Introduction

Understanding the Hormone circuit of the NeuroEndoMetabolic (NEM) Stress Response model is essential to an understanding of the entire model. It lays the foundation for the two components, divided into six circuits, involved in how the body responds to stress.

Signals from the brain control the Hormone circuit which is regulated by the adrenal glands, the reproductive system, and the thyroid. Even though this process has been repeatedly studied, it is important to understand its workings.

Key pathways for the Hormone circuit to perform its duties lie in the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis.

An illustration of The Hormone Circuit The adrenal glands are small glands located on top of the kidneys. These small glands do a lot of work for the body. One of their major functions is to release cortisol into the bloodstream in addition to over fifty other hormones.

With the number of hormones involved in this circuit, it is easy to see how these three components are interconnected.

For example, when adrenal function is low, thyroid function is also low. The thyroid gland regulates the temperature of the body and the total stress response speed, among many other functions. When thyroid function is low, fatigue results.

When the body is slowed down due to fatigue, reproductive processes become of secondary concern and libido is reduced. The ovarian-adrenal-thyroid (OAT) axis is the governing pathway to assure sufficient hormones are available for reproduction. Disruption of this pathway will lead to disruption in the other systems.

What happens to one of these organ systems affects the other organ systems in this circuit. They depend on each other hormonally to bring about optimal functioning. Their effect on each other can occur physiologically, clinically, or sub-clinically.

For optimum functioning, the three organ systems must be in balance. Unfortunately, this balance is not always achieved.

For example, if the adrenal glands become weak or fatigued, there is often concurrent malfunction of the thyroid gland and irregularity of the menstrual cycle. If the thyroid is less active, it tends to exacerbate adrenal fatigue. In addition, with ovarian hormone imbalance, such as estrogen dominance, any pre-existing hypothyroidism may be exacerbated.

If the Hormone circuit becomes dysfunctional, there are a number of symptoms that become evident. Among them are:

  • Hair loss
  • Fatigue
  • Infertility
  • Exercise intolerance
  • PMS
  • Feeling cold when others are warm
  • Irregular menses
  • Low libido

These symptoms typically start off mild and increase in severity as dysfunction continues.

As stress continues and the NEM response increases, thyroid function typically slows more. This is the body’s attempt at conserving energy by slowing the basal metabolism rate through decreased thyroid function.

When the OAT axis becomes imbalanced, one component organ tends to become more problematic and thus clinically dominant. Imbalances in the OAT axis typically are not equal among the adrenals, gonads, and thyroid. The part that is clinically dominant is typically the most damaged and constitutionally weakest.

Those who are thyroid dominant typically present with severe low energy in addition to the more frequently encountered signs of low thyroid functioning such as dry skin and inability to lose weight. Clinically, they complain most of fatigue, being too tired to care about PMS or even about being depressed.

Those who are adrenal dominant usually present with complaints of fragile emotions such as irritability and anxiety. Physically, they are tired but are consumed with the ups and downs of their emotional state that comes with their easily triggered rage or anger.

The ovarian dominant people most of the time will present with memory loss and brain fog. These symptoms come in addition to PMS and other estrogen dominance symptoms.

The hormone circuit of the NEM stress response model is the foundation for how the body responds to stress. Governed by the brain, the HPA and HPG axes regulate the functions of the three components of the hormone circuit: the adrenals, gonads, and thyroid. These three organs are interconnected through the hormones each secretes and as each responds to the hormones of the others.

Components of the Hormone Circuit

As was discussed in the introduction, the three components of the Hormone circuit must work in balance in order for the body to perform at its peak. These three components – the adrenal glands, the thyroid gland, and the reproductive system – will now be discussed in detail with particular emphasis on their roles and reactions when stress affects the body.

Adrenal Glands

The adrenals sit atop the kidneys and, while small, play a major role in how the body responds to stress. They are triggered by the release of hormones from the hypothalamus when stress becomes problematic.

In today’s culture, stress is inevitable. Work, family, finances, and environment are only some of the sources of stress. Add into this mix the potential stressor of health issues and the extent of stress becomes apparent.

Thankfully, the body has an automatic mechanism for dealing with stress regardless of its source. The first step in handling stress comes when the hypothalamus releases corticotropin-releasing hormone (CRH). This hormone stimulates the pituitary to release adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenals to release their stress-fighting hormones. Once this has been accomplished, cortisol sends signals back to the hypothalamus and pituitary to stop releasing their hormones.

The two major stress-fighting hormones initially released by the adrenals are cortisol and aldosterone. Cortisol has important regulatory functions to perform in the body in addition to its stress-fighting functions. This makes it important for cortisol to be in balance.

If the levels of cortisol are too high, there are health issues that can result. Some of these are:

  • High levels of glucose
  • Obesity
  • Weak muscles
  • Diabetes
  • High blood pressure
  • Low potassium levels
  • High bicarbonate levels
  • Increase in body hair

If cortisol levels are too low, some of the following health issues may arise:

  • Low levels of glucose
  • Low levels of sodium
  • High calcium levels
  • Fatigue
  • Low blood pressure
  • Decreased appetite
  • Weight loss
  • Weak muscles

Aldosterone is the adrenal hormone that plays a major role in regulating blood pressure. It does this by regulating sodium-potassium levels in the body, affecting water retention. When water is retained in the body, blood pressure increases. When too little water is retained, blood pressure decreases.

When aldosterone is low, the body loses sodium and retains potassium. Low sodium levels mean low blood volume and low blood pressure. It can also lead to hyponatremia with some of the following symptoms:

  • Muscle seizures
  • Muscle twitches
  • Confusion
  • Fatigue

Hyperkalemia is a condition resulting from high levels of potassium. This condition may not have particular symptoms, but the following may result:

  • Irregular heartbeat
  • Nausea
  • Pulse that is slow, irregular, or weak

When the adrenals are stimulated due to the presence of stress, they release high levels of cortisol initially to deal with the effects of stress. If the stress is temporary and can be dealt with by this initial level of cortisol, the adrenals stop releasing large amounts once the stressor is gone.

However, in the stress-filled culture of today, stress typically becomes continuous, severe, and chronic. In this case, the adrenals are continually called upon to release more and more cortisol in an attempt to handle the stress effects.
With chronic stress, the adrenals get to the point of not being able to continue releasing sufficient amounts of cortisol. Eventually, they become so fatigued that they are unable to continue to function adequately. It is here that Adrenal Fatigue Syndrome (AFS) may begin.

Sitting atop the kidneys are the adrenal glands. They are stimulated to release the major stress-fighting hormone cortisol when triggered by chemical signals from the pituitary gland. Both cortisol and aldosterone are released when the adrenals respond to these signals. If the stress becomes chronic, the adrenals may reach a point of not being able to release a sufficient amount of cortisol and adrenal fatigue may set in.

Reproductive System

The human reproductive system is made up of the ovaries (female) and testes (male). Both parts of the system require hormones to work properly and exhibit symptoms when the hormones are out of balance. This imbalance appears to be more obvious in females.

The reproductive system and The Hormone CircuitIn females, two hormones, estrogen and progesterone, are most clearly involved in the day-to-day functioning of the system. When these two hormones are in balance, the female reproductive system works well.

With estrogen and progesterone in balance, the female’s typical 28-day menstrual cycle continues working as it should. Estrogen levels rise beginning on day one of the cycle, typically peaking around day fourteen. If there is no fertilization at this time, estrogen levels begin dropping until the onset of menses at day twenty-eight. At the same time, progesterone levels begin rising about day fourteen and continue rising until day twenty-eight. If there is no fertilization, the progesterone is not needed to support the fetus, and its levels begin declining as menses begins.
It is important to understand that a fine balance between estrogen and progesterone is needed during the menstrual cycle in order for reproductive functioning to be optimal. If the balance gets upset, problems with reproduction result. This is true not only for absolute levels of either hormone, but if the balance is off relative to each other.

Normally, over time the levels of both hormones decline. But while this decline is seen in both hormones, the amount of progesterone lost is greater than that of estrogen. This leads to the kind of imbalance discussed above and results in problems. Estrogen dominance may begin when the relative amounts of estrogen and progesterone are imbalanced in favor of estrogen, even if the absolute levels of both may be in the normal range.

Another aspect of the balance between these two hormones can be seen in the normal effects they have on the human body. Estrogen is described as a pro-growth hormone. Its normal effects include:

  • Breast stimulation leading to menarche
  • Stimulating the endometrium to proliferate
  • Increase in endometrial cancer risk
  • Increase in body fat
  • Restraining of osteoclasts

Progesterone balances estrogen by completing functions opposite to estrogen. Some of these functions include:

  • Protecting against fibrocystic breast disease
  • Helping to use fat for energy
  • Protecting against breast cancer
  • Maintaining secretory endometrium
  • Helping prevent endometrial cancer

There are multiple ways for estrogen to increase in the body. In addition to environmental estrogens that will be discussed later, two other body systems affect the production of estrogen: the adrenal glands and adipose tissue.
Estrogen levels increase in the body when the adrenals are under stress. People who are overweight have more adipose tissue. Estrogen is produced by this adipose tissue. Also, dietary factors influence the production of estrogen.

The adrenal glands are responsible for synthesizing many of the hormones in the body, including the ones most involved in the reproductive system. They use cholesterol as a building block for producing a prohormone, pregnenolone, which is the mother of all other hormones. Pregnenolone can be converted into progesterone which is then converted into cortisol.

In addition, pregnenolone can be converted into DHEA and other male hormones as well as into estrogen. If the adrenal glands are working as they should, the progesterone level in the body will be in balance with the three types of estrogen. Those types are estrone, estradiol, and estriol.

Remember, when under stress the adrenals are called upon to produce more and more cortisol to fight the effects of stress. As this occurs, more and more pregnenolone is utilized in the making of cortisol. This process is called ‘pregnenolone steal’. More cholesterol is used in making pregnenolone which is then converted into progesterone to be ultimately converted into cortisol as the stressed body demands it. In this process, both pregnenolone and progesterone can become depleted. This depletion leads to a shortage of progesterone to balance estrogen. The ultimate result then becomes estrogen dominance.

This means that anything that stresses the body and adrenal glands will have the potential to deplete progesterone and increase estrogen. People with Adrenal Fatigue Syndrome tend to be estrogen dominant because of this, with some symptoms such as endometriosis, irregular menses, PMS, fibroids, and fibrocystic breast disease.

As AFS continues, the symptoms grow in severity. Once the adrenals reach a near-failure state, another mechanism is triggered that shuts the body down to conserve energy, resulting in amenorrhea. This is the same process that occurs when relatively young women are training for any extreme sport such as a marathon. Their menstrual cycle shuts down as the body seeks to conserve energy during a time it perceives as stressful.

What can be seen clearly is that the hormonal systems and the reproductive system are not independent. They are connected through networks such as the Ovarian-Adrenal-Thyroid (OAT) axis. When something happens in the adrenal system, the ovarian/reproductive system is affected also. Whatever happens to the ovarian system also affects the thyroid. This is why it is important for all these three systems to be in balance.

The reproductive system consists of the ovaries in females and the testes in males. They are affected by a number of hormones that also play a part in the body’s response to stress. When stress becomes chronic, the body attempts to conserve energy which means those bodily processes such as reproduction that are not necessary for the body’s survival are shut down.

Thyroid Gland

The thyroid gland is a small gland lying in the front part of the neck below the Adam’s apple. Although small, the thyroid performs many important functions through its hormones. The functions of the brain, heart, and muscles rely on these hormones. Also, they affect metabolism, energy use, and the feeling of warmth in the body.

There are two ways in which the thyroid can malfunction. One is hypothyroidism in which the thyroid is under-functioning. This condition can lead to dry skin, thinning hair, fatigue, and constipation. Hypothyroidism affects women more frequently than men and is a relatively common condition.

The other way the thyroid can malfunction is hyperthyroidism. This is a condition in which the thyroid is overactive. Some results include sensitivity to heat, hair loss, irritability, hyperactivity, trembling, and anxiety.

The thyroid hormones and the hormone circuitThe importance of the thyroid hormones can be highlighted by the fact that they are distributed throughout the body in the bloodstream. Virtually every cell in the body is dependent on these hormones for appropriate metabolism. Production of the thyroid hormones begins with thyrocytes producing triiodothyronine (T3) and thyroxine (T4). These two hormones are formed by combining iodine from food with tyrosine, which is an amino acid used in the synthesis of proteins. Thyroid cells are the only body cells that can absorb iodine. Two other hormones, T1 and T2, are also produced in small amounts. Their functions are not fully understood at this time.

T4 is called a prohormone and is converted into T3, the active thyroid hormone. The body only contains receptors for T3. About four times as much T4 is produced as T3, but T3 is about four times more powerful than T4.

Stimulation of the thyroid to produce these hormones is carried out by the hypothalamus and the pituitary gland. This stimulation is necessary for the thyroid to produce and release its hormones. Also, the thyroid has to be stimulated to stop production when sufficient levels have been reached.

The first step in this process is the hypothalamus releasing thyrotropin-releasing hormone (TRH). This TRH then stimulates the pituitary to release thyroid-stimulating hormone (TSH). TSH then signals the thyroid to begin the process of producing T3 and T4.

Optimal levels of T3 and T4 are key to the proper functioning of the body. An imbalance either way can eventually lead to hypothyroidism or hyperthyroidism.

TSH is the key to maintaining this balance. If the hormones become too high, the pituitary slows the release of TSH. This leads to decreased production of T3 and T4 by the thyroid. If the levels of these hormones get too low, the pituitary releases more TSH to stimulate increased production of the thyroid hormones.

The optimum levels of these two thyroid hormones can become upset for any of several reasons. Some possible reasons for this imbalance include:

  • Failure to convert T4 to T3
  • Primary hypothyroidism or failure of the thyroid. This is the most common reason for an imbalance of the thyroid hormones.
  • Secondary hypothyroidism – low TSH due to failure of the pituitary
  • Tertiary hypothyroidism – low TSH due to failure of the hypothalamus
  • Type 2 hypothyroidism or thyroid resistance. This is due to receptor uptake failure and is the same nomenclature as Type 2 diabetes to differentiate it from Type 1
  • Adrenal insufficiency that comes with lowered levels of cortisol that affects the thyroid functions of production, conversion, and receptor uptake

Alleviating a thyroid imbalance is a difficult task, possibly one of the most difficult to manage of all endocrine disorders. The underlying root cause as it is affected by the adrenal and ovarian systems often prevents a successful resolution.

The intricate relationship of the thyroid with the adrenal and ovarian systems is shown clearly in its role in regulating metabolism. In this process, the thyroid affects the activities of the reproductive glands.

Its effects on the menstrual cycle and the ability to get pregnant come through its influence on the production of sex hormone binding globulin (SHBG), gonadotropin-releasing hormone (GnRH), and prolactin. Progesterone production in the ovaries is also influenced by the thyroid. Progesterone is important for pregnancy because it provides a supportive environment in the uterus for the egg. Too little progesterone will result in no pregnancy.

These kinds of issues with the menstrual cycle do not only apply to young women. When women experience infertility or PCOS, lack of progesterone is usually present. Thyroid problems that go without remediation in premenstrual women can lead to increased problems. Infertility, PMS, and menopausal issues are some that can be attributed to thyroid problems.

Also, the hormones produced by the thyroid and some metabolites of estrogen and progesterone share some similarities. Estrogen and progesterone can also inhibit or facilitate receptor sites for thyroid uptake.

Imbalances of estrogen and progesterone along with imbalances of T3 and T4 can mimic menopause symptoms. Adverse effects on energy, sleep, mood, fluid retention, and temperature regulation can result.

Just as there is a close connection between the thyroid and the ovarian system, this same kind of close relationship exists between the thyroid and the adrenals. Under conditions of chronic stress, the adrenals become fatigued and ultimately the body begins shutting down some processes in order to conserve energy. This conservation of energy demands less work and more rest for the body. The body is metabolically slowed at this point. Since one of the functions of the thyroid is regulating metabolism, there is a significant effect on the thyroid.

As this slowdown occurs, the production of T3 and T4 is reduced. At the same time, there is an increase in thyroid-binding globulin (TBG). This results in more of the thyroid hormones being bound and thus unavailable for the cells. Another result is lowered free T4 and T3 in the body even though tests may show normal levels of total T4 and T3.
Cortisol levels are typically high when the body is under stress. Cortisol is able to inhibit the conversion of T4 into T3 and may also inhibit the hormones’ entry into cells.

At the same time, the body may change the conversion of T4 into T3 by making it convert into rT3 (reverse T3). rT3 serves a braking function opposing the function of T3. This leads to a decrease in T3 and an increase in rT3 that may persist even after the stress has been resolved and the system returns to a normal state.

In addition, rT3 can inhibit the conversion of T4 into T3. This condition can result in increased rT3 that can then lead to a condition called rT3 dominance. This rT3 dominance may lead to symptoms of hypothyroidism in spite of normal levels of circulating T4 and T3.

Other potential causes of a decrease in the conversion of T4 into T3 include:

  • Dieting
  • High stress levels
  • Low levels of zinc, selenium, and iodine
  • Some medications such as Dilantin and beta blockers

This is one example of the many pathways the body can use to slow down energy production in an effort to preserve its existence and increase the likelihood of survival.

At this point, the use of medication to remediate what appears to be hypothyroidism is going to exacerbate the problem. The types of medications used in this case are designed to speed up the metabolism at a time when the body is striving to slow down. The two goals are diametrically opposed to each other.

For a short while, the administration of these medications may lead to a reduction in symptoms and an increase in energy. This will be temporary. Before long, the fatigue experienced before will return as this medication serves to exacerbate the underlying adrenal problems and may precipitate an adrenal crisis. The fatigue will increase in severity beyond the limits of the medication’s ability to combat it.

Conventional medicine and the hormone circuitConventionally trained medical professionals will see the need for increased dosages of the medications or for more powerful medications to continue the initial improved lab results. Without taking into consideration the amount of free T3, free T4, and rT3 the amount of the medication actually getting into the body’s cells remains unknown.

Continuing to increase the amount of medication will simply lead to the adrenals being subjected to its negative effects more and more. In this situation, the adrenals will continue attempting to slow down the body’s metabolism in an effort to conserve energy, thus blunting the body’s response to the thyroid medication.

This leads to an ever-increasing need for more medication to maintain the small amount of improvement. Unfortunately, a person being “helped” by these means remains symptomatic. Stronger and stronger medications are tried in a trial and error manner, seeking one that will alleviate the symptoms completely. With these stronger medications, the body continues to deteriorate.

The ultimate result is a body that is saturated with thyroid medication with adverse side effects such as heart palpitations and tremors appearing. The person continues to feel fatigued at the same time. This is the “wired and tired” sensation often experienced by people who have adrenal fatigue.

The third of the components of the hormone circuit, the thyroid gland, is intimately connected to both the adrenals and the reproductive system. Its connection to the reproductive system is seen in the multitude of effects the thyroid hormones have on the reproductive system. The relationship of thyroid to adrenals is apparent in the effects of cortisol on the thyroid hormones. Also, the slow-down of the body as the adrenals become fatigued affects the metabolism regulating function of the thyroid hormones. Thyroid regulating medications can also affect the functioning of the adrenals.

Hashimoto’s Thyroiditis

It is important to note that the dysfunctions of the thyroid discussed above are sometimes assessed inaccurately as Hashimoto’s Thyroiditis. Hashimoto’s is an autoimmune condition in which an overactive immune system targets the thyroid and attacks it as an invader of the body. As the thyroid undergoes this attack, inflammation sets in and the thyroid deteriorates. Ultimately, it becomes unable to produce the hormones that are so vital for the body’s optimum level of functioning.

Hashimoto’s is the most frequently seen cause of hypothyroidism, affecting about 10 million people in the U.S. It occurs much more often in women than men, 10 to 20 times more often. Most of the time, this condition first occurs between the ages of 30 and 50, although it has been seen in children, as well.

Normally, the immune system functions as the guardian of the body against pathogens and foreign substances that can cause the body harm. Under some circumstances, chronic stress being one of those circumstances, the immune system can become hyperactive. In this state, the immune system sends out multitudes of cells designed to attack and neutralize these pathogens. In this state, the cells may also begin attacking the body’s own cells in a case of mistaken identity. They perceive the normal cells as pathogens.

In this attack, inflammation plays a major role. Whatever cells are attacked, the thyroid in the case of Hashimoto’s, are enveloped in inflammation.

When the body is in a state of overactive immune reaction, the clinical picture can become confusing. Typical symptoms of an autoimmune condition such as joint pain and fatigue can be experienced. When under chronic stress, the body typically already has an existing microbiome imbalance, reactive metabolite overload, or a GI tract irritation. Any of these conditions can make distinguishing between a genuine autoimmune condition, such as Hashimoto’s, and symptoms that only suggest an autoimmune condition very difficult.

In the case of symptoms that suggest autoimmune conditions, lab results may add to the difficulty. They may be borderline high or even normal and not the very high values that would be seen in a genuine autoimmune condition.
When these lab results that are normal or borderline high are found with symptoms such as joint pain, psoriasis, fatigue, weight gain, muscle ache, vasculitis, and gastric discomfort, most health professionals will decide on the patient has an autoimmune disorder. They are not trained to evaluate the body holistically to determine whether there may be a hyperactive immune system or AFS present.

The typical medical response in this case is to administer steroids or autoimmune medications. Over the short term, this may bring some benefit as the steroids relieve the inflammation. Unfortunately, the long term use of steroids has some very negative side effects. One of these is to suppress immune function, thus masking the root cause of symptoms. Much of the time there are excessive metabolites if a hyperactive immune system is the problem. In the slow deterioration of the body that results, the thyroid gland is greatly at risk.

Potential Causes of Hashimoto’s Thyroiditis

Goiters and the hormone circuitAlthough the exact causes of Hashimoto’s are not known, there does appear to be a genetic component. The condition runs in families. Thyroid-specific genes such as the TPO genes and the thyroglobulin genes appear to be involved. Even with a genetic predisposition to the condition, a person may not develop the condition. Environmental triggers are needed in order to stimulate the genes involved into developing Hashimoto’s.

The specific environmental events that serve as triggers for these genes are still being debated. Stress does appear to be a significant triggering event. Having other autoimmune conditions increases the risk of developing Hashimoto’s, as is the presence of papillary thyroid cancer.

Also called chronic lymphatic thyroiditis, Hashimoto’s thyroiditis causes a hyperactive immune system to release lymphatic white blood cells to the thyroid. These white blood cells destroy cells that produce T3 and T4. Given sufficient time, this can cause a swelling of the thyroid gland, called a goiter.

In the beginning stages, the symptoms of Hashimoto’s are practically unobservable. The condition is also very slow to progress. It is similar to AFS in this way, with the initial symptoms often being overlooked by medical professionals. They typically are not dealt with until the condition is advanced.

Hashimoto’s Thyroiditis is an autoimmune condition in which a hyperactive immune system begins attacking the thyroid in a case of mistaken identity. Lymphatic white blood cells are dispatched to the thyroid and begin to destroy the cells that produce T3 and T4. The resulting swelling of the thyroid can become noticeable and is called a goiter. Typically, the initial symptoms of this condition are overlooked until the damage to the thyroid has become unmistakable.

Effects of Stress on The Adrenals

Now that you have a basic understanding of how the three elements of the Hormone circuit function and how they can become dysfunctional, it is clear that they can all be affected by stress and adrenal dysfunction. Understanding the progression of this dysfunction is, therefore, essential.

The adrenal glands carry out the main stress control functions of the body. Their production and release of cortisol is the first line of defense against the effects of stress. As stress becomes severe and chronic, the adrenals become less and less able to carry out their functions. This is when adrenal fatigue begins.

Chronic, severe stress can come from any source: physical, emotional, mental, or environmental. When this stress becomes too great for the adrenals to control, adrenal fatigue.

Signs and symptoms of adrenal fatigue are many and sometimes vague. This vagueness is the reason so many healthcare professionals miss the assessment of the condition. Some symptoms include:

  • Central weight gain with the inability to lose it
  • Increasing susceptibility to infections with increased severity
  • Chronic pain of unknown origin
  • Lightheadedness when rising from prone position
  • Trembling under pressure
  • Brain fog
  • Decreased sex drive
  • Increased fatigue in the afternoon
  • Fibromyalgia
  • Reliance on coffee to get the day started
  • Chronic fatigue
  • Hypoglycemia
  • Feeling better on vacation
  • Cravings for salty and fatty foods

While none of these signs or symptoms in themselves point to adrenal fatigue, taken together in an otherwise healthy person they suggest the presence of Adrenal Fatigue Syndrome. The picture is that of a healthy person under stress and the body’s clear failure to deal with such a burden. AFS is not recognized as a clinical condition by conventional medicine and is missed by most conventionally trained medical personnel.

The adrenal glands are impacted significantly by stress. Normally, their production and secretion of cortisol and other stress hormones is sufficient to combat the effects of stress. However, with chronic stress, the adrenals may become overwhelmed and unable to produce sufficient levels of hormones. This is the onset of AFS.

Stages of AFS

When AFS becomes a problem, it progresses through several stages of severity. Each stage shows a unique set of symptoms and signs ranging from mild to moderate to severe as the condition progresses.

Stage One: Alarm Response

This is the stage in which the body begins recognizing the threat of stress and starts the natural response to deal with it. The adrenals are stimulated to produce and release increasing levels of cortisol to fight against the effects of stress. In this stage, the demand on the adrenals for these levels of cortisol is within their ability to meet. Life typically goes on normally overall, with the possibility that the person begins seeing a need for a stimulant such as coffee to get the day started. Toward the end of this stage more and more coffee is needed at the beginning of the day. In general, what symptoms may be present are very mild, and no decompensation is noted.

Stage one of AFS is regarded as the alarm stage in which the body deals with the effects of stress by means of increased cortisol production by the adrenals. If any symptoms are present, they are very mild.

Stage Two: Resistance

The hormone circuit and stage two AFSIn this stage, stress becomes more severe and chronic. The adrenals become less and less able to keep up with the demands placed on them for increasing levels of cortisol to fight the stress effects. Most of the time, daily functions are carried out normally, but a person begins feeling significant fatigue at the end of the day and requires more rest than usual. However, even after resting for a full night, a person continues to feel fatigued the next morning. Anxiety and irritability become more pronounced. Both sleep onset sleeplessness and sleep maintenance sleeplessness occur more and more often. Infections occur more often, as well. Symptoms of hormone imbalance such as PMS and menstrual irregularities can be seen frequently. Symptoms that suggest hypothyroidism, such as feeling cold and having a sluggish metabolism, become more prevalent.

Stage two of AFS is when the stress level increases and becomes chronic, and the adrenals can’t keep up with the demand placed on them. Fatigue is more frequent, and rest doesn’t seem to help. Symptoms such as anxiety, PMS, and sleeplessness become common.

Stage Three: Exhaustion

One of the major symptoms of this stage may take years to be fully known. This is when adrenal production of cortisol becomes extremely low. The adrenals are no longer capable of meeting the continuing and increasing demand for cortisol. Output of the stress-fighting hormone will plateau and even begin to decline.

The potential symptoms resulting from this stage of AFS can be numerous, confusing, and overwhelming. To help with understanding this clinical picture, this stage is divided into four broad phases. Each of these phases, and the symptoms within them, are overlapping as well. The phases are not meant to be distinct or an absolute process through which people with AFS progress. Most people with AFS will present with symptoms from different phases at the same time.

Phase A: Chronic Single System Dysfunction. The main concern in this phase is the symptoms that showed up in the first and second stages become chronic and worsen. Some of those worsened symptoms are the following:

  • Slightly high blood pressure now becomes chronically low.
  • Recurring infections become frequent as opposed to intermittent.
  • Fatigue that came after a stressful day now comes every day.
  • PMS happens monthly.
  • Previously mild musculoskeletal pain now grows into fibromyalgia daily.
  • Hormone imbalance symptoms worsen.
  • Occasional blue feelings become mild depression.
  • Sleeplessness becomes more significant.

More difficulty is felt in continuing normal daily activities. Different organ systems become dysfunctional at different times, with the constitutionally weakest breaking down first. People who suffer from AFS begin seeing sometimes multiple healthcare professionals with little or no relief. Instead, their symptoms may actually become worse.

Phase B: Multiple Endocrine Axis Dysfunction. Increasingly, the axes that regulate hormonal systems become more dysregulated themselves, creating a negative feedback loop that leads to a cascade of decompensating multiple organ systems. The Ovarian-Adrenal-Thyroid (OAT) axis in women and the Adrenal-Thyroid (AT) axis in men are two of the more important ones. Typically, for women, symptoms include imbalanced ovarian hormones, low thyroid function, and decreased adrenal function. For men, both the adrenals and thyroid show signs of dysfunction. There is significant confusion during this phase and a deterioration of the physical and emotional states. People who suffer from this phase of stage three of AFS are not able to deal with the multiple physical signs and symptoms that occur due to multiple imbalances of the hormonal axis. Conventionally trained healthcare professionals likewise don’t grasp the confused and myriad symptoms. In some cases, people with this condition are even abandoned by their healthcare professionals. This leaves the sufferers with little recourse except to try many approaches in a trial and error fashion. Often, this leads to a worsening of symptoms.

Phase C: Disequilibrium. With continued deterioration, the downward momentum gathers strength. Hormone imbalance symptoms become more unmanageable. In its efforts to gain homeostasis again, the body gradually becomes severely compromised. Normal equilibrium is lost. As the body struggles to regain this equilibrium through responses in the autonomic nervous system that are designed to compensate for lost functions, paradoxical and exaggerated responses emerge due to damaged receptor sites and impaired metabolic and detoxification pathways. Some of the common hormone imbalance symptoms during this phase include:

  • Strong heartbeat
  • Temperature intolerance
  • Dizziness
  • Heart palpitations
  • Anxiety
  • Adrenaline rushes
  • Orthostatic hypotension

These responses serve to further weaken adrenal function. This continued weakening is seen in:

  • Night sweats
  • Fragile blood pressure
  • Swings in blood sugar levels
  • Hyper-anxiety followed by depression
  • Reactive hyper-adrenergic responses including heart palpitations

In a very real sense, the body is falling apart during this phase. Because of the severity of symptoms, people in this phase of stage three of AFS must be under the care of a rigorously trained medical professional.

The hormone circuit and later stages of AFSPhase D: Near Failure. It is important to keep in mind during this phase that all hormones are to an extent dependent on others to function appropriately. And the body is aware of this. In the case of cortisol, once the level available falls below what is necessary for daily functioning, the body may reduce the amount needed so that it can preserve the amount left for necessary functioning. Down-regulation of this sort further reduces the output of cortisol, increasing the downward cascade of symptoms. Paradoxical reactions become extreme and may get worse due to the buildup of toxic metabolites in the body.

This down-regulation of one organ system leads other organ systems to also down-regulate because of the inter-relatedness of the systems. Some of the results of this multiple organ down-regulation include:

  • Metabolite clearance slows in an effort to conserve energy.
  • Weight loss becomes very difficult.
  • Digestion slows to conserve energy.
  • The basal metabolic rate decreases to conserve energy.
  • The adrenals lose most of their stress control ability.
  • The body becomes hypersensitive and reacts negatively to attempts to remediate it.
  • Frequent adrenal crashes defy logical explanation.
  • Nutrients that are basic to adrenal function such as vitamin C are severely depleted.
  • Administering vitamin C, cortisol, DHEA, or pregnenolone, usually well received and used by the adrenals, may become toxic or at least ineffective.
  • As the adrenals become more exhausted, the less they tolerate medications or supplements.

At this point, the severe downward progression has become solidly established. Nothing seems to help. The administration of any medications or supplements may actually worsen the condition. Due to desperation and no relief from remediation attempts, depression sets in and suicidal tendencies increase.

Stage three of AFS is divided into four phases to help clarify the symptom picture. A worsening of the symptoms seen in stages one and two begin the downward spiral of decompensation and dysfunction seen in this state. Progression through the phases is not the intent, rather, people can experience symptoms of some or all of the phases at the same time. Increasing severity of symptoms is seen in each phase.

Stage Four: Failure

In this stage, the adrenals have become completely exhausted. There is a high potential for people in this stage to develop cardiovascular collapse and die. The line between this stage of AFS and Addison’s disease becomes very blurry. Symptoms are severe and can include:

  • Severe vomiting and diarrhea
  • Dehydration
  • Low blood pressure
  • Sudden severe pain in the abdomen, lower back, and legs
  • Loss of consciousness

An Addisonian crisis is rare, and most people will go to their healthcare professional at the first sign of symptoms. But in about 25% of cases, the symptoms will first appear in an Addisonian crisis. If not addressed, an Addisonian crisis may be fatal. The presentation of symptoms in an Addisonian crisis and in stage four AFS are very similar, even though their etiology may be different.

As a person with severe AFS progresses into stage four, the symptoms become more easily seen and more convoluted. The fatigue becomes nearly unbearable because the body remains unable to deal with the stresses that come every day. There may be multiple unusual paradoxical reactions that are unexpected.
Some of the symptoms common in this stage include:

  • Sudden onset of anxiety and feelings of impending doom when resting
  • Sudden onset of roller coaster blood pressure
  • Fatigue or malaise instead of calm when taking steroids
  • Wired and anxious feelings when taking vitamin C, adrenal glandulars, or herbs
  • Feeling more toxic instead of better after going through detoxification programs
  • Sudden onset of heart palpitations in spite of normal cardiac functioning
  • Being constipated instead of having loose stools when taking high doses of vitamin C
  • Feeling a sense of well-being after taking some nutrients, only to have a crash

From this, it is clear that the effects of stress are severe and wide reaching. However, as these effects reach the reproductive system, their effects are distinct and cause another series of symptoms.

Stage four of AFS is very serious and has similar symptoms to Addison’s disease. These symptoms can become fatal. The adrenal glands are totally exhausted at this stage.

Effects of Stress on the Female Reproductive System

When looking into the effects of stress on the reproductive system, it is first necessary to understand the normal processes involved in the female reproductive cycle. Beginning on the first day, the typical menstrual cycle takes about 28 days to complete. For the first five days, the lining of the uterus sloughs off, marking what is called the menses. Then the lining begins growing again until about the fourteenth day when ovulation takes place. If the egg generated during ovulation is not fertilized, the endometrial lining of the uterus will be shed again.

Normally, estrogen begins rising on the first day of the cycle and comes to a peak on the day of ovulation, day 14. If there is no fertilization of the egg, estrogen levels begin dropping until day 28. At the same time, progesterone begins rising about day 14. Once again, with no fertilization there is no need for increased progesterone since the uterus will not need it to help support the growing fetus. Therefore, progesterone begins decreasing as the menses comes on.
In the human reproductive system, the balance between estrogen and progesterone in females is essential. And this balance is not necessarily only dealing with absolute values, but also in terms of relative values. For example, it is normal for the levels of both estrogen and progesterone to decrease as women age. Even though both hormones decrease, the amount of decrease is greater for progesterone than for estrogen. Therefore, even if the absolute values of both are in the ‘normal’ range, a woman can still have a predominance of estrogen.

This is the beginning of a condition called estrogen dominance. This condition can start as early as the teens but is often not noticed that early.

There are a number of factors that play a role in the development of estrogen dominance. As mentioned above, there is the normal unequal loss of both estrogen and progesterone that can bring on a relative estrogen dominance. Also, women taking estrogen replacement therapy can develop the condition. In addition there are environmental factors, products that contain chemicals similar to estrogens, that can actually add estrogen to the body. These factors are called xenoestrogens.

Estrogen is a pro-growth hormone. It stimulates the growth of breasts, increases body fat, and triggers cancer cell growth. On the other hand, progesterone balances estrogen in a number of ways in the reproductive system and protects against breast cancer and fibrocystic breast disease.

Some symptoms of estrogen dominance include:

  • PCOS
  • Fibroids
  • PMS
  • Swollen fingers
  • Swollen breasts
  • Impatience
  • Endometriosis
  • Clots during period
  • Irregular or missed period
  • Fibrocystic breast disease
  • Breast cancer

Another factor to consider is that stress can lead to increased estrogen levels.

The hormone circuit and estrogen levelsAll hormone systems are interrelated so that what happens in one system affects all others. For example, as stress increases and becomes chronic the adrenals are not able to produce sufficient cortisol to meet the demand. Thus, a process known as “pregnenolone steal” takes place. Pregnenolone is a precursor hormone for all other hormones.

Pregnenolone is also converted into DHEA and other male hormones. Thus, if stress leads to the “pregnenolone steal,” there is less of it to be converted into male hormones as well.

When more cortisol is needed by the body to deal with the effects of stress, pregnenolone can be used more to make cortisol to meet the demand. What ultimately happens in this process is pregnenolone is converted into progesterone which is then converted into cortisol to help meet the increasing demand. Of course, this leaves less progesterone available to counter the effects of estrogen, leading to estrogen dominance.

This is one reason the symptoms of estrogen dominance are so often seen in women with adrenal fatigue due to chronic stress. As the severity of the adrenal fatigue increases, the severity of these symptoms will also increase.

Also when stress becomes chronic, the body begins to down-regulate processes that are not essential for the survival of the individual. This means processes such as reproduction are also down-regulated. This leads to a stopping of the menstrual cycle.

Other hormones are also necessary for the process of reproduction. The hypothalamus releases a hormone called Luteinizing Hormone Releasing Hormone (LHRH) that stimulates the pituitary to release two hormones called Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH). These two hormones stimulate the ovaries to mature the egg and get it ready for fertilization and to release estrogen to aid in the maturation of the egg.

Under stress, the hypothalamus decreases the amount of LHRH released. The increase in cortisol that comes with stress inhibits the release of this hormone. With less LHRH there is less LH and FSH.

Other mechanisms start up that guarantee the shutdown of the reproductive system. One of these mechanisms is the release of hormone signals that make the pituitary less sensitive to LHRH. Another is the release of glucocorticoids that cause the ovaries to be less sensitive to LH and FSH. A third mechanism is the release of prolactin that makes the uterine walls thinner.

In males, chronic stress has a negative effect on many of the reproductive functions as well. It affects testosterone production, the production and maturation of sperm, and can bring on erectile dysfunction and impotence.
With increased stress comes more vulnerability to infections. This includes infections of the prostate gland, testes, and urethra.

Another factor that increases the level of estrogen in the body is increased adipose tissue. When people develop more fat cells, as is often seen with adrenal fatigue as a result of stress, these adipose cells can also produce estrogen. This is one more way stress can lead to high levels of estrogen.

Another mechanism that can negatively affect the female reproductive system occurs when corticotropin-releasing hormone (CRH) released by the HPA axis decreases the amount of gonadotropin-releasing hormone (GnRH). Glucocorticoids released under stress decrease LH and secretion of progesterone and estrogen. CRH is also produced in peripheral inflammatory sites where it causes more inflammation.

CRH also regulates reproductive functions with an inflammatory component such as ovulation and implantation. It also helps in the beginning of labor and in the physiology of pregnancy. Placental CRH leads to the hypercortisolism seen in the latter half of pregnancy and the temporary adrenal suppression found postpartum.

Effects of stress on the reproductive system typically involve an increase in estrogen, possibly leading to estrogen dominance. Down regulation that occurs when the body is in the advanced stages of AFS can lead to the reproductive system essentially being shut down. This down regulation takes place as the body attempts to conserve energy by shutting down or limiting body systems that are not essential to survival of the individual. The reproductive system is one of those systems.

Effects of Stress on Pregnancy and Postpartum

Probably the first manifestation of stress affecting reproduction is infertility. In the case of severe chronic stress, the body will likely shut down the reproductive system because it is an energy conserving mode. Those systems not required for the survival of the individual will cease to function for a time. The reproductive system is one of those non-essential systems.

This shut-down will lead to amenorrhea, or lack of a menstrual cycle. This will not usually occur in young women, however, but infertility will.

In this situation, both ovulation and implantation are difficult. In vitro fertilization (IVF) is becoming increasingly sought after in such cases. Often, many attempts are necessary before a successful pregnancy. This is because the body is signaling that it does not want to become pregnant due to the effects of stress. However, this signal is often missed or ignored and IVF attempts continue.

With some women, those who have strong constitutions and are relatively young, IVF does work eventually. In spite of the difficulties and symptoms shown by their bodies, they successfully achieve pregnancy.

One of the problems that can then occur is a miscarriage in the first trimester. This comes down to the lack of progesterone available to the body for support of the fetus in the uterus. During chronic stress, there is less progesterone due to its conversion into cortisol to help fight stress. Thus, multiple miscarriages in the late first trimester might occur.

Much of the time, the cause of these multiple miscarriages is missed. Adrenal fatigue is not considered as a probable cause. However, with appropriate support of the adrenals at this time, the miscarriages should cease.

For those women successful in achieving pregnancy in spite of adrenal fatigue and its effects on reproduction, there may still be problems to face in maintaining the pregnancy past the first trimester.

Normally, the body would produce sufficient progesterone to support the fetus. This has a secondary positive effect also. The increased progesterone produces a calming effect. In many cases, women report pregnancy to be one of the best times of their lives and want to get pregnant again for this reason.

The hormone circuit and pregnancyThere are other women who don’t feel that pregnancy is such a wonderful time. They manage to get pregnant and keep the baby through the first trimester, but have a terrible time during the rest of the pregnancy. They feel tired, they struggle through the days, and they have to rest a lot. No one thinks about the adrenal glands being involved in this difficulty. Those who experience such a difficult pregnancy should consider the possibility that other problems are causing it.

Some women go to their healthcare professionals and are given a complete workup. Often, the thyroid is blamed and the woman is placed on thyroid medications. There is potential for problems here, however.

A significant problem may occur in those whose adrenal glands are already overburdened due to the demands of stress. Adding thyroid medications stimulates metabolism and increases the demand placed on the adrenals. This can result in even lower levels of progesterone due to its conversion into cortisol. Instead of taking care of a problem with the thyroid, this approach may actually worsen the already difficult pregnancy.

Much of the time, these women are told to go home and rest, just survive the rest of the pregnancy. They become more tired, suffer more fatigue, and have to drag themselves through their days. Eventually, the pregnancy is over and they have a new baby.

But postpartum, their difficulties are not over. They crash. They still have unresolved fatigue. Their energy doesn’t return. And if they’re breastfeeding they have the feeling of being drained all day every day.

Over the next few months, they continue to go downhill. Depression sets in. Sleeplessness begins. The fatigue worsens. Anxiety and panic attacks add to the toll. They are unable to deal with any stress.

In spite of rest, adrenal crashes begin occurring. Sometimes these crashes come in waves. There will be a crash, some recovery, maybe a short time of relief, then another crash. The postpartum adrenal crashes and continuing fatigue are another indication that the body was not taken good care of during the pregnancy. Progesterone has been depleted, and the mother continues being very tired and unable to take care of the baby. Things get progressively worse.

Much of the time, lab tests and examinations show normal results and the adrenals are not considered. Stress is not addressed adequately. The woman may be placed on medications to stimulate her system to work better, but nothing seems to work. Conventionally trained healthcare professionals may suggest antidepressants and refer women to mental health professionals.

It is important to pay attention to these signs when conventional lab tests come back negative. The body is saying there is something wrong. It is important to look at all potential causes and address whatever may be a cause of the crashes and fatigue.

When there is stress affecting the reproductive system, one of the first problems that will occur is infertility. Couples may turn to IVF, successfully become pregnant, then run into other problems. Typically, this is a lack of sufficient progesterone to sustain the pregnancy. First trimester miscarriages result. If the woman is successful in maintaining the pregnancy through the first trimester, other problems related to stress can crop up making the rest of the pregnancy difficult. Following birth, adrenal crashes and continuing fatigue may come into play.

Effects of Stress on the Thyroid

With the thyroid hormones so intimately involved in so many functions in the body, any change in their levels will be felt quickly. And with the close inter-relatedness of the thyroid with both the adrenal hormones and the reproductive hormones, anything that happens with one of the other hormone systems will affect the thyroid.

When the thyroid hormones become imbalanced, symptoms can become very confusing and difficult to understand. Remediation efforts must include evaluation of the adrenal and ovarian systems.

When stress affects the body, the adrenals are typically the first organ system stimulated. Cortisol is produced and released by the adrenals in an effort to fight the effects of stress. As stress continues and builds, the pressure on the adrenals to produce more cortisol also builds. Eventually, unless the stress is resolved, the adrenals become fatigued to the point of not being able to keep up with the demand.

Once this point is reached, the body begins shutting down systems in an effort to conserve energy. This down-regulation affects both the reproductive and thyroid systems. The reproductive system is not necessary for the survival of the individual and is thus shut down. The thyroid is affected through the body’s attempt to conserve energy by down-regulating metabolism. Since the thyroid hormones help regulate the metabolic processes of the body, its production and release of hormones is also down-regulated.

Thyroid binding globulin (TBG) increases as the thyroid is down-regulated. This decreases the amount of free T4 and free T3 in the bloodstream. At the same time, total T3 and T4 levels can be in the normal range.

What the body wants at this point, with chronic stress prevalent and the adrenals unable to produce and release sufficient cortisol, is to rest and conserve energy.

When the thyroid hormones are low, such as in this case, there will also be effects on the reproductive and adrenal hormones and the functioning of these two organ systems.

Thyroid functioning is affected by stress due to the inter-relatedness between it and the adrenals and reproductive systems. What affects one of these systems affects the others as well.

The Thyroid and the Reproductive System

The hormone circuit, the reproduction system and the thyroidThrough its regulation of metabolism, the thyroid affects the functions of the reproductive system. The thyroid’s influence on sex hormone binding globulin (SHBG), gonadotropin-releasing hormone (GnRH), and prolactin has effects on a woman’s ability to become pregnant and on her menstrual cycle. Progesterone production also is affected by thyroid hormones. There must be enough progesterone present for the support of the fetus in the uterus in order for the pregnancy to be viable. Infertility problems may be resolved when a woman’s sub-clinical hypothyroidism is resolved.

Any imbalance in thyroid hormones can also bring menstrual irregularities in both young and older women. Progesterone levels that are chronically low are often found in women who suffer from PCOS and infertility problems. If problems with thyroid hormones are not handled, they can add to infertility issues, menopause symptoms, and PMS.

Thyroid hormones also are similar to some metabolites of estrogen and progesterone, and thyroid uptake receptor sites can be inhibited or increased by estrogen and progesterone.

Symptoms of menopause are often mimicked by imbalances in T3 and T4 and imbalances in estrogen and progesterone. These imbalances often have adverse effects on energy, sleep, temperature regulation, fluid retention, and mood.

It is possible for women to be in a state of sub-clinical hypothyroidism and still have normal TSH values.

The thyroid and reproductive system hormones are closely related. Through its effects on the metabolic system, the thyroid has a certain regulatory function over the production of hormones that affect the reproductive system. This also has an effect on pregnancy and the viability of the pregnancy. Menstrual irregularities can be brought on by imbalances in thyroid hormones.

The Thyroid and the Adrenal Glands

The thyroid has a very close relationship with the adrenal glands as well as with the reproductive system. As mentioned previously, when the adrenals can no longer meet the demand for cortisol to fight the effects of stress, the body begins down-regulating multiple systems to conserve energy.

One way this affects the thyroid is the slowing down of the body’s metabolism. Doing this decreases the production of T3 and T4. Thyroid binding globulin (TBG) is increased resulting in less thyroid hormone available to the cells. While this is happening, the total T3 and T4 levels may be in the normal range.

Also, cortisol can negatively affect the conversion of T4 into T3, lowering the amount of thyroid hormone available to the cells.

At the same time, some of the available T4 is converted into reverse T3 (rT3). rT3 inhibits the functioning of T3. Even after the stress is resolved and cortisol production is back to normal, rT3 may persist in its presence and effects on T3. If this continues, the result may be rT3 dominance which leads to symptoms of hypothyroidism.

The thyroid and the adrenals are closely connected as well. When the adrenals become fatigued due to chronic stress, the body begins down-regulating some processes in order to save energy. One of those processes is metabolism which is greatly influenced by thyroid hormones. This leads to low levels of free T3 and T4 in the body. Cortisol itself negatively affects thyroid hormones.

Ovarian-Adrenal-Thyroid (OAT) Axis Issues

Tying in the three systems involved in the Hormone circuit of the NEM stress response is the OAT axis. The name of this system expresses the very close interrelationship among the ovaries, adrenals, and thyroid. These three systems are closely intertwined and dependent on each other for optimum functioning. What affects one, affects the other two.
As long as the hormones of the three systems work in balance, the Hormone circuit remains functional. But issues arise when stress triggers this circuit and becomes chronic.

When stress becomes chronic and the NEM stress response is activated, symptoms that develop indicating an OAT axis imbalance are such that they suggest a concurrent decompensation of all three systems in this circuit.
Often, the hormone symptoms that are reported are suggestive of adrenal fatigue, estrogen dominance, and hypothyroidism. Typical symptoms include:

  • Chronic fatigue
  • Joint pain
  • Insomnia
  • Diabetes
  • Dry skin
  • Brain fog
  • Exercise intolerance
  • Sleeplessness
  • Sugar intolerance
  • Endometriosis
  • PMS
  • Feeling cold
  • Slow metabolism
  • Inability to lose weight
  • Anxiety
  • Depression
  • Irregular menstrual cycles
  • Fibrocystic breast disease
  • Central obesity

These and other symptoms will typically be unique in number and severity with each individual.
Even women whose ovaries have been removed can still have OAT issues such as those listed above. This is because estrogen produced in other parts of the body is still present. The adrenal glands and adipose tissue are two other areas of the body that produce estrogen.

Since the current knowledge and understanding of OAT axis issues stems from case studies and clinical experiences, they should be considered as a clinical state and not a disease state. Conventional medicine does not fully accept or recognize this hormonal state irregularity. It can manifest as clinical or sub-clinical. There is no lab test that can definitively pinpoint imbalances in the OAT axis because of the multiple endocrine imbalances involved.

A similar combination of hormones in males is called the Adrenal-Thyroid (AT) axis. In this case, low libido and testosterone substitutes for ovarian imbalance. Low levels of androgens will also affect the thyroid and adrenal glands.

The thyroid and the adrenals are closely connected as well. When the adrenals become fatigued due to chronic stress, the body begins down-regulating some processes in order to save energy. One of those processes is metabolism which is greatly influenced by thyroid hormones. This leads to low levels of free T3 and T4 in the body. Cortisol itself negatively affects thyroid hormones.

The Adrenals and The OAT Axis

The OAT Axis and the hormone circuitThe sequence of pathways whereby the adrenals affect and are affected by the OAT axis begin with the adrenals being stimulated when stress hits the body. They are typically the first of the endocrine functions to break down when stress becomes chronic and overwhelms the body’s normal stress-fighting mechanisms. The adrenals become fatigued requiring typical, socially acceptable ways of masking early signs of fatigue, such as increasing the amount of coffee consumed.

The pancreas, particularly the insulin-producing part, is the next endocrine gland to be affected. A blood sugar imbalance typically follows with an attempt made by people to re-balance blood sugar by ingesting soft drinks, energy drinks, and sweets.

Following the pancreas, the thyroid gland is affected in this break down of functions. Feeling cold, weight gain, and sluggishness are typical symptoms. Hypothyroidism is a common assessment at this point with the use of thyroid replacement medications. Unfortunately, over time about 70% of people on this medication continue to be symptomatic.

Along with hypothyroidism symptoms come symptoms of estrogen dominance, such as irregular menstrual cycles, PMS, endometriosis, and lumpy breasts. These symptoms are often handled with hormone replacement medication that may help temporarily.

Over time, the autonomic nervous system, hypothalamus, parathyroid glands, and pineal gland become affected. By this time the OAT axis is severely out of balance.

In this sequence, adrenal fatigue is typically the last possible origin of the symptoms to be considered. By that time, the thyroid and ovarian hormone imbalances may be severe. Much of the time, the involvement of the thyroid and ovarian systems are not considered in any intervention efforts.

Because of their control of cortisol, the adrenal glands hold the key to this series of hormonal imbalances. When the adrenals become fatigued and cortisol becomes imbalanced in the body, this sets in motion multiple organ resistances, including the thyroid and ovaries. Secondary or sub-clinical hypothyroidism is often a result of adrenal fatigue.

With complaints of dry skin, fatigue, and weight gain, typical symptoms of hypothyroidism, and patients are given thyroid replacement medication. After the temporary improvement that is usually seen is over, even more medication may be given. This pushes the body into metabolic overdrive, often uncovering pre-existing adrenal weakness. This increases adrenal fatigue and often triggers an adrenal crash. With conventionally trained health professionals running out of options, antidepressant medications may be given. These usually served to worsen the OAT imbalance.

The cortisol produced and released by the adrenals affects other hormones and hormone-regulated organ systems such as the ovaries, thyroid, and pancreas. Many hormones are reduced to sub-optimal levels. Normal negative feedback loops are inhibited and binding carrier hormones are disrupted.

The hormones affected are unable to affect their target organs to achieve homeostasis. Both blood pressure and blood sugar can become erratic. Brain fog becomes prevalent. Metabolic function slows, bipolar and anxiety states crop up, menstrual flow becomes irregular, and reactive adrenaline rushes occur uncontrollably.

The Thyroid and the OAT Axis

As is the case with all three systems in the hormonal circuit and their hormones, what affects one affects all. This was seen in the discussion of the adrenals above. The same is true with the thyroid.

Because of its intricate relatedness through the OAT axis, the thyroid affects the ovarian and adrenal systems. The reproductive gland activities are influenced by the thyroid through its effects on metabolism.

The effects of the thyroid hormones on the production of progesterone, in particular, affect whether a woman becomes pregnant and sustains that pregnancy.

In its close relationship with the adrenals, the thyroid is affected by the down-regulation of body systems seen in advanced adrenal fatigue. Down-regulating the thyroid leads to slower metabolism that then affects the reproductive glands.

This kind of down-regulation of the thyroid can lead to a false assessment of hypothyroidism and the corresponding medications. This serves to speed up the metabolism, placing increased pressure on the already weak adrenals and worsening adrenal fatigue.

The Reproductive Glands and the OAT Axis

When the levels of estrogen and progesterone are in balance, a woman’s reproductive system is poised to work as it is supposed to. However, due to a number of causes, these hormones can become imbalanced.

This kind of imbalance typically involves a higher level of estrogen compared to progesterone. As women age, a loss of both hormones is normal. However, this loss is not equal. Typically, more progesterone is lost compared to estrogen. This leaves the woman with at least a relative estrogen dominance.

High levels of estrogen curtail the effects of thyroid hormones as well as the effectiveness of cortisol. These effects lead to hypothyroidism and added pressure on the adrenals. When the thyroid and adrenals are negatively affected by estrogen dominance, they increase the effects of estrogen dominance.

The OAT axis is composed of hormones from each of the systems involved in the hormone circuit of the NEM stress response. An imbalance in the hormones of one of these systems leads to problems in the other two systems.

Signs and Symptoms of A Dysfunctional Hormone Circuit

When the Hormone circuit of the NEM stress response model becomes dysfunctional, there are a multitude of signs and symptoms that appear. The rest of this article will address some of those signs and symptoms in detail.

Estrogen Dominance

A significant increase in numerous conditions among women has become obvious over the past four decades. Some of these conditions include:

  • PMS increasing to affect nearly 30% of perimenopausal women
  • Breast cancer being found in almost 10% of all women
  • Endometriosis being a problem in 10% of perimenopausal women
  • Uterine fibroids in about 25% of women between the ages of 35 and 50

Much of the time these conditions have been inadequately assessed and remediated. Current research has shown the underlying connection among all of them to be estrogen dominance. This situation is one in which the level of estrogen in the body is relatively high, while the level of progesterone is extremely low. Almost half of the women in developed countries over the age of 35 are afflicted by estrogen dominance.

Typical complaints from women with estrogen dominance include:
Estrogen dominance and the hormone circuit

  • Swollen, enlarged breasts
  • Inability to wear rings
  • Cramps
  • Irregular periods
  • Periods that come and go
  • Impatience
  • Bossiness
  • PMS
  • Large clots during menses leading to concern
  • Fibroids
  • Endometriosis
  • Fatigue
  • Breasts hurting when hugged
  • Can’t fit into shoes
  • Cysts in the breasts

Ideally, estrogen and progesterone work in balance with one another to reach hormonal harmony in both sexes. The problem with an imbalance is not the absence of either estrogen or progesterone, but rather, a relative dominance of estrogen and relative lack of progesterone.

Normally, the levels of estrogen and progesterone decline with age. However, during the perimenopausal and menopausal times, the decline becomes very significant in women.

But this decline is not balanced. During the ages of 35 to 50, there is a 75% decline in progesterone but only a 35% decline in estrogen. By the time of menopause, the level of progesterone in the woman’s body is extremely low, while estrogen remains at about half of its premenopausal level.

This gradual decrease in estrogen levels but extreme drop in progesterone levels leaves women with too little progesterone to counter the effects of estrogen. From the mid-thirties to mid-forties, many women suffer from this predominance of estrogen. After age 50, essentially all women suffer from this condition. The end result of a relative excess of estrogen over progesterone is the condition called estrogen dominance.

To give some idea of the seriousness of this situation, the optimum progesterone to estrogen ratio should be 200 to 300 to 1. Considering progesterone to be exceptionally low in estrogen dominance, these numbers could be reversed.

Another indication of the seriousness of estrogen dominance is seen in the conditions it may cause. Some of these conditions are:

  • PMS
  • Breast cancer
  • Fibrocystic breast disease
  • Endometriosis
  • Endometrial polyps
  • PCOS
  • Infertility
  • Autoimmune disorders
  • Low blood sugar
  • Menstrual pain

Women who live in non-industrialized countries and still rely on whole foods suffer less of a deficiency in progesterone and have fewer instances of estrogen dominance.

Causes of estrogen dominance are the typical conditions faced in modern industrial society. Over the past several decades, the typical Western diet has gone from consisting of mostly whole foods to highly processed fast foods. Some of the sources of chemicals that help lead to estrogen dominance include:

Animal Products. Prior to the last 70 years, cattle ate grass and natural organic feed and chickens were free-range. Now, animals that supply the meat in stores are typically raised in deplorable conditions in cages and fed hormone-laced processed feed. These types of feed, along with the pesticides that are typically used on factory farms, have estrogen-like properties. When these animals eat this feed, these properties are passed on to consumers.

Plant Products. A huge amount of pesticides, herbicides, fungicides, and other biocides are used on food crops in the U.S. every year. Many of the pesticides are known to be hormone disruptors. In addition to these chemicals lingering on the plant foods ingested in this country every day, they also have been added to the environment in other ways. Fruits and vegetables grown in other countries and imported here to be served at the family dining table may have been treated with illegal chemicals such as DDT as well. The residues from many pesticides have chemical properties much like estrogen.

Xenoestrogens in the Environment. Ovarian follicles in developing female fetuses in the womb are very sensitive to environmental chemicals that have some of the same properties as estrogen. While the mother may show no outward signs or symptoms of this exposure, the developing baby may. These signs and symptoms may not surface until the baby reaches puberty and incomplete ovulation or insufficient progesterone production may be seen. These xenoestrogens can be found in a multitude of products and environmental toxins around people every day.

Industrial Solvents. Some of the xenoestrogens can be found in these solvents that are in many commonly-used products in every household. Things like fingernail polish remover, paint thinners, carpet, cleaning products, and insect sprays are just a few of the sources of these xenoestrogens. They enter the body and begin accumulating over time in the myelin sheath that surrounds the nerve cells and in adipose tissue.

Chronic Stress. Over time the effects of chronic stress lead to exhausted adrenal glands and reduced production of progesterone. With decreased levels of progesterone, relative levels of estrogen increase.

Obesity. Adipose tissue, found in higher levels in obese people, contains an enzyme that is used to convert adrenal steroids to estrogen. With the dramatic increase in obesity in this country, this becomes a huge source of estrogen that can lead to estrogen dominance.

Vitamin Deficiencies. In general, people in this country live with serious deficiencies in vitamins. Vitamin B6 and magnesium are essential in neutralizing estrogen in the liver. Increased levels of estrogen tend to lead to deficiencies in the B vitamins, zinc, and magnesium.

Caffeine. The intake of caffeine from all sources has been linked with higher estrogen levels regardless of age, body mass index, smoking, caloric intake, alcohol consumption, or ingestion of cholesterol.

Dangers of Estrogen Dominance

Some of the dangers of estrogen dominance include the increase of thyroid-binding proteins in the blood. This may lead to a state of subclinical hypothyroidism in which lab tests show normal results, but the levels of thyroid hormone in the blood are low. Severe cases of estrogen dominance can lead to secondary hypothyroidism. High levels of estrogen inhibit the adrenal cortex in its responses to signals from the brain. This means the brain may be signaling for increased cortisol production, but the high estrogen levels blunt the response from the adrenals. Estrogen also interferes with the release of cortisol from the adrenal cortex. Cortisol-binding globulin increases with increases in estrogen. This means less cortisol available in the bloodstream because of this globulin binding with cortisol and making it inactive. Total cortisol in the blood may be in the normal range, but free cortisol is insufficient. Only free cortisol can enter the cells and activate receptors there.

In the same way that estrogen dominance can lead to adrenal insufficiency, so also does adrenal insufficiency lead to estrogen dominance. In the adrenal cortex, cortisol is made from progesterone. When the adrenals are in a weakened state, less progesterone is produced in favor of cortisol. This leads to a deficiency in progesterone and a relative dominance of estrogen. This process thus produces a vicious cycle.

Estrogen dominance is possibly the most common indicator of a dysfunctional hormone circuit of the NEM stress response. There are many causes of estrogen dominance, including the natural tendency to the condition due to aging. Normal aging brings about greater decreases in progesterone compared to estrogen, resulting in at least a relative estrogen dominance. However, stress also is a culprit. With increasing stress, progesterone is converted into cortisol, further increasing the risk of estrogen dominance. With estrogen dominance comes more stress on the adrenals, increasing the risk of adrenal insufficiency.

Breast Cysts

A lump in the breast is a very common cause for women to go to their gynecologist. The vast majority of breast lumps are not cancerous.

What they are is the body’s signal that more progesterone is needed. Estrogen stimulates the proliferation and growth of breast cells. The fibrocysts found by women in their breasts are overgrowths of normal breast tissue. It is an early signal that estrogen dominance is beginning and more progesterone is needed to balance it.
The excess estrogen may be a result of the normal process of losing more progesterone than estrogen leading to relative estrogen dominance. Or it may be an indication of increasing estrogen from one of the many sources mentioned earlier in this article.

The development of breast cysts is another indicator of dysfunctional hormone circuit. Once again, estrogen plays a major role in the development of these cysts. The excess estrogen may be due to normal aging or to continuing and chronic stress.

Cancer

The hormone circuit and cancerBreast cancer is the number one cancer killer among women between the ages of 45 to 50 and is the most common cause of death in women between the ages of 18 to 54. Prior to the increased popularity of estrogen replacement therapy, breast cancer struck 1 in 30 women on average. Now, it strikes 1 in 9 women.

Breast cancer comes in many forms. About 90% of cancers start in the milk ducts or glands while 10% begin in fatty or connective tissue.

In situ carcinomas are found entirely in a milk duct with none in the surrounding tissue. This type of breast cancer makes up about 15% of them.

A very large percentage of breast cancers are called ductal carcinoma in situ (DCIS). Usually, these cancers are local when found but are considered a precursor to invasive cancers. Mammograms are usually successful in finding these cancers.

A more difficult to identify type of breast cancer found usually in pre-menopausal women is lobular carcinoma in situ (LCIS). It is more difficult to find because it does not form a palpable mass. Around 25% of women with LCIS develop invasive carcinoma. It is low in virulence, often not becoming invasive for up to 40 years after initially being found. The breast cancer with the worst prognosis is invasive ductal and lobular carcinomas. These cancers spread quickly.
Research has shown FDA-approved estrogen replacement medications to be carcinogenic. One study from Harvard Medical School showed women who took estrogen and a synthetic progesterone drug to have an increased risk of developing breast cancer of between 32% and 46%. This increase was shown to be most likely after taking the medications for 10 years.

However, more recent research has shown a 20% increase in risk after only four years of use and a 40% increase in risk if both estrogen and progesterone were taken.

These studies indicate that synthetic progesterone is not what the body needs as a replacement. Rather, it needs natural progesterone. And, in addition to breast cancer, there appears to be an added increased risk of developing uterine or ovarian cancers.

The peak time for developing breast cancer appears to be about five years prior to menopause. This is a time when the progesterone in the woman’s body has begun its very significant decline leaving her in a state of at least relative estrogen dominance. Anovulation resulting in lower progesterone levels already appears to be a major contributor to estrogen dominance. Stress and prenatal exposure to xenoestrogens are other major causes of anovulation. Numerous studies have shown the majority of breast cancers to be non-genetically linked. Studies have also shown up to 80% of breast cancers are caused by estrogen dominance.

Providing sufficient progesterone to counter the effects of estradiol on breast cell proliferation may be a major step toward decreasing the risk of developing breast cancer. Estradiol increases breast cell proliferation by two hundred and fifty percent while progesterone decreases this proliferation by over four hundred percent.

The development of cancer in the breasts, ovaries, or uterus may be another sign of a dysfunctional hormone circuit. Estrogen is the culprit in many of these cancers. Excess estrogen prompts the growth and proliferation of breast cells that may then turn cancerous.

Estrogen Deficiency

While estrogen dominance is a clear indicator of a dysfunctional Hormone circuit, so is estrogen deficiency. As discussed before in this article, both progesterone and estrogen naturally decline with age. Once women reach the postmenopausal period of their lives, there is a chance they can develop an estrogen deficiency.

This is important due to the neuroprotective function of estrogen. As more and more women live longer, they will spend a longer period of time post-menopause. Since this means living longer with a potential estrogen deficiency, it also means the risk of stroke and/or developing other neurological disorders increases.

They will be living longer without the neuroprotective function performed by estrogen, especially on the hypothalamic hormones. These hormones produced or stimulated by the hypothalamus serve a protective function against cerebrovascular accidents. Thus, the risk of stroke increases as women reach menopause.

Following menopause, the results of stroke among women are more serious than those among men. The rates of fatality or disability are greater for women after menopause. This indicates the protective function of estrogen and other hypothalamic hormones decreases significantly in women.

Results of animal studies in this area show stroke results to be dramatically more severe. This appears to be due to the effects of estrogen directly on the brain rather than any effect on blood flow.

One example of the neuroprotective function of estrogen on the brain is the work of E2. The ovarian hormone 17beta estradiol (E2) is the most active form of estrogen. Its presence decreases the effects of stroke faster because it can work independently of the estrogen receptors in the brain.

E2 has significant influence on the brain functions that are most impaired following a stroke, such as memory formation, cognition, and motor coordination. It not only limits the damage to these areas following a stroke, but also enables the brain to repair and remodel itself post-stroke.

The neuroprotective role of estrogen is also seen in its influence on some of the brain regions most affected by Alzheimer’s. The loss of this influence due to declining levels of estrogen in the aging brains of both males and females may play some part in the development of this condition.

The hormone circuit and Alzheimer'sAlzheimer’s has been shown to be the major cause of age-related dementia and is the reason underlying about 50% of dementias. Alzheimer’s typically starts in middle age and later, and it involves a complex combination of cognitive skills, functional skills, and decreasing hypothalamic hormones that include varying types of behaviors of different severities.

In addition to dementia, there are physical changes in the brain with Alzheimer’s. Atrophy, intracellular neurofibrillary tangles, granulovacuolar cytoplasmic changes, loss of neurons, and extracellular plaques containing beta-amyloid peptides are frequently seen.

At this point, about three times more women than men suffer from Alzheimer’s. This would seem to indicate a connection between menopause and the loss of estrogen and its protective function and the development of Alzheimer’s. Research into this possibility has shown mixed results.

One factor that may play a part in these mixed results is the bioavailability of estrogen. If there are sufficient levels of estrogen in the blood, but it is not available for use by the body, the results are the same as if the estrogen levels are low.

Much of the estrogen in the bloodstream is bound to the sex hormone binding globulin (SHBG). SHBG is a hypothalamus hormone. This type of estrogen will not cross the blood-brain barrier and thus is not effective in a neuroprotective way in the brain. Some studies have found an increase in the risk of developing Alzheimer’s with low bioavailable estrogen and high SHBG post-menopause. Other research has found the opposite. This suggests the need for much more research in this area.

Estrogen deficiency can also be a sign of a dysfunctional hormone circuit. Much of the time, this condition comes with the natural process of losing estrogen as women age. The larger problem that comes with estrogen deficiency is the loss of the neuroprotective function of estrogen. This increases the risk of stroke and/or of developing serious dementias such as Alzheimer’s.

Fibroids

Essentially benign tumors composed of fibrous tissues, fibroids are not rare in women. Many women have them. Some grow very slowly, others more quickly. Regardless of which of these women develop, estrogen is the driving cause behind fibroids.
Symptoms of fibroids include:

  • Leg or back pain
  • Difficulty urinating
  • Constipation
  • Heavy menstrual bleeding
  • Frequent urination
  • Pain or pelvic pressure
  • Prolonged menstrual bleeding

There are several kinds of fibroids, including:

  • Submucosal fibroids grow inside the uterus and may cause problems getting pregnant.
  • Subserosal fibroids grow outside the uterus and may press on the bladder or rectum leading to urinary problems or back pain.
  • Intramural fibroids grow in the muscles of the uterine wall and may lead to pain, pressure, or prolonged or heavy menstrual bleeding.

While it is unclear exactly what causes fibroids, there does appear to be a genetic component as well as the involvement of estrogen. Indeed, fibroids have been called a red flag indicating estrogen dominance is present.

The development of fibroids is another indication of a dysfunctional hormone circuit. These cause a multitude of physical problems including pain, heavy menstrual flow, and prolonged menstrual flow. While their cause is unclear, estrogen dominance is typically present.

Infertility

Infertility, the inability to get pregnant, is another sign of a dysfunctional Hormone circuit.

The causes of infertility are many, affecting 10-15% of couples in this country. Causes may be specific to the male, specific to the female, or more to the couple together.

Adrenal fatigue is being investigated more as a cause of infertility. One reason for looking to the concept of adrenal fatigue in this way is that many women who complain of an inability to get pregnant also complain of significant fatigue. With no clear reason for their inability to get pregnant, attention turns to the source of their fatigue.

Adrenal fatigue may be contributing to infertility due to lowered levels of estrogen and progesterone often encountered with adrenal fatigue. In order for pregnancy to occur, there must be sufficient female hormones to produce a fertile egg and to prepare the uterus for sustained pregnancy.

The ovaries produce many of the female hormones necessary for pregnancy, but the adrenals also play a role. Weakened adrenals lead to insufficient levels of hormones necessary to become pregnant and to sustain a pregnancy.

Some potential causes of adrenal fatigue before or early in pregnancy include:

  • Stress
  • Poor nutrition
  • Recent surgery
  • Infections
  • Lack of vitamins or minerals
  • Use of supplements that might negatively affect the adrenals

With adrenal fatigue, the uterus may not accept the fertilized egg due to a lack of essential hormones to sustain the pregnancy. Progesterone deficiency is typically the reason for this rejection.

The mechanism appears to be that, as stress increases, the Hormone circuit of the NEM stress response becomes dysfunctional. For younger people in this state, PCOS, PMS, endometriosis, and then infertility develop. For older people, estrogen dominance, OAT axis dysfunction, and adrenal fatigue become severe. The body shuts down those systems that are not necessary for the survival of the individual and infertility develops due to amenorrhea.

Younger women face difficulty in getting pregnant because ovulation is difficult due to low levels of estrogen, and implantation is hard due to low levels of progesterone. This leads many people to attempt in vitro fertilization (IVF). After several attempts, the woman may become pregnant, and the body, even though it doesn’t want to, may be able to sustain the pregnancy.

Infertility is often encountered as a result of a dysfunctional hormone circuit. The lack of female hormones to produce a fertile egg and to sustain a pregnancy are often the culprits. These hormone levels are low due to an increase of stress that leads to adrenal fatigue.

Low Libido

Low libido and the hormone circuitLow libido, or sex drive, is one of the most common symptoms of adrenal fatigue. When the body is stressed to the point of developing adrenal fatigue, the body systems that are not considered essential for the survival of the individual are down-regulated, often to the point of shutting down completely. Reproduction is not essential for the survival of the individual, thus a person loses the drive to have sex.

When it is at the point of shutting down these non-essential systems, the body is in an energy conserving mode. Large amounts of energy are directed to the heart and circulatory systems because of their importance. The same is true of the brain and nervous systems. But the reproductive system is not essential for the survival of the individual.

Low libido as an indicator of a dysfunctional hormone circuit comes as a result if it not being essential to the survival of the individual. When the body is stressed to the point of adrenal fatigue, it goes into an energy conserving mode and shuts down these non-essential body systems.

Menopausal Metabolic Syndrome

The development of menopausal metabolic syndrome (MMS) shows the existence of a dysfunctional Hormone circuit. Many women are not aware of the potential for developing MMS at the time of menopause.

It is at this time of life that the decrease in estrogen that comes with age also signals an increase in androgens. This results in a significantly increased risk of weight gain, onset of type 2 diabetes, high blood pressure, low HDL cholesterol, high triglycerides, increased cardiovascular risk, and abdominal obesity.

Weight gain is often brought on with the decreased estrogen and increased androgens. A redistribution of fat from the subcutaneous and gluteofemoral regions centers in the abdomen.

One of the most common causes of this weight gain is changes in the hypothalamus which is directly affected by the loss of estrogen. It is the hypothalamus that regulates obesity.

In addition, the regulation of food intake by the central nervous system is also affected by the loss of estrogen. This may lead to the ingestion of too many fats and carbohydrates. Increased ingestion of these substances leads to increased insulin secretion and accumulation of fat.

Metabolic syndrome also affects the adrenals. It tends to change the individual’s emotional state and lowers the ability to fight stress. This leaves the body open to a number of illness conditions. Among these conditions is adrenal fatigue. One part of the adrenals’ functions in the body is aiding in the regulation of metabolism. Metabolic syndrome adds significantly to the stress on the adrenals due to increasing the difficulty of regulating metabolism. Working harder to attempt to balance the metabolism may lead to adrenal fatigue in the long run.

Menopausal metabolic syndrome occurs in most women as they enter menopause. It may also be an indicator of dysfunctional hormone circuit. The imbalance in hormones available to women at this time of life becomes more significant if the hormone circuit is dysfunctional.

Polycystic Ovarian Syndrome

PCOS, polycystic ovarian syndrome, becomes a problem with a dysfunctional Hormone circuit. One of the causes of this condition may be higher than normal levels of circulating androgens.

PCOS is a condition that involves multiple cysts on the ovaries. Along with these cysts are found symptoms such as anovulation, menstrual abnormalities, male pattern baldness, hirsutism, acne, and obesity. Also associated with PCOS are high triglycerides, insulin resistance, increased risk of type 2 diabetes, and low bone density.

With a stoppage or disruption of a woman’s normal ovulation cycle, PCOS can develop. This creates an imbalanced relationship between a woman’s brain, hormones, and ovaries.

Normally, the hypothalamus works to regulate hormones released by the ovaries and the synchronization of the menstrual cycle. The hypothalamus secretes gonadotropin-releasing hormone (GnRH) at the end of the menstrual cycle. This stimulates the pituitary to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). These two hormones stimulate production of estrogen and the maturation of eggs in the follicles.

When ready, one of the follicles will release its egg into the fallopian tube where it travels into the uterus. In the uterus, the egg converts into a corpus luteum, basically a factory for producing progesterone. It can raise the progesterone level to 200-300 times higher than the levels of estradiol.

The increased progesterone stimulates the lining of the uterus to get ready to receive a fertilized egg. It also stops ovary production for the time being. If fertilization doesn’t occur, the corpus luteum stops producing estrogen and progesterone, the uterus lining sheds off in the process of menstruation, and the process begins all over again.

PCOS occurs when there is not a successful ovulation. The follicle doesn’t release the egg that has developed. It then may turn into a cyst resulting in no progesterone development. This lack of progesterone is detected by the hypothalamus. It then works to stimulate the ovary to produce eggs by releasing more GnRH. The ovary is stimulated to produce more estrogen and androgens by increased LH and FSH from the pituitary. If the follicles still don’t produce mature eggs, more cysts can develop. This leaves the cycle dominated by estrogen and androgens without sufficient progesterone. This imbalance is the root of PCOS.

Polycystic Ovarian Syndrome or PCOS can develop when the normal menstrual cycle of a woman is disrupted by anovulation. The follicles that fail to release eggs can then develop into the multiple cysts that mark the condition. A relative dominance of estrogen and androgens versus progesterone is a root cause of PCOS.

PM Slump

A lack of energy that occurs around 3 p.m. may be an indication of a dysfunctional Hormone circuit. This lack of energy, or a PM slump, is normal due to the natural circadian rhythm of the body. Normally, this slump doesn’t require a nap. Consuming too many carbohydrates at lunch may also trigger the slump to occur closely after eating.

If a person doesn’t eat a lot of carbs for lunch and the PM slump becomes more significant, there may be another reason at work. The PM slump may be due to unregulated glucose levels due to a lack of cortisol. The lack of cortisol may be due to adrenal fatigue. When the afternoon rolls around, your blood sugar drops, and you feel tired.

When this slump is due to adrenal fatigue, brain fog and increased irritability may occur. After a short nap and consuming a snack, the energy level returns.

A lack of energy called a PM slump often occurs with a dysfunctional hormone circuit. Typically, it occurs around 3 p.m. and requires a nap with some kind of snack to build up the energy level once more. This condition may be due to a low level of cortisol when adrenal fatigue is present.

PMS

The hormone circuit and PMSPremenstrual syndrome, PMS, is related to estrogen dominance. A number of symptoms mark this condition. Some of them are:

  • Water retention
  • Fatigue
  • Emotional instability
  • Breast inflammation
  • Magnesium deficiency

Typically, these symptoms begin after ovulation and before the beginning of the menstrual cycle. Duration of the condition is from a few days to a couple of weeks with variable severity of symptoms. In general, the symptoms grow in severity prior to the menstrual cycle.

Some of the causes of PMS include:

  • Progesterone deficiency
  • Estrogen dominance
  • Hypothyroidism
  • Adrenal fatigue
  • Low fiber diet
  • Xenoestrogen exposure during embryo life

Fatigue

Fatigue is one of the major signs and symptoms of adrenal fatigue. When chronic stress hits the body and the adrenal glands become overburdened with the demand placed on them for more and more cortisol to fight the effects, fatigue develops. This is the kind of fatigue that doesn’t go away with rest. Often with adrenal fatigue, a person can sleep all night and wake up tired. Even though they may also nap in the daytime, fatigue is still present.

An imbalance of hormones in any one of the three systems that make up the Hormone circuit of the NEM stress response will result in fatigue for the person suffering from it. With the inter-relatedness of the three systems, whatever causes an imbalance of hormones in one system will often result in a corresponding imbalance in the other systems.

For example, a weakened adrenal system can lead to estrogen dominance and an imbalance in thyroid hormones. Likewise, either of the other two problems can lead to pressure on the adrenals that increases adrenal fatigue.

When the adrenals are stressed to the point of being unable to produce sufficient cortisol to fight stress effects, fatigue is one of the results. This is an indicator of a dysfunctional hormone circuit.

Summary

The Hormone circuit of the NEM stress response is the first of the circuits to be stimulated when stress hits the body. It is made up of the adrenal glands, the thyroid gland, and the reproductive glands. These three organ systems are interrelated such that what affects one affects all. These effects can be physiological, sub-clinical, or clinical in nature.
For example, if the adrenal glands become weak or fatigued, there is often concurrent malfunction of the thyroid gland and irregularity of the menstrual cycle. If the thyroid is less active, it tends to exacerbate adrenal fatigue. If there is ovarian hormone imbalance, such as estrogen dominance, any pre-existing hypothyroidism may be exacerbated.

The Ovarian-Adrenal-Thyroid (OAT) axis is the major pathway for the hormones of this circuit to work. If the OAT axis becomes imbalanced, one of the systems involved becomes clinically dominant. These imbalances, when they occur, are not typically equal across the three systems. Most of the time, the system that is damaged the most and is constitutionally weakest becomes the clinically dominant system.

Those individuals who are thyroid dominant typically suffer from severe low energy, dry skin, and inability to lose weight. Individuals who are adrenal dominant typically present with fragile emotions, such as irritability and anxiety. Those who are ovarian dominant will present most of the time with memory loss and brain fog, along with symptoms like PMS.

The adrenal glands are triggered by signals from the hypothalamus and pituitary to respond with the production and release of stress-fighting hormones, primarily cortisol, to deal with the effects of stress. When the stress continues and the adrenals become overwhelmed by the demand for cortisol, adrenal fatigue can set in.

The reproductive system, made up of the ovaries in females and the testes in males, are another component of the Hormone circuit. The two primary female hormones, estrogen and progesterone, work in balance with one another to keep the female reproductive system working as it should. Problems arise when estrogen becomes dominant in the system. This is true not only with absolute values of the two hormones, but also when estrogen becomes relatively dominant as with aging. When stress is chronic, the level of progesterone will typically decrease because so much progesterone is converted into cortisol to meet the demand for this stress fighting hormone. Also, with increasing levels of severity of adrenal fatigue, the body may ultimately shut down non-essential body systems, one of which is the reproductive system. This is an effort by the body to conserve energy.

Thyroid hormones play an important role in just about all body systems, particularly through its regulation of the metabolic rate. The intricate relationship of the thyroid with the adrenal and ovarian systems is shown clearly in its role in regulating metabolism. In this process, the thyroid affects the activities of the reproductive glands. Its effects on the menstrual cycle and the ability to get pregnant come through its influence on the production of sex hormone binding globulin (SHBG), gonadotropin-releasing hormone (GnRH), and prolactin. Progesterone production in the ovaries is also influenced by the thyroid. Progesterone is important for pregnancy because it provides a supportive environment in the uterus for the egg. Too little progesterone will result in no pregnancy.

The hormone circuit and thyroid hormonesJust as there is a close connection between the thyroid and the ovarian system, this same kind of close relationship exists between the thyroid and the adrenals. Under conditions of chronic stress, the adrenals become fatigued and ultimately the body begins shutting down some processes in order to conserve energy. This conservation of energy demands less work and more rest for the body. The body is metabolically slowed at this point. Since one of the functions of the thyroid is regulating metabolism, there is a significant effect on the thyroid.

As this slowdown occurs, the production of T3 and T4 is reduced. At the same time, there is an increase in thyroid-binding globulin (TBG). This results in more of the thyroid hormones being bound and thus unavailable for the cells. Another result is lowered free T4 and T3 in the body even though tests may show normal levels of total T4 and T3.
Cortisol levels are typically high when the body is under stress. Cortisol is able to inhibit the conversion of T4 into T3 and may also inhibit the hormones’ entry into cells.

Hashimoto’s thyroiditis is often mistakenly assessed as the reason for lowered thyroid hormones rather than seeing the inter-relationship among the ovarian, adrenal, and thyroid systems. Hashimoto’s is caused by an overly aggressive immune response in which the immune system cells begin attacking the thyroid gland.

Although the exact causes of Hashimoto’s are not known, there does appear to be a genetic component. The condition runs in families. Thyroid-specific genes such as the TPO genes and the thyroglobulin genes appear to be involved. Even with a genetic predisposition to the condition, a person may not develop the condition. Environmental triggers are needed in order to stimulate the genes involved into developing Hashimoto’s.

The effects of stress on the adrenals is clear. Their initial stimulation through chemical messengers from the hypothalamus and pituitary leads to increased production and release of cortisol and other stress-related hormones. With increasing and continuing stress, the demand for cortisol becomes so great that the adrenals cannot keep up. This is the beginning of Adrenal Fatigue Syndrome (AFS).

There are four stages of AFS, increasing in severity of symptoms. Initial symptoms in Stage 1 are mild and handled in socially acceptable ways such as drinking more coffee to get started in the mornings.

Stage 2 of AFS is when the stress level increases and becomes chronic, and the adrenals can’t keep up with the demand placed on them. Fatigue is more frequent, and rest doesn’t seem to help. Symptoms such as anxiety, PMS, and sleeplessness become common.

Stage 3 of AFS is divided into four phases to help clarify the symptom picture. A worsening of the symptoms seen in stages one and two begin the downward spiral of decompensation and dysfunction seen in this state. People can experience symptoms of some or all of these phases at the same time. Increasing severity of symptoms is seen in each phase.

Stage 4 of AFS is very serious and has similar symptoms to Addison’s disease. These symptoms can become fatal. The adrenal glands are totally exhausted at this stage.

Effects of stress on the reproductive system typically involve an increase in estrogen, possibly leading to estrogen dominance. Down-regulation that occurs when the body is in the advanced stages of AFS can lead to the reproductive system essentially being shut down. This down-regulation takes place as the body attempts to conserve energy by shutting down or limiting body systems that are not essential to survival of the individual. The reproductive system is one of those systems.

Thyroid functioning is affected by stress due to the inter-relatedness between it and the adrenals and reproductive systems. When stress becomes chronic and the body is conserving energy, one of the functions of the thyroid – regulating the metabolic system – comes into play.

Through its regulation of metabolism, the thyroid affects the functions of the reproductive system. The thyroid’s influence on sex hormone binding globulin (SHBG), gonadotropin-releasing hormone (GnRH), and prolactin has effects on a woman’s ability to become pregnant and on her menstrual cycle. Progesterone production also is affected by thyroid hormones.

The thyroid and the adrenals are closely connected as well. When the adrenals become fatigued due to chronic stress, the body begins down-regulating some processes in order to save energy. One of those processes is metabolism which is greatly influenced by thyroid hormones. This leads to low levels of free T3 and T4 in the body. Cortisol itself negatively affects thyroid hormones.

The Ovarian-Adrenal-Thyroid (OAT) axis covers the inter-dependent hormonal systems of the Hormone circuit of the NEM stress response. Because of their inter-relationships, what affects one, affects all. Significant symptoms develop when the OAT axis becomes imbalanced.

The cortisol produced and released by the adrenals affects other hormones and hormone-regulated organ systems such as the ovaries, thyroid, and pancreas. Many hormones are reduced to suboptimal levels. Normal negative feedback loops are inhibited and binding carrier hormones are disrupted.

Because of its intricate relatedness through the OAT axis, the thyroid affects the ovarian and adrenal systems. Reproductive gland activities are influenced by the thyroid through its effects on metabolism.

The effects of the thyroid hormones on the production of progesterone, in particular, affect whether a woman becomes pregnant and sustains that pregnancy.

In its close relationship with the adrenals, the thyroid is affected by the down-regulation of body systems seen in advanced adrenal fatigue.

High levels of estrogen curtail the effects of thyroid hormones as well as the effectiveness of cortisol. These effects lead to hypothyroidism and added pressure on the adrenals. When the thyroid and adrenals are negatively affected by estrogen dominance, they increase the effects of estrogen dominance.

One of the signs and symptoms of a dysfunctional Hormone circuit is estrogen dominance. Some of the dangers of estrogen dominance include the increase of thyroid-binding proteins in the blood. This may lead to a state of subclinical hypothyroidism in which lab tests show normal results, but the levels of thyroid hormone in the blood are low. Severe cases of estrogen dominance can lead to secondary hypothyroidism. High levels of estrogen inhibit the adrenal cortex in its responses to signals from the brain. This means the brain may be signaling for increased cortisol production, but the high estrogen levels blunt the response from the adrenals.

The development of breast cysts is another indicator of a dysfunctional Hormone circuit. Once again, estrogen plays a major role in the development of these cysts. The excess estrogen may be due to normal aging or to continuing and chronic stress.

The development of cancer in the breasts, ovaries, or uterus may be another sign of a dysfunctional Hormone circuit. Estrogen is the culprit in many of these cancers. Excess estrogen prompts the growth and proliferation of breast cells that may then turn cancerous.

Estrogen deficiency can also be a sign of a dysfunctional Hormone circuit. Much of the time, this condition comes with the natural process of losing estrogen as women age. The larger problem that comes with estrogen deficiency is the loss of the neuroprotective function of estrogen. This increases the risk of stroke and/or of developing serious dementias such as Alzheimer’s.

The development of fibroids is another indication of a dysfunctional Hormone circuit. These cause a multitude of physical problems including pain, heavy menstrual flow, and prolonged menstrual flow. While their cause is unclear, estrogen dominance is typically present.

Infertility is often encountered as a result of a dysfunctional Hormone circuit. The lack of female hormones to produce a fertile egg and to sustain a pregnancy are often the culprits. These hormone levels are low due to an increase in stress that leads to adrenal fatigue.

Low libido as an indicator of a dysfunctional Hormone circuit comes as a result of it not being essential to the survival of the individual. When the body is stressed to the point of adrenal fatigue, it goes into an energy conserving mode and shuts down these non-essential body systems.

Menopausal metabolic syndrome occurs in most women as they enter menopause. It may also be an indicator of dysfunctional Hormone circuit. The imbalance in hormones available to women at this time of life becomes more significant if the Hormone circuit is dysfunctional.

Polycystic Ovarian Syndrome or PCOS can develop when the normal menstrual cycle of a woman is disrupted by anovulation. The follicles that fail to release eggs can then develop into the multiple cysts that mark the condition. A relative dominance of estrogen and androgens versus progesterone is a root cause of PCOS.

A lack of energy called a PM slump often occurs with a dysfunctional Hormone circuit. Typically, it occurs around 3 p.m. and requires a nap with some kind of snack to build up the energy level once more. This condition may be due to a low level of cortisol when adrenal fatigue is present.

PMS, premenstrual syndrome, is related to estrogen dominance as are so many of the indicators of dysfunctional Hormone circuit.

When the adrenals are stressed to the point of being unable to produce sufficient cortisol to fight stress effects, fatigue is one of the results. This is an indicator of a dysfunctional Hormone circuit.


Dr. Lam’s Key Question

As women age, relative levels of estrogen increase over progesterone, leading to estrogen dominance and Hormone circuit imbalance. Much more progesterone is required than estrogen, so even a smaller ratio can cause imbalance. After menopause, some women can suffer from estrogen deficiency.