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
1. Depression in Men and Women One Year Following Traumatic Brain Injury (TBI): A TBI Model Systems Study, 2017, DOI: 10.3389%2Ffpsyg.2017.00634.
2. Major Depression in Patients with Closed Head Injury, 1987, DOI: 10.1037/h0091773.
3. Neuropsychiatric Complications of Traumatic Brain Injury. 2007, DOI: 10/1176/jnp.2007.19.2.106.
4. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population, 2004, DOI: 10.1001/archpsyc.61.1.53.
5. Traumatic Brain Injury, A Clinical Approach to Diagnosis and Treatment, Gordon, 2016.
6. Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury. 2016, DOI: 10.1111/cen.13045.
7. The Neuroendocrine Effects of Traumatic Brain Injury, 2007, DOI: 10.1176/jnp. 2007.19.4.363
8. Brain damage, sex hormones and recovery: a new role for progesterone and estrogen? 2001, DOI: 10.1016/s0166-2236(00)01821-x.
9. Estrogen and progesterone as neuroprotective agents in the treatment of acute brain injuries, 2003, DOI: 10.1080/1363849031000095279.
10. Hypopituitarism after traumatic brain injury. 2005, DOI: 10.1530/eje.1.01895.
11. Physiology, Progesterone. 2021, StatPearls.
12. Physiological Action of Progesterone in Target Tissues, 1997, DOI: 10.1210/edrv.18.4.0308.
13. Endocrinology: An Integrated Approach. Whithead, 2001.
14. Physiology, Thyroid Hormone, 2021, StatPearls.
15. Mechanisms in Endocrinology: Insulin and type 1 diabetes: immune connections, 2013, DOI: 10.1530/EJE-12-0693.
16. Normal Physiology of Growth Hormone in Adults, 2019, Endotext.
17. The Hormone Solution, Hertoghe, 2002.
18. Vitamin D and the central nervous system, 2013, DOI: 10.1016/S1734-1140(13)71003-X.
19. Vitamin D and neurocognitive dysfunction: Preventing “D”ecline? 2008, DOI: 10.1016/j.mam.2008.05.001.
20. Physiology, Adrenocorticotropic Hormone (ACTH), 2020, StatPearls.
21. Pregnenolone, Henderson, DOI: 10.1210/jcem-10-4-455.
22. Mechanisms in Endocrinology: Estradiol as a male hormone, 2019, DOI: 10.1530/EJE-18-1000.
23. What Does Estrogen Do? 2014, DOI: 10.1210/jc.2014-v99i4-31A.
24. The Role of Estrogens in Control of Energy Balance and Glucose Homeostasis, 2013, DOI: 10.1210/er.2012-1055.
25. Relationship Between Testosterone Levels, Insulin Sensitivity, and Mitochondrial Function in Men, 2005, DOI: 10.2337/diacare.28.7.1636.
26. Revisiting the role of testosterone: Are we missing something?, 2017, DOI: 10.3909/riu0716.
27. The Biological Actions of Dehydroepiandrosterone Involves Multiple Receptors, 2008, DOI: 10.1080/03602530600569877.
28. Hypopituitarism After Multiple Concussions: A Retrospective Case Study in an Adolescent Male, 2007, PMID: 18060001.
29. Neuropsychology and clinical neuroscience of persistent post-concussive syndrome, 2008, DOI: 10.10170S135561770808017X.
30. Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury, 2006, DOI: 10.1089/neu.2006.23.928.
31. Neuroendocrine Dysfunction in a Young Athlete With Concussion A Case Report, 2017, DOI: 10.1097/JSM.0000000000000408.
32. GH deficiency as the most common pituitary defect after TBI: clinical implications, 2005, DOI: 10.1007/s11102-006-6047-z.
