Hormonal Imbalances — Causes, Consequences and Corrections

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

Hormones are a class of molecules that do not alone produce effects in the body, but instead are used to trigger other molecular effects by stimulating a wide variety of protein receptors. The word hormone is derived from the Greek hormao, meaning to arouse, or set in motion. Because of this relatively simple activity, many hormones are very similar in structure. This allows the body to easily transform one hormone into another as needed. A very complex system of feedback balance is therefore at the heart of hormone metabolism, and this is called the endocrine system. Endocrine (endo + krinein) simply means internal secretion, and this secretion of hormones occurs at a very large number of tissues in the body, not only at principal glands such as the adrenal, hypothalamic, pituitary, ovarian, testicular, and thyroid, but also from groups of cells in tissues throughout the body. Hormones are produced and secreted from our fat cells, from our bone marrow, from our organs, from breast tissue, etc., and local production and conversion of hormones is just as important as the systemic circulating levels that we commonly measure. Both systemic hormonal balance, and the balance in local tissues maintained by the balance of enzymes that convert hormones to active forms and other hormones, or rather control the rate of these conversions, as well as the balance of hormonal receptor types and their expression, outside and inside the cell membranes, are important to hormonal homeostasis. Explanations in standard medicine that describe these hormonal problems simply as estrogen deficiency or "Low T " do a disservice to the patient community that is trying to take a more proactive role in their hormonal imbalances and corrections. The first step in this process is greater patient understanding of their health problem.

The endocrine axis, called the adrenal-hypothalamic/pituitary axis, exerts a focal regulation of many systemic hormone levels, but involves an array of hormones whose job is to stimulate production of other hormones, maintaining a complex hormonal homeostasis via an array of feedback signals. The adrenal endocrine gland is part of the kidneys, and the hypothalamus and pituitary (hypophysis) are halves of a single gland or organ, located just below the thalamus, or main control center of the central nervous system, at the top of the brainstem. Both the adrenals (suprarenals) and the hypothalamus/pituitary are smaller than you may think, with the hypothalamus and pituitary about the size of 2 dried beans, and the suprarenals (adrenals) only about an inch and a half in height. The hypothalamus/pituitary gland has an hourglass shape, with the thinner belly of the gland holding an array of nerve axons and an arterial and veinous system that both connect and transport nutrients, protein messengers, and hormones to both the hypothalamic and pituitary sections of the gland. In fact, the posterior part of the pituitary is an extension of the neural axon array of the hypothalamus, and the insistence that these two brain nuclei are separate organs in separate systems in the body is at this point in time almost neurotic.

Many experts in the field actually now think of these systems as one, the neurohormonal system, and only our clinging to old ideas keeps us from achieving a more realistic and holistic view of our hormonal health. In 1961, the esteemed Dr. Jonas Salk gave a lecture to the Massachusetts Institute of Technology (MIT) that described this new and practical view at metabiology, and more than 50 years later standard medicine is still resisting his more holistic quantum view. The adrenals, or suprarenals, literally the top of the kidneys (renal glands), also are divided anatomically according to function, with the tissues known as the cortex (bark, or outer layer) and medulla (marrow, core - also a term for the spinal cord nerves), but each of these tissue groups has a strong neurological component, with the medulla part of the sympathetic aspect of the autonomic nervous system, and both the cortex and medulla reacting with inhibitory or excitatory hormonal effects to sympathetic nerve signals depending on the need of the body. As scientific research advances, our notions of hormonal production and holistic feedback balance becomes more and more complex. All of this knowledge of hormones and the widespread hormonally secreting cells brings us to the practical realization that hormonal health must be achieved through a holistic process, and helps us to realize that the failure of allopathic medicine to safely and effectively control our hormonal imbalances are tied to this fundamental principle. Simply substituting synthetic hormones for real hormones is not the best solution to restoring function to such a complex system, and in fact alters the quantum field of our hormones, our endocrine system, in progessively negative ways.

Hormonal health problems occur when particular hormonal levels in the body are not maintained within a physiologically normal, or optimum, rate of secretion and conversion in relation to other hormonal secretion rates. Maintaining endocrine function and balance is the key to hormonal health, not just filling the tank with a particular hormone. Substituting synthetic hormones leads to a decrease in the function of the hormonal glands that maintain this balance, and an inability to maintain normal hormonal production. Over time, this synthetic hormonal replacement alters even the genetic expression of hormone receptors, creating further dysfunction. Restoration of homeostatic endocrine function and balance is the optimum treatment strategy, and can be achieved with a more holistic approach in Complementary Medicine. More and more research is clarifying the effects of acupuncture, herbal nutrient medicine, bio-identical hormone therapy, and even deep tissue therapy to affect and restore the naturally programmed endocrine balance and function.

This does not mean that we are to abandon our current approaches with specific hormone therapies, but rather that we must expand our medical approaches to include Complementary and Integrative Medicine (CIM) and what it can contribute to the restoration of hormonal function and balance. Just as in cancer adjunct therapy, we must also utilize Complementary and Integrative Medicine to both restore natural endocrine function and alleviate and prevent the side effects that occur when we use synthetic hormone therapies. By using pharmacological hormones only when necessary, and taking a more realistic attitude toward what the public really sees as acceptable risks, we might realize that Complementary and Integrative Medicine holds much promise in this area of endocrine restoration and health.

Currently, the pharmaceutical approach to hormonal therapies involves use of synthetic variants or analogs to our natural hormones. The main reason for this strategy centers around the fact that our drug patenting process requires that we create a new chemical product if we are to get a patent. Naturally occurring hormones, found in simple molecules, often identical in plants and animals, cannot be patented. Potential for huge profit is thus removed when we utilize these bio-identical hormones. Choosing to utilize synthetic variants of our hormones to achieve particular goals in therapy is a sound approach when benefits outweigh risks. Many people have found this to be a simple solution to prevent pregnancy or to counter an acute severe inflammatory reaction, and short term use with low dose often poses few problem for hormonal health. Do not mistake this use of hormonal chemicals as a substitute for the actual process of balancing and restoring hormonal health. The failure of hormone replacement therapy and findings of unacceptable health risks should not be forgotten, and both the public and the medical doctors should, and are, finding that a new fundamental approach must be taken to restore hormonal balance and health with Complementary and Integrative Medicine. As with many types of therapeutic protocols in Complementary Medicine, this process may not be as simple as we would like it, but keep in mind that success with holistic medicine in restoration of hormonal balance and health will be lasting, and you will not be dependent on chronic use of the therapies. Bio-identical hormone therapies should not be used to replace natural human hormones, but rather to stimulate and reset normal production and balance that is programmed into our genetic code.

Adrenal insufficiency and cortisol imbalances may be driving a host of subclinical hormonal pathologies, such as subclinical hypothyroidism, hyperparathyroidism, hypothalamic insufficiency, and even neurodegenerative conditions

Adrenal insufficiency may be a primary or secondary disease. Standard allopathic medicine has always focused on the primary adrenal pathology, usually related to damage to the adrenal cortex in Addison's disease, cancer, autoimmune destruction, or tuberculosis. A much more prevalent disorder is adrenal insufficiency secondary to causes outside of the adrenal and pituitary, which often begins and advances slowly and subclinically (no apparent clinical symptoms, or red flags). Secondary adrenal insufficiency may give normal aldosterone and angiotensin levels on lab analysis, but diurnally low or fluctuating cortisol levels, and low ACTH (hypothalamic-pituitary function). It is important to test for a diurnal cortisol pattern, and use of the saliva metabolite tests is most appropriate for this analysis. Secondary adrenal insufficiency, when seen abruptly, is usually a result of abrupt withdrawal of steroid hormonal treatment, and even a short course of a corticosteroid may trigger hypothalamic dysfunction, causing the hypothalamus to alter its pattern of adrenal stimulation. Corticosteroids administered via inhalers, hypodermic injection into joint tissues, or topical use may result in secondary adrenal insufficiency with symptoms that persist for a year or more even after stopping the medication. Of course, patients who are overusing asthma corticosteroid inhalers and taking topical corticosteroid creams may encounter accumulation and dosing problems more readily, and be unaware of the potential problem. To see confirmation of this problem that is usually ignored by prescribing doctors, click here to see the respected Merck Manual explanation: http://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/adrenal-disorders/secondary-adrenal-insufficiency. Studies in the last decade have also found that a much higher percentage of the population experiences micro-tumors and lesions in the small hypothalamus-pituitary complex. These studies required autopsy exams, and this information was not available in the past, and does generally reflect the incidence in the older adult population. Functional deficiency of the hypothalamus-adrenal axis is still poorly studied or understood, though, and adrenal insufficiency can not be ruled out if there is no history of excess corticosteroid use, abrupt corticosteroid withdrawal, or evidence of clinical disease such as Addison's disease or panhypopituitarism.

Since the use of corticosteroid therapy is now increasingly prescribed for a number of disorders, without apparent concern as in the past, this is a big potential public health problem. The adrenal glands, or suprarenals (top of the kidneys), secrete a number of important hormones in a highly regulated and fluctuating manner, responding both to need and to diurnal patterns or hormonal, or neuroendocrine, metabolism. The two primary adrenal hormones are cortisol and aldosterone, which are very important to modulate responses to stress, maintain proper blood pressure, and regulate the metabolism of proteins, carbohydrates and fats, as well as the balance between sodium and potassium, and insulin and glucagon. Other important adrenal hormones include pregnenelone, progesterone, testosterone, estradiol, angiotensin, DHEAS, corticosterone, and estrone. All of these hormones are highly regulated by the hypothalamus/pituitary neurohormonal complex in the brain, and may easily convert from one hormone to another as needed. In addition, adrenal, or suprarenal, hormones stimulate and regulate the important kidney hormones renin and erythropoetin, which are important in controlling blood pressure and the production of both white blood cells and red blood cells in the bone marrow.

Signs and symptoms of adrenal insufficiency usually begin gradually and worsen insidiously, but may occur abruptly in secondary adrenal insufficiency. These symptoms may include unusual fatigue and muscle weakness, dizziness when rising (orthostatic hypotension), nausea, diarrhea, loss of appetite, abdominal pain, weight loss, craving for salty food, hair loss in the armpits, pubis, eyebrows, or lower legs, and dark pigmentation of the skin in areas such as the armpits, or generalized bronzing. Hypoglycemia, dehydration, depression, and other alarming signs may also indicate adrenal insufficiency. Tests may show mildly lowered sodium, potassium, cortisol, DHEAS, aldosterone and renin, and other nypothalamus-pituitary hormones may also be analyzed, such as TSH, prolactin, FSH, LH and ACTH. A mildly elevated white blood cell count may occur. A more definitive test for adrenal insufficiency is the SST (short synacthen test), or the ACTH stimulation test (cosyntropin test), which measures the ability of the adrenal glands to produce cortisol in response to ACTH. This test is rarely performed, unfortunately, and even when the test is negative, this still leaves open the possibility that the problem lies in the hypothalamic function instead of the adrenals.

As stated, most cases of secondary adrenal insufficiency are the result of pharmaceutical corticosteroid use. Corticosteroid, or glucocorticoid therapy, is used both in low and high dosage, internally, topically and with inhalers, and is usually just called a steroid. If adrenal insufficiency is suspected, all of these corticosteroid medications should be gradually reduced and discontinued to allow the hypothalamic-pituitary-adrenal axis to recover. Steroid treatment chronically suppresses the hypothalamic-pituitary-adrenal axis by supplanting it, and abrupt withdrawal can present significant problems for the patient. The strongest standard corticosteroid medication is Prednisone or Methylprednisolone (Medrol), which is given often in acute situations where inflammatory reactions and drug hyperactitivity reactions seem out of control, and even in chronic disorders such as arthritis, bursitis, tenosynovitis, rheumatic disease, psoriasis, dermatitis, asthma, allergic rhinitis, angioedema etc. In many cases, a short course of synthetic corticosteroid will reverse acute crises in emergency care. These synthetic corticosteroid medications are often withdrawn abruptly, rather than in a gradual decrease of dosage, despite the risk of developing a secondary adrenal insufficiency. The reasons for too abrupt withdrawal of corticosteroid medication may be due to patient noncompliance with therapeutic directions, or may be due to improper dosing withdrawal by the prescribing medical doctor. Prednisone withdrawal syndrome may result in acute severe hyperglycemia, loss of adrenal function, immune deficiency and a quick advance of opportunistic infection, diabetic retinopathy, and central nervous system disorder. Current guidelines call for gradual dose reduction whenever prednisone is prescribed for more than 7 days to avoid adrenal insufficiency and a withdrawal syndrome. Milder forms of corticosteroid withdrawal pathology may result in chronic adrenal insufficiency, though, often undiagnosed.

Many medical experts agree that adrenal insufficiency related to the increasing use of glucocorticoid medication, or corticosteroids, is now common. These corticosteroids were once reserved for serious rheumatoid conditions that did not respond to any other therapy, but now corticosteroids are seen in drugstore medications obtained without a prescription or guidance, and many patients may be taking multiple low dosage corticosteroid medications.

Many of these medications are taken as needed, as with asthma inhalers and topical steroid creams, and abrupt changes in dosage have a negative impact on the Hypothalamic-Pituitary-Adrenal Axis, or main systemic regulatory control of our endocrine balance. In 2011, Dr. Maria Magiakou M.D. and associates in endocrinology at the University of Athens Medical School, published a new online textbook in endocrine pathology (Endotext.org), and stated: "Primary and secondary adrenal insufficiency related to natural causes is uncommon, whereas iatrogenic, tertiary adrenal insufficiency caused by suppression of the Hypothalamic-Pituitary-Adrenal (HPA) function by glucocorticoid administration is common. Glucocorticoid treatment (e.g. Prednisone) may not suppress the HPA axis at all, or it may cause central suppression or complete adrenal gland atrophy. Supraphysiologic glucocorticoid doses inhibit both CRH (corticoid releasing hormone) production by the hypothalamus and ACTH production by the pituitary gland. When this inhibition lasts longer than the duration of the glucocorticoid exposure, it is called adrenal suppression. Since the introduction of glucocorticoids in the treatment of rheumatoid arthritis in 1949, the therapeutic applications of these drugs were greatly broadened to encompass a large number of nonendocrine and endocrine diseases. Long-term glucocorticoid use worldwide is estimated at between 1% and 3% of adults. The glucocorticoid-induced adrenal suppression, when glucocorticoids are used in supraphysiologic doses, renders the adrenal glands unable to generate sufficient cortisol if glucocorticoid treatment is abruptly stopped and the patient develops glucocorticoid deficiency manifestations." Of course, the long-term use of glucocorticoid therapy in the United States is much higher than the rest of the world, and this is presenting an alarming incidence of subclinical adrenal insufficiency in the U.S. population.

Glucocorticoid prescription has long been recognized as the most prevalent cause of secondary osteoporosis, and this is because the use of synthetic adrenal hormone cannot duplicate the complex diurnal rates of secretion of natural adrenal cortisone. Excess cortisone often results with use of synthetic cortisone medications, and synthetic medications do not duplicate all of the processess of natural adrenal hormones. Glucocorticoid use and adrenal insufficiency may play a significant role in the development of subclinical hypothyroidism and hyperparathyroidism as well, contributing to osteoporotic risk. Since hormonal health is a consequence of many parts of the hypothalamic-pituitary-adrenal axis, and the whole endocrine system, acting together in a complex systemic feedback mechanism, restoration of hormonal balance, rather than supplanting deficiencies with synthetic replacement, is a preferred method of promoting healthy function and avoiding adverse effects in the long term.

A number of therapeutic protocols in Complementary and Integrative Medicine (CIM) may address issues of adrenal insufficiency safely and effectively. Adrenal cortex bioidentical extract, PKA (pyridoxal alpha ketoglutarate), bioidentical pregnenelone topical cream, bioidentical progesterone topical cream, Ashwaghanda, Vitex, Siberian ginseng, L-tyrosine, L-arginine, P5P (active Vitamin B6), Calcium AEP, pantothenic acid, Maca, Magnesium-Potassium supplement, beta-escin (Horsechestnut extract), and phosphatidylserine have all shown positive benefits in scientific study, and to best utilize such therapies, a professional, such as a Licensed Acupuncturist and herbalist, or a Naturopathic Doctor, should be utilized. Combining acupuncture, and even deep tissue physiotherapy, or Tui Na, with the correct herbal and nutrient medicines in a step-by-step protocol, could yield much better outcomes.

Adrenal Fatigue Syndrome as a controversial and difficult diagnosis

For over a decade, many medical experts have focused on mild adrenal insufficiency, termed Adrenal Stress Syndrome or Disorder. This is believed to be caused by chronic physiological and mental stress combined with subclinical hormonal imbalance. Existing blood tests are now designed to show subclinical pathology, and so many medical doctors discount the existence of Chronic Adrenal Fatigue Syndrome. Many patients, on the other hand, have signs and symptoms of adrenal insufficiency, yet are not given a diagnosis, or explanation for their symptoms. This is of course frustrating. A thorough differential diagnostic workup should be performed, to rule out such diseases as Chronic Fatigue Syndrome, Fibromyalgia, etc., which the World Health Organization now combines in the term Chronic Encephalomyelitis, or Encephalomyelopathy, or even Depressive Mood Disorders, but when no other diagnosis is found, a diagnosis of exclusion may come to the conclusion that Adrenal Fatigue Syndrome is the cause of the signs and symptoms. While many standard medical doctors insist that treatment of Adrenal Fatigue Syndrome with Complementary Medicine may itself cause health problems, this is highly unlikely if the patient utilizes a professional Complementary Medicine physician such as a Licensed Acupuncturist and herbalist. This physician may have the patient test for a panel of active hormone metabolites, utilizing saliva and veinous blood samples, which is highly accurate today after decades of development, and so arrive at an objective assessment of overall hormonal balance and health. This is combined with the standard diagnosis in Traditional Chinese Medicine that uses empirical signs and symptoms to arrive at a holistic assessment of health and function. While there is some cause of concern for patients self-diagnosing and self-medicating in suspected cases of Adrenal Fatigue Syndrome, the obvious solution to this problem is to take the concerns seriously, and give patients an integrated approach, combining standard medicine with professional Complementary Medicine. The entire problem with the subject of Adrenal Fatigue Syndrome is that standard medicine has been loathe to utilize such Integrative Medicine. If professional treatment protocols in Complementary Medicine show progress in improving the signs and symptoms of suspected Adrenal Fatigue Syndrome, then this diagnosis of exclusion was probably correct. Such logic is hard to argue.

Hypopituitarism, an Often Overlooked and Underdiagnosed Cause of Testosterone Deficiency and Adrenal Deficiency

Hypopituitarism, or Pan Hypopituitarism, is a complex and poorly understood disorder of decreased secretion of one or more of the 8 essential hormones, or neurohormones, normally produced in the pituitary gland of the brain. The hypothalamus and pituitary compose the central command center of the endocrine system and work closely with the adrenal glands of the kidneys to create neuroendocrine regulation via a feedback system that is in constant flux. Few studies have explored the incidence of hypopituitarism in the population, but one published study in Spain found that 45.5 people out of every 100,000 have been diagnosed with hypopituitarism, as determined by hospital records in Europe. This study reflects only those for whom no other diagnosis was found in more severe cases of neuroendocrine disease, though, and the actual incidence of hypopituitarism is thought to be much higher. This disorder is rarely considered because standard medicine still considers only pituitary tumors, brain trauma, and other types of brainstem lesion as a cause, which are considered rare. Autopsy studies in the recent decades, though, reveal that small tumors and lesions of the pituitary are fairly common, especially with aging, and almost always overlooked. In addition, a variety of causes and factors could affect the function of the hypothalamus, the neurological control of the pituitary gland. The manifestation of hypopituitarism is extremely varied, as well, with insufficiency of any of the 8 pituitary hormones potentially isolated, or any combination, and most of these pituitary hormones are hormones the stimulate and regulate the secretion of other hormones, making a diagnostic workup difficult to assess. In addition, there is still very little treatment for hypopituitarism in standard medicine, and when this is the case, there is always little motivation to test and diagnose the condition. On the other hand, Complementary and Integrative Medicine (CIM) has thoroughly explored treatment options for restoration of the hypothalamus pituitary complex, and each year more and more evidenced therapeutic tools are revealed and evidenced, including specific acupuncture stimulation, herbal and nutrient medicines. Use of bioidentical pregnenelone cream, Calcium AEP, bioidentical adrenal cortex extract, PKA, Vitex, and other nutrient and herbal medicines, especially combines with studied electroacupuncture treatments, provides a safe and effective strategy to restore hypopituitarism, and potentially to help the body resolve lesions and microtumors affecting this brain center.

The Increasing Diagnosis of Testosterone Deficiency and use of chronic testosterone replacement may be just plain wrong - A Diagnostic Sign, such as Testosterone Deficiency, is not a Diagnosis, and a thorough Diagnostic Workup is Needed to Evaluate

The number of advertisements for testosterone and prescriptions for testosterone in 2013 are now immense, but the use of testosterone replacement is not a simple matter of just supplementing a deficiency. This oversimplification will have dramatic consequences for many patients in the long term. A 2012 review of low testosterone findings, typically called male hypogonadism, by the esteemed Cleveland Clinic, published in the Cleveland Clinic Journal of Medicine (cited and linked below in Information Resources), shows that there are many potential causes of low testosterone, and treating this problem as if it were just normal aging, or even just a choice between simple primary or secondary hypogonadism is a profound mistake. The intelligent patient will pursue the real diagnosis that is producing this diagnostic sign of low testosterone, so that these underlying health problems can be addressed. To ignore underlying health problems and just take some testosterone could be a big mistake.

In the diagnostic workup, patients need to consider the whole health history, and especially the most pertinent facts, such as whether the testosterone deficiency came on suddenly or gradually, whether it followed an illness or the taking of a medication, especially a glucocorticoid like Prednisone. The full standard diagnostic workup is detailed below in the Cleveland Clinic article. A number of considerations, such as toxin accumulation, receptor mutation, insulin resistance, iron overload toxicity, dopamine imbalances, subclinical hypothyroidism, radiation exposure, chronic inflammation, etc. are not addressed very well in standard medicine, but a knowledgable Complementary Medicine physician may help clear these problems, and the choice of a competent Licensed Acupuncturist and herbalist, or Naturopathic physician, as part of the team, is very sensible. A link below to the diagnostic guidelines of the Center for Andrology and Sexual Medicine at the famed Karolinska University and Karolinska Institute, in Stockholm, Sweden (see link below) shows that a majority of men with low testosterone do not show a classic endocrine pathology, but rather present with associated diseases such as Metabolic Syndrome, diabetes, cardiovascular disease, COPD, and chronic low-grade infections and inflammatory diseases. Ignoring this fact, and just thinking that the testosterone in the tank is low may lead to a very poor long-term outcome.

Testosterone therapy for women is increasingly seen as well in recent years. In 2005, an expert on perimenopause and hormonal pathologies, Dr. Alessandra Graziottin of the University of Florence, Italy, stated that: "It has been reported that in contrast to the 50 percent of women who report severe symptoms following natural menopause, about 90 percent experience severe symptoms following surgical menopause (hysterectomy and/or ovarectomy), in which a primary source of androgens has been removed." (The Journal of Sexual Medicine 2005; 2.suppl.3; 133-145)

Dr. Graziottin states that women who have undergone chemotherapy or radiation treatment that destroys follicles and Leydig cells in the ovaries irreversibly, or iatrogenic menopause, also report a higher degree of severe symptoms of hormonal dysfunction, and are often unrecognized in standard medicine. Women who have undergone surgical or iatrogenic menopause also have a much higher rate of sexual desire disorder and distress than women undergoing natural menopause, due to the removal of a primary source of testosterone or androgens. She states that levels of testosterone and proandrogens in women during reproductive years exceeds that of estradiol by several-fold to several thousand-fold, and that about half of this circulating testosterone is secreted directly by the ovarian stroma and adrenal zona fasciculata in roughly equal quantities. For women in their reproductive years, the levels of testosterone on average are about equal to men, adjusted for age, but will fluctuate within the monthly cycle more radically. This is in contrast to the popular notion that has been promoted that men are driven by large testosterone levels while women have low levels of testosterone and are thus more passive in nature. This fantasy is driven by social bias, not scientific fact. After menopause, the contribution of testosterone production by the ovaries rises dramatically, according to Dr. Graziottin, from under 30 percent of the total, to over 50 percent. The popular notion that the ovaries cease to function after menopause is also completely false, and the advice to many women in the past to just remove the uterus and ovaries sexually to avoid health complications was completely wrong.

Unfortunately, just as with hormonal therapy for men, testosterone therapy for women often proceeds not with a restorative and holistic approach, but with a simple prescription for testosterone, especially now that topical delivery of testosterone is readily available. While this simplistic therapy, utilizing testosterone to improve sexual desire and pleasure, may be effective in the short run, it is often problematic. The second route of treatment, adding testosterone to hormone replacement drugs, may also be problematic, and often this new approach is now a sales technique to convince women that are wary of synthetic hormone replacement to opt for this pharmacological approach, just as the new forms of synthetic hormonal birth control were sold to skeptical women by telling them that they would clear up their acne, even when the young women had no noticeable acne problem. While it is true that estrogen deficiency leads to thinning of the membranes in the sexual organs and a reduced overall blood flow and vasocongestion with sexual activity, restoration of the entire hormonal feedback cycle and regulation, not just replacement of estradiol and testosterone, will result in a better overall state of health as well as a better overall sexual physiology.

By ignoring the underlying causes of low testosterone when treating testosterone deficiency, the physicians and patients leave open the possibility that 1) the treatment will not work, 2) the underlying health problems will get worse and threaten the patient, and 3) long term use of the testosterone replacement will have an adverse effect. Adverse effects include not only prostate pathologies and thick blood, or blood dyscrasia, but an array of complex hormonal and metabolic imbalances caused by use of hormone replacement. Treating the whole person, and all of the underlying and contributing health problems, restores health and prevents future health problems.

The array of causes of hormonal pathologies and the widespread incidence in the population in recent decades

An April 1, 2012 New York Times Magazine article, entitled The Incredible Shrinking Childhood, outlined the evidence on hormonal changes in the children of the United States, with puberty occurring years earlier for a significant percentage of children.

While a number of clinics, such as University of California San Francisco Benioff Children's Hospital, Cinncinati Children's Hospital, and the Duke University Medical Center, have noted that an alarming number of 6 to 9 year old girls are showing signs of hormonal stimulation of breast growth and pubic hair, as well as psychological changes related to hormonal stimulation, and earlier menarche, there is no consensus on specific explanations. Studies of early hormonal changes in children started in earnest at Duke University Medical Center, where Marica Herman-Gidddens, a physician's assistant, or PA, in the pediatric clinic, noted earlier than normal signs of puberty and started collecting data. By 1997, her research sampled 17,000 girl's records and noted that the average age of breast growth was at least a year earlier than normal. While the average age of first menstruation, or menarche, has only lowered by about 4-5 months from normal, these statistics are driven by a large number of young girls now having their first menstruation at age 9 to 10. Parents are frustrated, as standard medicine has little to offer in treatment, except synthetic hormonal drugs that most consider too risky for children, with more health problems generated than cure. Increasingly, as this article points out, mothers are researching online to find alternative treatments, but this itself presents a confusing and frustrating set of claims with little true individualized medical guidance.

The various pediatric neuroendocrine experts cited in this New York Times Magazine article suggest that abnormal hormonal stimulation in the population is occurring due to a variety of factors associated with the world that we have created with modern science. Chemicals such as BPA in soft plastics, PBB in flame retardants, and an array of chemicals used in pesticides, herbicides and manufacturing, as well as common household cleaners, are known xenoestrogens, or xenohormones, or chemical mimics of human hormones. Childhood obesity, or hormonal changes in the fat cells, organs and brain that causes resistance to the hormones insulin and leptin, are also driven by new sugars and fats, such as high-fructose corn syrup and transfats, as well as glutamates increasingly used to stimulate an addiction to processed foods. Societal stressors, such as poverty, divorce and drug addiction, are also found to be associated with childhood stress and abnormal hormonal changes. Researchers such as Bruce Ellis, a professor of human development at the University of Arizona, published research in 2011 that showed that measurable signs of stress in children, such as raised cortisol levels, pulse and respiratory rates, were associated with early puberty. Julia Graber, associate chairwoman of psychology at the University fo Florida, notes that research has linked higher rates of depression and anxiety to early development and menarche, often continuing on into the early 30's for girls with earlier puberty. Not only estrogen, which drives early menstruation, but androgens, which are primarily responsible for early growth of pubic hair, and an array of associated hormones of the hypothalamus and pituitary, are implicated, and these affect neurotransmitters and neuroendocrine cell receptors as well. The array of causes of hormonal pathology are truly daunting.

Clearly, a holistic approach is needed to reverse these hormonal changes and pathologies, not only associated with earlier childhood development, but with the whole population, especially women, where hormonal abnormalities more easily disrupt life that revolves around a monthly cycle of hormonal changes related to fertility. Standard medicine continues to look for specific allopathic treatments, a path that will yield poor results overall, and consequently the standard research continues to look for specific causes that these drug treatments may address. Increasingly, the population is looking at a bigger picture. More and more attention is finally being paid to health and wellness, not to chemical alterations, and a holistic approach that addresses the environment, diet, lifestyle, and Complementary Medicine is being explored.

Hormone physiology and understanding of our hormonal health

Hormones comprise a class of signaling molecules that both circulate to target distal organ receptors and exert local effects. This class of simple signaling molecules includes diverse chemical types, including steroid, protein (e.g. insuline and growth hormones), peptide, amino acid (e.g. thyroid and melatonin), and eicosanoids (derived from omega-3 and 6 essential fatty acids). Steroid and eicosanoid hormones are lipid soluble, while protein, peptide and amino acid hormones are water soluble. The lipid soluble steroids and eicosanoids must bond to glycoprotein carriers in the blood, forming ligand-protein complexes to keep them from breaking down in the bloodstream and to carry them to targeted receptors. Many hormones may be stored in tissues, and most hormones can be converted to another type of hormone, or to an active form of the hormone, in local tissues, as needed. All of this requires a complex field of metabolism to work properly, as well as a feedback mechanism to determine levels and concentrations. In the prevalent homeostatic negative feedback control mechanism, the higher concentration of a hormone alone does not determine the rate of production and excretion, but a number of factors control this balance, with a primary emphasis on the level of the effect of the hormone, not the actual concentration or circulating blood level. For this reason, we now have tests that measure the active metabolites of the hormone with simple and inexpensive saliva and veinous blood samples. Hormone production and secretion can also be stimulated and inhibited by neurons, autonomic signals, concentrations of nutrients and mineral ions, concentrations of the binding glycoprotein carriers, and even environmental changes, especially changes in light, temperature, and seasonal changes. For most protein, peptide and amino acid hormones, the interaction occurs at a receptor on the cell membrane, while most steroid and thyroid hormones interact with receptors on the inside of the cell, at nuclear receptors that trigger genetic transcription factors. They can bind to receptors in the nucleus of the cell because they are lipid soluble and thus can more easily cross the lipid membrane of the cell. As always, though, no rule is without exceptions, and many steroid hormones attach to receptors on the outside of the cell membrane, or the plasma membrane. Originally, we set up a system whereby our hormones are defined by function, not structure, though, and we generally cling to this definition in medicine despite the fact that each year our research uncovers more and more diverse functions for each hormone, and more and more diversity in the chemical structures of hormone types that are classified according to primary function.

Steroid hormones have been the subject of greatest interest to our hormonal problems in life. Steroids are a large family of chemical substances, comprising many hormones, body constituents, and drugs, all of which are built upon a particular chemical skeleton, composed of cyclic rings. Most of the steroid molecules are isomers, meaning that they exist as multiple forms that are identical with respect to the composition of parts, but that the position of these parts, or atoms, on the ring structure of the molecule, is different. This slight difference in structure is what the receptors react to, and hence different receptors are triggered in different ways by these slight variances between our hormones. Our endocrine system also is able to achieve easy transformation of one steroid isomer hormone into another as needed to insure bioavailability in our body. The most well known steroid hormones are the estrogens, progesterone, testosterone, corticosterone, cortisol, and aldosterone. Steroid hormones are all derived from cholesterol, and with the aid of various protein enzymes convert easily one into another. For this reason, a healthy cholesterol metabolism and bioavailability of the hormones that are normally precursors to the other steroid hormones are vital to restoration of hormonal health.

Cholesterol is an abundant steroid hormone, or sterol (steroid with an alcohol attached), with a large side-chain of hydroxyls that is removed to make our more well known steroid hormones. The normal chain of production of our steroid hormones starts with cholesterol turning into pregnenelone, and pregnenelone into progesterone or DHEA (dehydroepiandrosterone). Next we see progesterone turning into cortisol, aldosterone, estrone, or testosterone, and finally, both estrone or testosterone into estradiol as needed in the body. By observing this chain of steroid transformation, we see the importance of healthy cholesterol, pregnenelone and progesterone as building blocks for the production of the key pathological steroid hormones, estradiol and testosterone. Testosterone also turns into dihydrotestosterone, which is the form that activates many receptors linked to such problems as balding and prostate cancer and hypertrophy.

When we take a holistic approach to hormonal health, one aspect that we must consider, therefore, is the bioavailability of healthy cholesterols, pregnenelone and progesterone. When all of these are healthy, the chance of restoration of hormonal imbalance is greatly improved. This basic treatment protocol therefore involves improved quality of fats, the building blocks of lipid cholesterol, improved liver function, the site of most cholesterol production, clearing and regulation, and the controlled use of topical bioidentical hormone creams containing pregnenelone and progesterone production stimulators. Various herbal formulas and nutritional supplements are combined in this type of treatment, and acupuncture is an effective symbiotic therapy to help the body respond better to these nutritional therapies. The various herbs, supplements and bioidentical hormones mentioned here are extremely safe, and work very well when prescribed in the right way by a professional herbalist and knowledgeable Complementary Medicine physician, such as a Licensed Acupuncturist.

Misunderstandings of the cholesterol metabolism, and cholesterol as the fundamental building block of hormonal health

The exact same cholesterol molecule is found in all of our lipoproteins, the LDL (low density), HDL (high density) etc. that are commonly, and mistakenly, called our bad and good cholesterols, for our lipoproteins are not cholesterol, but merely contain cholesterol, and there are only two types of cholesterol, the normal healthy type, and the misshapen type that is removed and broken down by our liver. The lipoproteins, which are measured on our lab tests, are differentiated by types that primarily carry lipid, or fatty, molecules like cholesterol and triglycerides, to and from our liver. The LDL (low density lipoproteins) transport cholesterol out from the liver, the HDL (high density lipoproteins) transport old or misshapen cholesterol to the liver for excretion in the bile, and the VLDL (very low density lipoproteins) transport triglycerides from the liver and intestine to the fat cells for storage. Each of these lipoprotein types also carry other lipid molecules, and each carries cholesterol and apolar amino acids. The density of the lipoprotein is determined by the amount of protein (apolipoprotein), with HDL being made up of about 50% protein.

There are many misconceptions surrounding our cholesterol. Number one, that our cholesterol levels are bad if too high, and that our cholesterol levels are a product of our diet. In our body, cholesterol is very tightly regulated. If we eat more cholesterol, our bodies produce less, so that the right levels of cholesterol are maintained for our needs. When the cholesterol is of poor quality, the body removes it and turns it into bile, triggering increased production of more healthy cholesterol. What we measure on circulating blood tests are the circulating levels of lipoproteins, which are both carriers in our blood of cholesterol and other metabolites, and important constituents of our cellular and other membranes, such as the myelin sheaths on our nerves. The lipoproteins that attach to, or make up membranes, utilize cholesterol as a hormone that opens channels for transport through the membranes. It is true that high low density lipoproteins are associated with atherosclerotic plaque and increased risk of cardiovascular disease, but more exact research has found that this high LDL association may not be the actual cause of the atherosclerotic plaque, and that other associative markers, such as C-reactive protein and homocysteine levels are more accurate indicators of cardiovascular risk. Once we understand some of this important biochemistry, we see that blocking of production of cholesterol may not be such a good idea.

This lead us to the second common misconception, which is that cholesterol creates atherosclerotic plaque. While lipoproteins and cholesterol may accumulate in the atherosclerotic plaque, we have found over decades of research, that the real culprits in this disease are blood vessel inflammation and the attachment of both inflammatory regulating macrophages and various clotting factors to the sites of inflammatory damage. Clotting factors accumulate at sites of arterial vessel damage, to repair these sites. Our bodies are supposed to be able to clean out the clotting factors and fibers that repair the vessel, but when there is a type of dysfunction, the repair and elimination of plaque is hindered. When this healthy repair of arterial vessels is hindered, the atherosclerotic plaque continues to grow, until it narrows the artery, or worse, breaks off and travels to a narrow part or the artery, causing a blockage of blood flow that we call a stroke with an embolism. When these plaques around the inflamed areas of our vessels get too big, lipoproteins with cholesterol also attach, because lipoproteins are normal constituents of membranes. The approach to treatment of atherosclerotic plaque in Complementary Medicine is to aid the body in the task of maintaining healthy vessels and repairing the sites of atherosclerotic buildup. The treatment protocol with statin drugs is to mildly decrease one of the components of the arterial plaque, but this does not address the real problem.

Cholesterol controlling drugs, called statins, work by inhibiting the genetic expression of protein enzymes that are needed to create new healthy cholesterol. They also stimulate increased production of LDL (low density lipoprotein) receptors in the liver that remove cholesterol from the circulation. The increased need for LDL receptors reflects the deficiency of cholesterol that is available, but the same need of the liver cells for cholesterol to function properly. While these drugs have some modest effect on reducing production of cholesterol, the process is not a healthy process. Depriving the cells of cholesterol and increasing the need for cholesterol (LDL) receptors adds stress to the liver function. Decreasing circulating cholesterol, which is tightly regulated according to need of our cells and membranes, also produces potential health problems. The statins also do more than just target specific protein enzymes. The common side effects of statins involve pathological breakdown of skeletal muscle (rhabdomyolysis), decrease in the ubiquitous antioxidant CoQ10, decrease in the production of Vitamin D3 hormone, derangement of liver enzymes, inducement of other genetic expressions, such as atrogin-1, which also promotes muscle fiber damage, and inhibition of creatine kinase (CK), an important enzyme in the creation of ATP, the fuel for muscle contraction. If these problems with muscle metabolism become too great, the muscles start to break down, releasing excess creatine kinase from this process, creating a condition of elevated blood CPK, which may be mistaken for the autoimmune disorder dermatomyositis, and often takes a long time to resolve. While these problems only reach critical levels in a small percentage of patients, the processes are working to some extent in all patients. These side effects potentially create accumulative negative health effects over time, including muscle pain, joint pain, kidney stress, and increased accumulation of antioxidants and protein fragments in our tissues. They may also contribute to unhealthy myelin sheaths and neuropathy. Besides these accumulative side effects, the chronic use of statins is also alarming to many researchers and medical doctors, because they block production of healthy cholesterols, the building blocks of all of our steroid hormones.

A third cholesterol misconception is that the levels of cholesterol within our HDL (high density lipoproteins) is not that important. Chronic use of statin drugs may inhibit total lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C), but the deleterious effects on high-density lipoprotein cholesterol (HDL-C) that accompanies this process is not a healthy outcome. Studies have shown that decrease in HDL cholesterol is highly associated with deficiency of steroid hormone binding globulin (SHBG), which is a blood transport protein for testosterone and estradiol. Concentration of SHBG, like all hormonal metabolism, is regulated by a feedback mechanism controlled by levels of testosterone and estradiol. Studies of long-term adverse effects of synthetic testosterone or estradiol hormone replacement show that levels of beneficial HDL decline with this use, and we can see why. SHBG is also, like HDL cholesterol, produced and secreted mainly by the liver, and increased liver stress from long-term use of statin drugs, especially when combined with too many other pharmaceuticals, may impact liver production. During menopause, this steroid hormone binding globulin SHBG decreases considerably in many women. The result is that there is less circulating testosterone and estradiol, and the body responds by producing more testosterone and estradiol in the adrenal glands, leading to increased adrenal stress along with the lower circulating testosterone and estradiol. When HDL cholesterol levels are also low, this problem could be even worse, since low HDL cholesterol is associated with deficiency of SHBG. What we see on active hormone metabolite tests with these patients are cortisol levels that do not react as well as we need during the day, but then overact in the evening and at night, contributing to night sweats, heat flush and insomnia. Cortisol is a primary adrenal hormone, and with increased adrenal stress the diurnal cortisol rhythm is upset. We thus need to maintain a healthy level of HDL cholesterol, especially when we go through periods of hormonal deficiency, as in menopause. To confirm these facts, refer to the study cited below in additional information.

The fourth misconception concerning cholesterol lowering drugs that has emerged with recent studies, and is a cause of much concern in Washington, is that lowering cholesterol levels with these drugs actually reduces the risk of heart attack and strokes. Studies have shown significant lowering of LDL lipoproteins, yet have not shown significant reduction of cardiovascular events. On the surface, it is assumed that lowering of cholesterol with statin drugs provides significant prevention of cardiovascular disease and atherosclerosis, but a more detailed assessment results in questions concerning benefit, and with so much research revealing healthy ways to lower high cholesterol, with a little exercise, improved diet, and the taking of the correct herbal and nutrient medicine, there is now little reason to resort to statin drugs, which may have a deleterious effect on neurohormonal health. To read more on the questions concerning cholesterol and statin drugs, go to the article on this website entitled Cholesterol and Lipid Imbalance, and keep in mind that cholesterol is the most abundant hormone in the human metabolism, not a harmful chemical.

Cholesterol-lowering statin drugs thus have a number of potentially negative consequences concerning hormonal health, as well as both short-term and long-term adverse health effects that are often overlooked or downplayed. Statin drugs now carry FDA warnings that adverse effects on short-term memory and attention span, mental confusion, high blood sugar, and risks for diabetes may occur with long-term use.

A long-term study called JUPITER, and a follow-up meta-review of scientific study by Harvard Medical School and the Joslin Diabetes Center in 2012, found that the risk of advancing to type 2 diabetes from Metabolic Syndrome associated with statin drug use was increased 25 percent. Common short-term statin side effects include muscle pain, fatigue, insomnia, drowsiness, gastrointestinal discomfort and dysfunction, and irritable bowel. A 2013 study at Duke University found that patients with Metabolic Syndrome and obesity have the positive effects of aerobic exercise blocked when taking statin drugs. In a randomized clinical trial, those patients not taking statins improved the health of the heart muscle, cardiorespiratory fitness, and skeletal muscle fitness and function considerably with 12 weeks of a fitness routine, but these patients taking statin drugs instead of the placebo had almost no benefits from the aerobic fitness program. A 2012 study at the University of California in San Diego found a significant association of fatigue with chronic statin use, and this should come as no surprise when looking at how these drugs work. All of this stress with long-term use does not help aging patients with their hormonal health, as well as inhibiting the building block of steroid hormones, healthy cholesterol, and directly inhibiting the production of the hormone Vitamin D3, which is shown to be a very important hormone.

Hormone receptors and their role in a healthy hormone metabolism

Unlike our hormones, the protein receptors that react to hormones can be complex. These receptors react not only to hormones, but to neurotransmitters, and to antigens. Antigens are any substance that triggers an immune response, or a hypersensitivity response, and which reacts to antibodies or other immune cells. We thus see an intrinsic connection in the endocrine system to our neurological system and our immune system. In fact, many of our neurotransmitters, such as serotonin, also function as hormones. Our hormonal health depends upon optimal function of all three systems, the endocrine, immune and central nervous systems. A growing interest in such holistic fields of study as psychoneuroimmunology shows that we can no longer treat these systems as distinct entities when devising treatment protocols. The fact that hormone receptors react to antigens also means that accumulations of environmental toxins, which often trigger an antigenic response, may play a significant role in our hormonal imbalances. For example, inflammatory cytokines have been shown to affect the expression of estrogen receptors, and estrogens have been shown to reduce the overexpression of key inflammatory cytokines involved in chronic autoimmune inflammatory diseases, such as TNF-alpha, IL-6 and IL-1. Bacterial endotoxins have been shown to stimulate a chronic overexpression of these same problematic cytokines. Hormonal health and balance is integrally tied to immune health, and the health of the immune barrier in the intestines is integrally tied to hormonal health.

Synthetic hormones, and hormonal drugs such as Tamoxifen and Lupron, are proven to significantly alter the expression of our hormone receptors. In 2003, experts at the Division for Reproductive Technology at Karolinksa Hospital in Stockholm, Sweden tested laboratory animals with their ovaries removed for changes in hormone receptor expression when given hormone replacement therapy (medroxyprogesterone acetate, conjugated equine estrogens, or a combination of the two), or tamoxifen. These experts stated that until this time, there were no significant studies of these changes in hormone receptor expression published, despite widespread use of such drugs. The findings clearly showed that the hormone replacement therapies down-regulated progesterone receptors in the superficial glands, but increased expression of progesterone receptors in the stroma (connective tissue of organs), and decreased the variation between progesterone receptor types A and B, which are balanced normally to control rates of cell apoptosis, or cell life and death cycles. Hormone replacement therapy also decreased androgen receptors in the outer tissue of glands, but allowed expression of these receptors in the stroma, or connective tissues. Tamoxifen eliminated these androgen receptors in glands and stroma, and increased the progesterone receptor type B in the stroma.

Overall, these hormonal therapies created an imbalance of progesterone receptor types A and B in the uterus endometrium, which contributed to longer cell life, or less control of cell apoptosis (programmed cell death), resulting in increased risk of cancerous mutations. In addition, the regulation of these effects by androgens was decreased or eliminated with these drug therapies (PMID: 12646074). Prior study at the Karolinska Hospital in 2002 also found that these drugs adversely affected the balance of estrogen receptor types A and B, downregulating the type A receptor expresssions in the outer tissues of endocrine glands, but increasing it in the connective tissues, and increasing the ration of Type B (beta) to Type A (alpha) estrogen receptors in both the outer tissue of endocrine glands and the connective tissue, or stroma (PMID: 12475378). Also in 2002, at the Virginia-Maryland Regional College of Veterinary Medicine, in Blacksburg, Virginia, scientists showed that these synthetic hormones in hormone replacement therapies up-regulated the expression of the protein enzyme telomerase via telomerase RNA in the endometrial tissue cells, also increasing the risk of endometrial cancer (PMID: 11872219). These findings clearly explained why the use of these hormonal drug therapies increased the incidence of uterine cancers, and many other adverse hormonal effects, both in the short-term and the long-term. Despite these clear findings, synthetic hormone drugs and hormone-ablation and altering therapies continue to be promoted as sensible therapies in standard practice of gynecology and oncology, with little acceptance yet of hormonal restorative therapies.

We see from numerous studies that hormonal receptors are found on a large variety of cells in the body, with hormones exerting significant effects on the immune cells and the expression of both pro- and anti-inflammatory cytokines, and on cells of the autonomic nervous system, as well as neurons and support cells of the central nervous system. Studies also tell us that these receptors are stimulated by immune cytokines and neurotransmitters. Often, the types of receptors expressed modulates functional aspects of hormonal modulation. For instance, there are two types of estrogen receptors, alpha and beta, and the imbalance of expression of one type over another is integrally tied to breast cancer. Research has shown how overexpression of one type of receptor inhibits the natural apoptotic, or programmed cell death cycle, of breast cells, allowing some cells to live abnormally long lives and be subject to increased mutations that eventually result in cancerous growth. Not just estrogen in general, but an array of factors are involved in the normalization of estrogen receptor balance, and the complexity of this process that the body has evolved is enormous. Imbalances in inflammatory cytokines, neurotransmitters such as serotonin, metabolic chemicals that affect local transformations of hormones, and the balance of a variety of hormones in the local tissues and circulation all have significant effects on the balance of hormone receptor expression and the effects of the local hormones on cell receptors. This complexity makes the strategy of an allopathic specific chemical mediator as a complete therapeutic protocol insufficient. Patient and physician needs to utilize Integrative and Complementary Medicine to restore normal and healthy homeostatic balance in all of these systems to insure the best outcome.

Drugs may also affect our hormone balance and hormone receptors. For example, estrogen and prolactin are hormones that have a reciprocal endocrinologic relationship, meaning that levels of one will alter the levels of the other. There are many known drug causes of prolactin abnormalities. Narcotics, diet pills, appetite suppressants, cough and cold formulas, and benzodiazepines, prescribed for anxiety and depression, all have been studies and found to have prolactin altering effects. The now banned Phen-fen diet drug was also found to have long-term prolactin altering effects, and misuse of this drug that was derived from the active ingredients in the herb ephedrine, may still be effecting patients that were given this drug by their M.D. The common pesticide MTX has been found to alter prolactin secretion. Synthetic estradiol benzoate in hormone replacement therapy was found to have a dramatic effect. Common antidepressants and other drugs which have an affect on catecholamines such as dopamine and norepinephrine were also found to have dramatic effects on prolactin levels. Prolactin is a hormone rarely tested in hormone pathologies, yet a number of drugs and chemicals are known to affect levels by competing at hormone receptor sites, and this has a direct reciprocal relationship to chronic estrogen deficiencies.

Research by Robert W. McMurray, at the University fo Misissippi Medical Center Rheumatology Section, found that both estrogen and prolactin had possible pleiotropic effects on the immune system, also. This means that they potentially have similar effects to immune modulators, related to a single allele, or gene mutation, that is usually unrelated. If an allele, one of the pair of genes needed to effect gene expression, is mutated, either by inherited trait, or by the mutating effects of environmental toxins, drug side effects, or chronic inflammatory processes, the expression of prolactin, or the estrogens, can produce health problems related to immune response. In these cases, the symptom presentation is complex, and diagnosis is often overlooked. Effects on prolactin, as we have shown, may also have reciprocal effects on estrogens, and trigger these unwanted immune responses, such as autoimmune disorders, which include rheumatoid arthritis and other chronic painful conditions. We see that various potential problems that could affect our hormonal system in ways that are confusing to us and to our doctors, and that this could explain why some of us acquire autoimmune disorders. To treat these hormonally related immune problems we must consider a number of treatment protocols, including reducing the potential drug side effects, clearing food allergy related antigens, antioxidant therapy to reduce genetic mutations, etc. These therapeutic protocols can seem confusing and excessive at first, but with some education the patient can realize the logic to this approach, and embrace Complementary Medicine.

There is no single 'silver bullet' in this therapy of hormonal balancing. Instead, there are a lot of choices to consider and incorporate into the right protocol for the individual. The patient needs to find a knowledgeable Complementary Med physician or integrative physicians to guide them along this course. The TCM physician, or Licensed Acupuncturist, may provide this knowledge along with herbal protocols, acupuncture, dietary supplements and counseling on diet and lifestyle changes, and integrate with your Medical Doctor. The key in integrative therapy is to choose a doctor has adopted an open mind, and has taken the time to explore current research.

Psychoneuroimmunology, Neurohormonal Immunology, Mind-Body Medicine and the Emerging Field of Neurohormonal Study

The field of psychoneuroimmunology may have started with the historic 1961 lecture by Jonas Salk at the Massachusetts Institute of Technology (MIT), entitled Biology in the Future, and was later carried on by the renowned Dr. Robert Ader, who proved that physical health parameters did change with mood, and that there was a measurable mind-body interrelationship. In this and subsequent lectures Dr. Salk, the renowned pioneer of the polio vaccine, and the use of deactivated pathogens in vaccinology, as well as the founder of the more holistic and humanistic pioneering Salk Institute, one of the creators of the MacArthur Fellowship Program, and the Jonas Salk Foundation, outlined his research into the interrelationships between the genetic system, the immune system, and the nervous system, as well as cognitive and behavioral aspects that affected these. He included this study as part of what he called metabiology. This pioneering and holistic view was derided and attacked in standard biological sciences for decades, but is now emerging as perhaps the premier overall field in future medical care. We clearly see now that we have genetic mapping, functional MRI imaging to follow brain activity and its relation to therapeutic protocols, and many other new technologies that finally allow us to clearly see the expression of cell receptors that react to multiple chemical mediators within a field of these modulators, that Dr. Salk was indeed correct in his theories. Our cell receptors often respond to hormones, neurotransmitters, and immune cytokines, and do so in a quantum field of effects that depend on the balance of these chemicals at the receptor site, and an array of factors that determine the gene expressions of protein neurohormones and cell receptors. We have known for a long time that there is a close relationship between our nervous system and our hormonal, or endocrine, system, since the axis of feedback control resides in the hypothalamus-pituitary complex, and the adrenal portion of the kidney produces both key hormones and key neurotransmitters, or catecholamines, such as adrenaline, which we also call norepinephrine. We have known also for some time that these key chemicals act both as hormones and neurotransmitters. Our allopathic approach and outlook, though, has discouraged the obvious deductions that would lead to a more holistic approach in treatment.

The list of what we now call neurohormones is growing. Classically the the list includes TSH (thyroid stimulating hormone), dopamine, oxytocin, adrenaline (epinephrine and norepinephrine), vasopressin, gonatropin-releasing hormone, GRH (growth hormone-releasing hormone), CRH (corticotropin-releasing hormone), somatostatin, neurotensin, and thyrotropin-releasing hormone. Simple chemical messengers are largely described as neurotransmitters or hormones, and fall into 5 types, cholinergic, amino acid, adrenergic, peptidergic and steroidal. Neurotransmitters are classically found in all 5 categories, while hormones are typically confined to the last 3. This means that even in classical physiology that some neurotransmitters are steroidal and adrenergic, which we typically associate only with hormones. We now have proof that some hormones are cholinergic as well. While we find value in classifying some of these chemicals as neurotransmitters and some as hormones in the study of physiology, we can also find value in determining that many, of not most of these chemical messengers also act on both the neurological and endocrine systems, and trigger effects at the same cell receptors. There is no value in creating narrow boxes that use a strict binary determination, and while these definitions may make the study of physiology and anatomy simpler, they do not apply to actual medical care. Typically, we see that most neurotransmitters act over synapses and stimulate effects immediately, while most hormones travel some distance and may effect changes over longer periods of time. This is true, yet it does not negate the facts stated here that merge the systems, and it does not negate the quantum field of effects that alter the result of these messages to our cells. Because neurotransmitters are well known to act across synapses and stimulate immediate effects does not change the facts that have been discovered that they may also stimulate hormonal receptors and contribute to a broader neurohormonal effect.

Of course, ancient medical doctors such as the Daoist physicians in China, held to a strong observation of this holistic interaction between mind and body, and between the various systems in the body, recommending that most medical treatment be performed with a holistic approach. In the last decades we have learned that the neurohormone regulation of immune cytokines involves both production and function of the mileu of these immune regulating cytokines, both systemically and locally, as well as the individual's cytokine responsiveness, affecting the susceptibility to disease as well as the activity of the disease. The interplay of the hormonal and neurological systems involve much more than the hypothalamus and pituitary, but extend through the autonomic and lymphatic systems. This neurohormonal system overlays the immune genetic factors such as the MHC and HLA, and strongly interacts with the organs, or visceral systems, including the bone marrow and production and differentiation of blood cells, and the spleen pancreas with the clearing of old blood cells, lymphatic clearing, and regulation of the digestive enzymes. While we have always seen that "stress" affects disease, and a negative mood appears to accompany the worsening of a disease, modern medical doctors have long been dismissive of this obvious relationship, preferring to treat disease in a purely mechanistic manner. In 2012, experts at the Imperial College School of Medicine and the National Heart and Lung Institute in London, United Kingdom, published a paper that showed that neurohormonal and immune pathways were integral to chronic heart failure, with an imbalance of inflammatory and anti-inflammatory cytokines, chronic low-grade inflammation, and hormonal imbalances driving the disease. These experts concluded that "the immune and neurohormonal status of patients may also need to be included in the performance of a complete assessment" of heart pathology. Of course, the conclusion reached was that we may need to just prescribe more pharmaceuticals to obstruct the cytokine production, or immune suppressants, but that "these novel approaches are certainly without some risk, and many of them are expensive" (PMID: 11821625). The notion that we should perhaps integrate Complementary Medicine and TCM into the protocol, which is safe and inexpensive, is dismissed.

Is there proof that treatments in Complementary Medicine, such as acupuncture, herbal and nutrient medicines, will be effective in treating hormonal pathologies?

Yes. There is a wealth of sound research supporting acupuncture and herbal medicine in adjunct care with hormonal therapies. Links to a sample of such research is found below in Information Resources, and numerous other sound research studies and randomized controlled human clinical trials are cited and linked in other articles on the website related to hormonal pathologies, such as hypothyroidism, endometriosis, perimenopause, and diabetes, as well as research concerning brain health and neurodegenerative pathologies. There is absolutely no doubt that one of the chief measurable mechanisms of benefit in acupuncture is hormonal modulation, and both topical lipid-based bioidentical hormones from herbs and foods, phytohormonal nutrient supplements, and a few standard herbal extracts taken orally are proven to have hormonal effects.

Researchers at the University of California San Francisco have recently engaged in an official exchange of information with Peking University in China on herbal research and have published one of the first studies to result from this valuable collaboration: Selective Activation of Estrogen Receptor-beta Transcriptional Pathways by an Herbal Extract, published in Endocrinology Vol. 148, No. 2, 538-547: The authors state: "Our results demonstrate that herbal estrogen receptor beta-selective estrogens may be a safer alternative for hormone therapy than estrogens that nonselectively activate both ER subtypes." The TCM herbal formula studied was shown to accomplish the same task as Tamoxifen, a synthetic estrogen that treats both osteoporosis and breast cancer by inhibiting estrogen receptors. Tamoxifen works by selectively binding to one estrogen receptor type to effectively inhibit the effect of estradiol on the other. The chemicals in the herbal formula was found to bind to both estrogen receptors and modulate the responses, recruiting coregulatory proteins that are required for gene activation. The formula did not activate the estrogen receptor alpha-regulated proliferative genes or stimulate breast cancer cell proliferation or tumor formation in animal studies. The herbal formula would thus not induce hot flush or other side effects related to hormonal imbalance that Tamoxifen produces.

The abundance of such research prevents me from citing all of it in this article. As time goes on, I will present links to key scientific studies below. While this article is perhaps technical and difficult to fully grasp by many patients, I hope that those patients that are afflicted with hormonal pathologies take the time to try to better understand the physiology and realize how Complementary Medicine can help you to take a proactive approach and overcome these difficult health problems.

Information Resources / Additional Information

  1. A functional description of the seat of control of our hormonal, or endocrine, axis, the hypothalamic-pituitary gland in the center of the brain and the top of the brainstem, is seen here from Colorado State University: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/hypopit/anatomy.html
  2. A simple description of the adrenal glands is found on the endocrineweb.com site: http://www.endocrineweb.com/endocrinology/overview-adrenal-glands
  3. A 1998 description of the neural aspect of the adrenal glands, by the University of Minnesota School of Medicine and Department of Cell Biology and Neuroanatomy, shows that we are only fully understanding this functional aspect of the adrenals in the last decade. This study notes that even when the main nerve to the adrenals is severed, that the gland continues to secrete steroid hormones in its normal feedback balance, implying that multiple systems of feedback control exist, both neural and metabolic. This study also notes that the strong autonomic aspect of the adrenals results in both inhibitory and excitatory activity and effects in the glands, which must be encoded in the cells of the adrenals themselves, not just part of a separate neural autonomic system: http://www.ncbi.nlm.nih.gov/pubmed/9694555
  4. A 2015 study at the Yao Tokushukai General Hospital, in Yao, Japan, found that primary adrenal insufficiency was found in 5 percent of patients with autoimmune thyroid disease, although the standard literature has insisted that this is extremely rare. The problem occurs with inadequate testing and diagnostic procedures, according to these experts. These patients had normal thyroid hormone levels and were asymptomatic: http://www.ncbi.nlm.nih.gov/pubmed/26558238http://www.ncbi.nlm.nih.gov/pubmed/26558238
  5. A 2015 study at the University College London and the University of Catania School of Medicine, in Italy, showed that adrenal insufficiency was seen in over 50 percent of patients with liver cirrhosis, and appeared to relate to both adrenal dysfunction and hypothalamic-adrenal axis impairment. Such study demonstrates that adrenal insufficiency occurs outside of the diagnostic box created by standard medicine: http://www.ncbi.nlm.nih.gov/pubmed/26364559
  6. Hormonal therapy in the form of oral glucocorticoid (corticosteroid) medication is becoming more prevalent in the United States and long-term risks of this therapy have not been sufficiently studied. This 2004 study of over 50,000 patients by the Utrecht Institute in the Netherlands, the University of Montreal, Southhamptom University Medical Research Council in the UK, and the University of Edinburgh, found that very few studies have been conducted to determine the cardiovascular risk of glucocorticoid prescription, but that these medications were identified with increased risk for heart failure. In addition, these experts agreed that evidence shows increased risk for osteoporotic fractures, fluid retention, obesity, hypertension, hyperglycemia, and perhaps stroke.: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1768386/
  7. A 2006 survey of chronic glucocorticoid (corticosteroid) users by the University of Alabama concluded that there was a high prevalence of side effects or adverse health effects with normal long-term prescription use of glucocorticoid medications, including weight gain, cataracts, and osteoporotic fractures, with 55% of patients reporting at least one adverse health effect was very bothersome. Among low-dosage users, long-term use was significantly associated with acne, skin bruising, weight gain, and cataracts. All groups showed a strong association with the dosage.: http://www.ncbi.nlm.nih.gov/pubmed/16739208
  8. A 2006 survey of physician practices by the University of Texas Medical School found that physicians do not routinely evaluate patients for osteoporosis secondary to glucocorticoid (corticosteroid) treatment despite the fact that this class of drugs is the most common cause of iatrogenic (medically induced) osteoporosis. The persistent failure to recognize adverse health effects of gluocorticoids such as prednisone, as the rate of prescription of these drugs increases, has alarmed many medical experts.: http://www.jaoa.org/cgi/content/full/106/11/653
  9. A 2010 study in Czechoslovakia, at the Institute of Endocrinology in Praha, noted that standard treatment for subclinical adrenal insufficiency, or hypocorticism, in patients with diabetes type 1 remains questionable, and that risk of glucocorticoid overdose persists with standard prescription because oral administration of glucocorticoids cannot fully mimic the diurnal rhythm of natural glucocorticoid secretion, in spite of newly developed drug forms. Restoration of adrenal and hypothalamic function in subclinical adrenal insufficiency would insure greater diurnal contol of blood sugars and prevent adverse effects of glucocorticoid overdose: http://www.ncbi.nlm.nih.gov/pubmed/20429347
  10. A 2015 study at the University of Paris, in France, found that in men diagnosed with Panhypopituitarism, that an array of steroid hormones were dramatically lower than men diagnosed with Isolated Hypogonadotrophic Hypogonadism (testosterone deficiency). The hormones that were extremely low in circulation in Panhypopituitarism included pregnenelone, DHT, DHEA, testosterone, and estradiol, whereas the deficient hormones in IHH included only testosterone, DHT and estradiol. The potential for use of bioidentical pregnenelone cream for treatment of hypopituitiary disorders is evident: http://www.ncbi.nlm.nih.gov/pubmed/25393641
  11. A study at the Hollings Cancer Center of the Medical University of South Carolina found that estrogens may inhibit the T helper cell 1 (Th1) proinflammatory cytokines TNF-alpha, IL-12, and interferon gamma, but may also stimulate the production of the T helper cell 1 (Th2) anti-inflammatory cytokines IL-10, IL-14, and TGF-beta. Since chronic diseases may be moderated by Th-1 or Th-2 immune modulators, estrogen/progesterone imbalance and hormonal deficiency may play a part in these diseases. This helps to explain the high percentage of women that are afflicted with autoimmune disorders and chronic inflammatory diseases. It also points to problems with synthetic estrogen therapies, hormonal ablation, and other drug therapies that substitute or alter estrogen balance. http://www.ncbi.nlm.nih.gov/pubmed/15032646
  12. A 2015 meta-review of scientific studies of hormonal modulation of the immune system, by experts at the Temple University School of Medicine in Pennsylvania, the Albert Einstein College of Medicine in New York, U.S.A., and Tel-Aviv University in Israel, noted that an array of factors influence progestogen effects on the innate and adaptive immune systems, including use of exogenous hormones and alterations in the hormonal metabolism. They noted that progesterone has shown to have a significant effect on T cells and balance of T cell types. While standard medicine is still looking for ways to alter this immune response with synthetic progestins, they continue to ignore that this evidence indicates that a broad homeostatic field of hormonal balance is necessary for healthy immune modulation, and that altering this complex field of interacting variables with a synthetic drug is very problematic: http://www.ncbi.nlm.nih.gov/pubmed/25697984
  13. When low testosterone is found, this advice from the esteemed Cleveland Clinic, Endocrinology and Metabolic Institute, is important; namely, do not jump to the conclusion that it is a primary or secondary hypogonadism that just needs lifelong testosterone therapy. A thorough diagnostic workup is important before starting such therapy, and a low testosterone level may have many different causes. Testing of not only the initial T, FSH, LH, and prolactin, but the sex hormone binding globulin (SHBG), diurnal cortisol in saliva samples, blood protein albumin levels, DHEAS, progesterone and estradiol, distinguishing between free and bioavailable testosterone in circulation, etc. is important, as well as the attention to causes such a toxin accumulation, Klinefelter Syndrome, XX Male Syndrome, Kallmann's Syndrome (inherited propensity), autoimmune pathology, subclinical hypothyroidism, iron overload toxicity, side effects of medications, varicoceles, insulin resistance, Metabolic Syndrome, sleep apnea, liver cirrhosis, anabolic steroid abuse, acute illness, HIV, alcohol abuse, etc. This review shows that the standard treatment with testosterone replacement without a full diagnostic evaluation is just plain wrong: http://www.ccjm.org/content/79/10/717.full
  14. 2009 guidelines for diagnostic workup of testosterone deficiency, by Karolinska University and Institute, Center for Andrology and Sexual Medicine, Stockholm, Sweden is presented in this article, and shows also that the majority of men with this deficiency present not with classic endocrine disorders, but rather with metabolic syndrome, diabetes, chronic low-grade infections or inflammatory disease, COPD, or cardiovascular disease, and these consideration need to be thoroughly investigated: http://www.karger.com/ProdukteDB/Katalogteile/isbn3_8055/_86/_22/FHR37_03.pdf
  15. A 2013 study at Shahid Chamran University, in Ahvaz, Iran, found that testosterone deficiency induced by lead toxicity, as well as aldehyde toxicity in animals exposed to lead heavy metal toxicity, could be significantly restored with an alcohol extract of the herb Fumaria parviflora, analogous to the American and European Fumaria officianalis: http://www.ncbi.nlm.nih.gov/pubmed/23611729
  16. A 2011 study at S.V. University, in Tirupati, India, found that an alcohol extract of Centella asiatica, or Gotu kola, significantly reversed testicular damage and testosterone deficiency in animals with lead-induced pathology: http://www.ncbi.nlm.nih.gov/pubmed/21843793
  17. A 2011 study at Sri Venkateswara University, in Tirupati, India, also found that N-acetyl cysteine exerted significant benefit to restore testosterone production in animals exposed to arsenic toxicity, with improved testicle health and steroidogenesis, attributed to its antioxidant effects: http://www.ncbi.nlm.nih.gov/pubmed/21924885
  18. A study linking deficiency of HDL cholesterol to poor transport of testosterone and estradiol is seen here: http://humrep.oxfordjournals.org/cgi/content/full/21/9/2266
  19. Medical definitions of the various lipoproteins are available from the free dictionary online: http://medical-dictionary.thefreedictionary.com/lipoprotein
  20. A 2003 study at the Karolinska Institute, in Stockholm, Sweden, was perhaps the first published study of the ways that synthetic hormone replacement therapy and hormonal ablation therapy with Tamoxifen altered the expression of hormonal receptors, creating an imbalance of controls of receptor types that is important to maintaining cellular health and preventing cancer by controlling apoptosis, or programmed cell death. All types of synthetic hormone replacement used in menopause reduced receptor expression in the outer tissues of glands, such as the endometrium of the uterus, and created an imbalance between progesterone receptor types A and B. Tamoxifen eliminated the androgen receptors in the outer tissue of glands and the connective tissues, and increased the progesterone receptors type B expression over Type A. These findings explained the increase in specific cancers with the use of these drugs, which was stubbornly ignored by many in the field: http://www.ncbi.nlm.nih.gov/pubmed/12646074
  21. A 2002 study at the Karolinska Institute had already found that hormone replacement therapies and Tamoxifen altered the expression of estrogen type A and B in both outer tissues of endocrine glands and the connective tissues, adversely effecting the control of apoptosis, or normal programmed cell death, and explaining the increase in certain cancers due to more cell mutations allowed. This balance of receptor types on the outside and inside of cells also is important in regulation of many hormonal effects, and would explain the adverse side effects seen with these drugs: http://www.ncbi.nlm.nih.gov/pubmed/12475378
  22. A 2014 study at the Institute of Pediatric Endocrinology, in Montpelier, France, found that TCM therapy and Chinese Herbal Formula selectively modulated the homeostatic balance of estrogen receptor types, as measured by whole cell competitive binding, cell proliferation, and endogenous gene expression in estrogen receptor positive breast cancer cell lines: http://www.ncbi.nlm.nih.gov/pubmed/25300391
  23. A 2002 study at the Virginia-Maryland Regional College of Veterinary Medicine, in Blacksburg, Virginia, also proved that hormone replacement therapy exerted increased risk of cancers such as uterine endometrial cancer by increasing expression of telomerase RNA in endometrial cells, shortening telomeres and increasing risk of cell mutations: http://www.ncbi.nlm.nih.gov/pubmed/11872219
  24. A number of Chinese herbs have been found to be protective against the risks of breast cancer from use of synthetic hormone replacement. Research into the activities that make the Chinese herb, Yun Zhi, or Coriolus versicolor, commonly called turkeytail mushroom, effective against multiple breast cancer cell lines shows that this herb help induce normal apoptosis, or programmed cell death, which is inhibited with hormonal imbalance and the use of hormone replacement therapies: http://www.ncbi.nlm.nih.gov/pubmed/15908782
  25. Progress on clinical trials of Complementary Medicine in hormonal therapy continues. This 2011 study finds that a combined therapy of acupuncture and herbal formula produces a significant hormonal modulation, comparable to synthetic hormone replacement, in the treatment of postmenopausal hormonal imbalance. The use of the herbal formula alone did not produce significant effects: http://www.ncbi.nlm.nih.gov/pubmed/22314633
  26. Herbal extracts do exert hormonal effects similar to human hormones, and are often called phytoestrogens, or phytoestrogenic. While this is an oversimplification, clinical trials have demonstrated efficacy with such extracts as red clover on the autonomic symptoms related to menopause, such as climacteric vasomotor reactions (hot flush and sweats). The broad benefits of herbal isoflavones include improvements in hormonally-related pathologies as well, such as osteoporosis and cardiovascular disease: http://www.ncbi.nlm.nih.gov/pubmed/22074008
  27. A 2015 study at the National Institute for Research in Reproductive Health, in Maharashtra, India, found that the Chinese herb Cyperus rotundus (Xiang fu) exerted significant effects in stimulation of the synthesis of prolactin in laboratory animals, inducing increased lactation and milk quantity in nursing mothers, as well as improving the milk quality, with no measurable adverse effects. Such study clearly demonstrates the potential of Chinese Herbal Medicine in aiding hormonal health: http://www.ncbi.nlm.nih.gov/pubmed/25625349
  28. More and more studies find that acupuncture stimulation and electroacupuncture modulate and normalize hormonal levels, effects and receptor functions. This 2012 study at the Institute of Neuroscience and Physiology, University of Glasgow, shows that hormonal levels may be normalized in polycystic ovary syndrome to improve menstrual frequency: http://www.ncbi.nlm.nih.gov/pubmed/22337865
  29. A 2012 study at Gazi University Medical School, in Ankara, Turkey, found that standard acupuncture treatment for premenstrual syndrome (PMS) was a very effective treatment protocol, with both symptom relief and improvement in biochemical markers, such as inducible nitric oxide and better glutathione levels: http://www.ncbi.nlm.nih.gov/pubmed/22905466
  30. A 2011 study in Russia found that acupuncture aided normalization of thyroid hormone levels and decreased symptoms in patients with subclinical hypothyroidism: http://www.ncbi.nlm.nih.gov/pubmed/22165143
  31. A 2011 study at the Chinese Academy of Chinese Medical Sciences, in Beijing, China, found that acupuncture stimulation at the single point ST36 on laboratory animals with induced testosterone deficiency resulted in significant increase in testosterone and estradiol (E2): http://www.ncbi.nlm.nih.gov/pubmed/21942180
  32. A review of the pioneering work of Jonas Salk: http://www.jonas-salk.org/docs/Legacy.html
  33. A 1987 study in Russia showed that in 106 patient diagnosed with the autoimmune disorder thrombocytic purpura, that decreases in the active thyroid hormone T3 correlated with refractory T-cell responses when there occurred exacerbations of the disease, and this was accompanied by increased cortisol and IgM antibody levels. Treatment for this condition with glucocorticoids (corticosteroid or Prednisone) produced a decrease in both the thyroid hormone T3 and the refractory T-cell levels. This study showed that changes in the hormonal levels were accompanied by corresponding levels in the immune cells: http://www.ncbi.nlm.nih.gov/pubmed/3502295
  34. A 2012 article by experts at the Imperial College School of Medicine and the National Heart and Lung Institute, in London, United Kingdom, found that immune and neurohormonal pathways were integral to chronic heart failure, and should be included in the diagnostic assessment of the disease. What these experts are loathe to suggest is that a more holistic and integrative approach to treatment is needed, instead suggesting that more pharmaceuticals should just be added to the treatment, with immune suppressant drugs, even though they acknowledge that this would involve considerable risk of adverse health effects, and considerable cost: http://www.ncbi.nlm.nih.gov/pubmed/11821625
  35. A 2008 paper by the Institute of Neurobiology and Molecular Medicine of the Italian National Research Council outlines the many ways that the neurohormonal system affects the immune system, in effect producing an overlay of the hormonal balance and the balance of immune responses, particularly the Th1/Th2 balance in autoimmune diseases, the effects of hormonal imbalance in obesity on chronic inflammatory diseases, and the effects of mood disorders of anxiety and depression on disease progression and pathogenesis: http://www.uccs.edu/Documents/rmelamed/elenkov_2008_17716784.pdf
  36. Medical textbooks, such as this one in 2001, have made clear that many peptide (protein-based) neurotransmitters act as hormones as well, but like this text, standard authors have been loathe to actually list these neurohormones and explain the many ways that they act as both neurotransmitters and hormones, or the fact that many receptors on cells work by stimulation from contact with either the neurotransmitters or hormones: http://www.ncbi.nlm.nih.gov/books/NBK10873/
  37. As far back as 1985 we see research that notes that TSH, or thyroid stimulating hormone peptide, has broad effects on the nervous system, the immune system, and here researchers found that TSH levels in the neural part of the hypothalamus-pituitary gland, the hypothalamus, balance with the levels of TSH in the pituitary, or endocrine part of the complex. This research also noted that removal of the adrenal glands resulted in an expected drop in pituitary TSH, but also a like increase in the hypothalamic TSH levels, and that with the removal of the adrenergic feedback the levels of TSH in the brain remained the same, indicating that TSH has a significant CNS role, and that the adrenal axis is not the only determinant of TSH expression: http://www.ncbi.nlm.nih.gov/pubmed/4075171
  38. A 2008 study at the University delgi Studi di Palermo, in Palermo, Italy, noted an array of effects of thyroid hormones and TSH on the nervous system, many of which occur outside of the typical hormone receptors, which typically affect gene expression. Thyroid hormone effects were noted in many tissues that were mediated by integrins and acted on calcium-dependent neuroreceptors, both in the cells and in the mitochondria. In addition, this study notes that even on typical nuclear hormone receptors, that the hormone may trigger either activation or repression of the gene expression, showing that the quantum field of neurotransmitters and hormones is important in the actual effects of the hormones, not just the presence of the hormone by itself: http://www.ncbi.nlm.nih.gov/pubmed/21479409
  39. A 2010 overview of our understanding of thyroid hormones, by experts at Colorado State University, in the U.S.A., notes that thyroid hormones appear to target all cells in the body, including the neurons, and that the nervous system is directly affected by increases or decrease in the thyroid hormone concentration. Other studies have noted changing levels of various nerve receptor types in varied areas of the body, in response to changing levels of TSH and thyroid hormone concentrations. For example, thyroid variances were found to be associated with expressions of muscarinic receptors that reacted differently in the brain and heart. Some studies have noted seasonal variation in the expression of these neuroreceptors as well. All of this study continues to confirm that the system must be looked at both in relation to specific and separated effects, and holistically, if we are to devise the best medical protocols: http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/physio.html