine during the day, feeling drained, not seeing colors as brightly, difficulty trusting your memory.

Thyroid

The pituitary gland produces thyroid stimulating hormone (TSH) which stimulates the thyroid gland to produce triiodothyronine (T3) and thyroxine (T4). Situated at the anterior base of the neck is the thyroid gland. These hormones serve a pivotal role in growth and development, blood circulation, metabolism, the nervous system. The thyroid hormones stimulate the mitochondria of the cells and protects the brain, heart, kidneys, immune system and digestive organs. The effect on blood circulation aids in removing waste from arteries and cells and also dissolving cholesterol.

Effect: mood, stress, energy, memory, sleep, immune system, circulation, bones, joints, weight, skin and hair.

Thyroid deficiency can lead to: cold hands and feet, puffy face and eyelids in morning, sensitivity to cold, easily put on weight, arthritis, constipation, pale skin, feeling more tired at rest than when moving, dry hair, brittle hair, hair loss, slowed thinking, excessively dry skin, stiff joints in the morning, fat hump on upper back, trouble getting up in the morning, high cholesterol, weak heartbeat, high blood pressure, sleep for long periods but do not feel refreshed, trouble concentrating, memory problems, labs showing low immune function.

ACTH

Adrenocorticotropic hormone (ACTH) oversees the production of the anti-stress hormone, cortisol. The effects are not just limited to that; it also plays a role in hair growth, skin color or tan, and is also an important messenger for neurons in the brain. ACTH is important for keeping you cool by building up stress resiliency and helps with mental focus and attentiveness.

Effect: stress, energy, memory, joints, skin and hair.

ACTH deficiency can lead to: feeling stressed out, low blood pressure, weight loss, memory loss, patches of hair loss, hair turning grey, pale complexion, trouble concentrating.

Insulin

Insulin has the primary role of stabilizing and maintaining blood-sugar levels. Not only that, but it plays a role in strengthening arteries and protecting against heart disease. It enhances the immune system and aids in the digestive system. Insulin provides you with energy, strengthens muscles and stores fat as energy reserves.

Effect: mood, energy, sex, circulation, immune system, sleep, weight, skin.

Insulin deficiency can lead to: loss of muscle mass, lack body fat, skinny buttocks and stomach, excess urination in day and night, sugar cravings, excessive thirst, poor healing, lack energy for tiring work.

Vitamin D

I didn’t want to leave this one out. Surprise! Vitamin D is actually a hormone. Many different types of cells have receptors for it throughout the body. It serves such an important role in the immune system, bone health, mental health, a healthy gut microbiome and cardiovascular health.

In several research studies, vitamin D has been shown to protect the neurons of the brain through its powerful immune-boosting and anti-inflammatory capabilities. Deficiency in vitamin D following TBI is common and has been associated with more severe depressive symptoms and worsened cognitive function. Low vitamin D status has been associated with a higher incidence of inflammatory conditions, cancer and chronic disease.

Sources

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A Light In Pittsburgh

Over the past two and a half years, I have listened to hours and hours of TBI podcasts to learn more and seek out new treatment options. I heard one about neurosteroids and neuroendocrinology around one year following my injury. I already had a suspicion about six months after my injury that I had some sort of hormonal dysregulation going on. After trying over 20 different medications to treat my symptoms I felt even worse from the side effects. I was coming to the conclusion that these drugs were just bandaids, one layered over another, burying the underlying cause even deeper. Could this hormonal dysregulation be the root cause of all of this?

I had brought it up to several doctors who had dismissed it and essentially brushed it off. It seemed like this idea of addressing hormones was shunned. One doctor said to me, “I don’t think hormones really play a role in brain injury recovery.” Because it was dismissed by several doctors, I thought to myself, maybe that was a dumb idea thinking this could be what’s going on with me after all.

I sort of forgot about this until just a couple months ago when I again heard a podcast about addressing hormonal dysfunction and using neurosteroids to treat patients who had suffered TBI. It sounded like it was actually working, like there was so much success with this. The science was there for it. Could this actually work for me? I wasn’t going to bring this to my doctors because I felt like it would be dismissed again. At some point in my recovery, it truly felt like I was fending for myself. Even some of the new treatments I found on my own that actually did provide some positive improvements in my recovery were still brushed aside by some of my doctors.

After I heard of this treatment for a second time in a podcast, I thought, I need to find a doctor who is practicing this type of medicine for TBI. That’s when I found Dr. Valerie Donaldson in Pittsburgh, who completed a four-part certification process taught by Dr. Mark Gordon, pioneer of Neuroendocrinology TBI treatment protocols. I booked an appointment three weeks out and was elated because I didn’t even know if I would be able to get in. I was a little scared to commit to this TBI program because I was thinking, what if it doesn’t work? What if it turns out to be a huge failure or worse, what if it ends up hurting me and setting me back like other treatments? I would never know if I never tried, so I booked the first appointment. February 17, 2021, would be a good day to remember.

My Mom asked me two days before the appointment if we should postpone it because we were getting a huge snowstorm the next few days during the drive. I said, “Absolutely not, we need to make it to Pittsburgh tomorrow.” I couldn’t wait any longer because I was feeling so desperate and somehow it felt like this time would be different. I didn’t want to postpone this appointment even a day. At that point, I felt so desperate I may have even put on several snowsuits and started walking to Pittsburgh in the snowstorm. I was holding onto this thought that maybe this was the last part of my long journey to healing. This could be it. On the other hand, I was bracing myself in case history repeated itself and this was another failure in this journey like many before.

My Mom and I drove to Pittsburgh as planned. It did turn out as a blessing that the snowstorm held off during our driving hours. We drove the day before the appointment because I wouldn’t have been able to tolerate the drive there and back in one day. We stayed overnight which left me with nervous jitters like the night before a big game.

Something that has repeated itself throughout my recovery is that I’ve been treated like a constellation of symptoms rather than a person. Soon after the injury I was seeing 20 different providers for each symptom I was experiencing, none communicating with each other and so instead of a person I became this long list of symptoms. Each appointment was the same – check off the boxes and symptom score, tell me to come back in a month to do it all over again. Nothing new was being offered; I wondered why I was even going anymore. It’s like they gave up on me and weren’t able to offer me any more options to get better. This contributed to my identity crisis. I was struggling to know who I was anymore all while not being treated like a person. It was like kicking me while I was down. This changed in Pittsburgh.

I woke up the next morning – appointment day. I was hoping my insomnia would give me a break, but I only got a couple hours of sleep in. I was nervous, excited, exhausted, foggy. Time seemed to move slowly that morning and I was getting antsy to leave the hotel to go to the appointment.

We made it to the doctor’s office. I stood outside, staring at it, taking a big breath in. “Please let this help me,” I said aloud. It felt almost like I was pleading. I’ve prayed during my recovery but I haven’t felt like my prayers have been answered. I’ve struggled with the reason for all of this, if there is one. We walked into a cute, little office where we were greeted by the secretary with kindness. I was first taken back to have my blood drawn for testing and then joined my Mom back out in the waiting area. I sat there, a little fidgety, until we were called back. I could suddenly hear and feel the presence of my heartbeat. My Mom and I walked back into the doctor’s office.

We were greeted warmly by Dr. Donaldson and took a seat in the two chairs before her at her desk. She was comforting to talk to and I was met with so much empathy, kindness and understanding. Quickly, my nervousness and anxiety melted away. My heart became calm. Her knowledge was extremely humbling. I had said to her that I wanted her to implant all of her knowledge into my brain. When I described something I was experiencing, I didn’t feel degraded but rather understood. I was not being dismissed which had become a norm at many appointments leading up to this.

I walked into my appointment thinking the most impressive thing about the doctor would be her credentials and list of certifications (Internal Medicine, Emergency Medicine, Anti-Aging Medicine, Functional Medicine, Regenerative Medicine) but I left with the most impressive thing being her compassion, empathy, knowledge and ability to make me feel like I was actually being cared for and understood. I felt like I was in the right hands, that would actually do no harm. Not only that but the fact that she was able to bring me hope. And I so desperately needed that to keep going. This was an important reminder that compassion and empathy go a long way and at just the right moment, might be the thing that can bring a person out of a dark and lonely hole. She made me feel like I would be okay. And there are no words for that.

I left the office feeling lighter, like a weight was lifted off my shoulders. I was so overcome with emotion that happy tears streamed down my face. That day made me realize just how dispirited I had become. My visit with Dr. Donaldson provided hope for the first time in two years. It felt like I wouldn’t have to fend for myself anymore.

I felt not only like a person but a person who would get through this. When Dr. Donaldson said she would get me better and I would heal, I believed it because it was genuine. I trusted her. My trust with medical providers through this time period was hindered, leaving me skeptical and wondering if they really cared about my outcome at all. Leaving this appointment with that trust and hope was everything.

This glimmer of hope brought a positive feeling in me that I can’t fully articulate – a refreshing feeling that I had forgotten existed. I don’t want to get my hopes up too high because after seeking so many treatments over the past couple years with many downfalls and setbacks, it’s hard to fully let go of that. I have a really good feeling about this, though. To feel understood and like a whole person rather than a list of symptoms is a rarity these days and I felt that and continue to feel that in appointments with Dr. Donaldson. For now, my spirits are back and I’m going to ride this good wave as I continue in this program and hopefully ride it all the way to full healing.

After going to nearly 300 appointments and seeing my fair share of doctors over the past two and a half years, it had become common for follow up visits with those doctors to be filled with anxiety, stress and even dread. I have not felt this way with Dr. Donaldson. On the contrary, I look forward to my appointments with her and that speaks volumes. I am going to explain what this treatment consists of and this journey further in a future blog post as I continue along.

I am so grateful for Dr. Donaldson. There was a light in Pittsburgh that I so desperately needed. And I have a feeling, it’s just going to get brighter.

DR VALERIE DONALDSON – Regenerative Medicine Center