How Hormones Can Help Address What Causes Fatigue

By: Michael Lam, MD, MPH; Dorine Lam, RDN, MS, MPH

Hormone replacement therapy can be a consideration in What Causes FatigueAdrenal hormones are essential for life. Too much of them or too little, however, can be dangerous. An imbalance of these crucial hormones can oftentimes also be the source of what causes fatigue. Hormone replacement is commonly prescribed by physicians when presented with a patient’s symptoms suggestive of adrenal insufficiency. In the early days of adrenal hormone replacement, researchers had little clue of the proper dosage or the complications resulting from toxicity. Misled by improvement in their patients’ symptoms, they gave patients many times more adrenal hormones than the normal amount. Cortisol was the drug of choice. Many patients suffered toxic effects as a result of this and died. Long term and excessive use of cortisol has many negative side effects as well, to the extent that its use as a performance enhancer in competitive sports has now been universally banned. As a result of these bad experiences, many researchers became frightened and avoided prescribing adrenal hormones such as cortisol whenever possible.

In addition to adrenal hormones, the use of thyroid replacement to overcome fatigue brought on by Adrenal Fatigue is a common practice. In fact, many people with Adrenal Fatigue with symptoms of low thyroid function are prescribed thyroid medications as if they suffer from primary hypothyroidism. Many continue to suffer. In the early days of thyroid hormone replacement, patients received up to many times the usual dose of thyroid hormone as well and as a result, the toxic effects could be severe.

Clearly, hormone replacement therapy in a setting of Adrenal Fatigue requires careful attention and the use of adrenal hormones needs to be put into perspective. In the right situation and using the right dose, hormone replacement can be of great benefit alleviating what causes fatigue.

Medical science is just beginning to realize that a person can feel horrible and function poorly even with a minimal to moderate hormone deficiency that is not clinically detectable by routine blood tests. This is evident in the case of Adrenal Fatigue. Adrenal hormones are under the control of the hypothalamus-pituitary-adrenal axis where over 50 hormones are involved, and dysregulation of any one can produce unpleasant symptoms. For example, low aldosterone level can lead to blood pressure irregularities and fatigue, high estrogen can trigger PMS and anxiety, and low cortisol output can lead to sugar dysregulation, hypoglycemia and sluggishness. Those in the advanced stages of Adrenal Fatigue are especially vulnerable. Unfortunately, laboratory tests and other investigative tools are not very helpful when it comes to Adrenal Fatigue due to inconsistent clinical correlation. However, good qualitative challenges can be helpful. Paying close attention to the signs and symptoms of Adrenal Fatigue is perhaps the most effective way to assess whether or not there is the need for hormone replacement. The ultimate decision as to whether or not to use hormone replacement as an Adrenal Fatigue recovery tool is best left to the professional. Due to poorly understood patho-physiological mechanisms, some trial and error in administering hormone replacement will be inevitable even in the best of hands.

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What Causes Fatigue? – Adrenal Glands 101

The adrenal glands are two small glands; each about the size of a large grape and their role in producing hormones required for optimal living is crucial. The outer adrenal cortex comprises eighty percent of the adrenal gland and is responsible for producing over 50 different types of hormones in three major classes-glucocorticoids, mineral corticoids and androgens. Without proper hormonal production and balance, it is impossible for anyone to feel good.

When the adrenals are weak, production of any or all of these hormones will be affected. Hormones can be over-produced or under produced, depending on the state of fatigue of the adrenals, and also on each person’s intrinsic body constitution. For example, cortisol output in the body usually rises in Stages 1 and 2 but will subsequently fall when a person enters into Stage 3 and beyond. DHEA level tends to fall gradually as Adrenal Fatigue progresses from Stages 1 to 4. DHEA output can also be high temporarily during onset of Adrenal Fatigue. Pregnenolone output also tends to rise in early stages of Adrenal Fatigue just like cortisol before it starts to fall due to a phenomenon known as pregnenolone steal.

You can check your hormone levels to see What Causes Fatigue


In addition to output considerations, we need to pay attention to how these hormones are broken down and metabolized. All steroidal hormones are metabolized to a great degree by the liver. The more advanced the Adrenal Fatigue, the more compromised the liver function generally. Hormones required for recovery from Adrenal Fatigue need to be considered not only their absolute quantity. Just as important is consideration of the overall clearance state of the body to get rid of metabolic byproducts of the various hormones. Hormone replacement therapy for people suffering from Adrenal Fatigue, whether it is in synthetic or bio-identical form, is therefore difficult and challenging. It should be undertaken only under the close supervision of an experienced health care provider after more gentle first line recovery tools have been exhausted. In other words, adrenal hormone replacement should not be considered as a first line remedy until better and gentler compounds that can get the job done without the risk of side effects, has failed. Premature use of adrenal hormonal replacement is common in most self-navigation programs, is a common mistake, and can be a major cause of recovery delay or failure. Improper use of adrenal hormonal replacement in fact can be what causes fatigue and makes the condition worse due to toxicity, paradoxical effects, addiction, and withdrawal complications. Worst of all, it may also trigger adrenal crashes.

Steroidal Hormone Synthesis Pathway

A steroid is a chemical substance with four carbon ring structures attached to each other in a very specific and unique fashion. Cortisol, DHEA, testosterone, pregnenolone, progesterone, and estrogen are all steroid-based hormones that chemically look very similar to each other in terms of their basic molecular structures. They are all made in the adrenals with cholesterol being the raw material. However, their actions differ markedly, with enormous differences in how they function and in the roles they play in the various chemical factories of our bodies.

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The following is a simplified diagram of how the key adrenal hormones are made:

To discover What Causes Fatigue, look at the adrenal pathway


Each hormone produced acts as part of an overall orchestra of hormones where proper balance is essential for optimal adrenal function. Each hormone has an important role to play in the overall scheme of things inside the body. In addition to recognizing the sequential cascade of hormonal synthesis, it is very important to understand that pro-hormones such as pregnenolone and DHEA, which are placed naturally at the top of the cascade, are gentler as compared to down-stream hormones such as testosterone and cortisol. The more gentle the hormone, the more nurturing it is for the adrenal to make its own down-stream hormone and the less will be the side effects. Pro-hormones are less potent but contrast this with the cortisol, which is the most potent, and has the greatest potential side effects.

This paper will examine some of the most common steroidal hormone replacements and their clinical ramification in the Adrenal Fatigue setting and these hormones are: Pregnenolone, DHEA, cortisol, melatonin, testosterone, estrogen, and progesterone. Thyroid replacement will be covered separately due to its importance.


Pregnenolone is called the mother of all steroid hormones for a good reason. It is a steroid hormone at the top of the hormonal production cascade. It is also the precursor in the synthesis of female hormones such as estrogen and progesterone, mineralocorticoids such as aldosterone that is responsible for sodium regulation, glucocorticoids such as cortisol that suppresses inflammation and helps to reduce stress, and androgens such as testosterone. Pregnenolone is therefore aptly called a pro-hormone.

Back in the 1940’s, when researchers started experimenting with the use of pregnenolone, they realized that it could be helpful for people who were under stress and that it could also increase energy in those who were fatigued. However, at about the same time, cortisol, another closely related hormone, was discovered and it stole the limelight, as it was far more potent. When cortisol was given to individuals with rheumatoid arthritis or other inflammatory conditions, there were outstanding short-term improvements.

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During periods of stress, the output of adrenal steroids such as cortisol will increase, which will put a great demand on pregnenolone production. This may lead to pregnenolone deficiency, which in turn may lead to reduction of both glucocorticosteroids and mineralocorticoids such as cortisol and aldosterone respectively.

Numerous studies have shown the effects of pregnenolone on the body and brain. In normal people, pregnenolone will boost energy, elevate mood and improve memory and mental performance. Pregnenolone will also create a sense of well being while improving the ability to tolerate stress. Furthermore, pregnenolone has a host of other benefits, which include the ability to influence cerebral function, the female reproductive cycle, immune defenses, inflammation, mood, skin health, sleep patterns, stress tolerance, and wound healing. As an anti-aging tool, taking pregnenolone will therefore rejuvenate the entire adrenal cascade. However, in the case of Adrenal Fatigue, replacement tends to be more complex.

Some with Adrenal Fatigue find pregnenolone replacement improves their energy, vision, memory, clarity of thinking, well being, and often sexual enjoyment or libido. Some women report lessening of hot flashes or premenstrual symptoms and this is likely due to the rise of progesterone (the biological daughter of pregnenolone) reduction in estrogen dominance. Others, however, may find pregnenolone worsen existing fatigue and may even trigger adrenal crashes. Such paradoxical reactions are common. The more advanced the adrenal weakness, the more likely such experiences are common.

Part of the reason can be explained by pregnenolone’s unusual response curve. Many studies have found a U-shaped distribution in the therapeutic response to pregnenolone therapy. The U-shaped distribution describes a benefit associated with low dose pregnenolone, a loss of effect with increasing dose of pregnenolone, and a second peak of benefit with higher doses of the steroid. It is unknown what dosage range is represented in either part of the U-shaped curve for humans and whether or not this curve is altered by disease.

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The cells of the adrenal glands, as well as the central nervous system, synthesize pregnenolone. In Adrenal Fatigue, pregnenolone level usually stays high in early stages, but tends to be low as adrenal weakness progresses due to a phenomena known as “pregnenolone steal” as the pregnenolone level drops because the body bypasses pregnenolone production in favor of producing more down-stream hormones such as DHEA and cortisol.

Taking pregnenolone for adrenal fatigue can therefore be challenging for multiple reasons as paradoxical reaction is a major concern. In addition, one can take what appears to be an adequate dosage but will not benefit from this if the body is shunting it towards cortisol production. On the other hand, overdose is possible if too much is taken over time.

The normal starting dose is 15 mg, increasing up to 100 mg for men or women. Pregnenolone should be derived from a pharmacologically pure product and not a yam-derived “precursor.” Oral pregnenolone pills work well. Sublingual administration is an excellent option by bypassing the initial liver metabolism that occurs after swallowing an oral pill but it tends to be “spiky” and not well tolerated by those who are sensitive or in advanced s adrenal fatigue state.

Pregnenolone is converted in the body to progesterone and these two hormones have some overlapping similarities. Pregnenolone is also converted into DHEA, which, in turn may convert into androstenedione, testosterone, and estrogens. Pregnenolone supplementation may increase progesterone levels and consequently other hormones in the body (testosterone and estradiol).

Side effects include:

  • Over stimulation and insomnia – low doses can be helpful for sleep when taken in the morning. This is especially prominent in those with advanced adrenal fatigue.
  • Irritability, anger or anxiety – low doses can actually ease a person into a relaxed feeling, while higher amounts may lead to irritability. The exact reason for this is not known.
  • Acne can occur due to the probable conversion of this hormone into androgens.
  • Headaches are possible with high dosages – possible scalp hair loss if used daily for prolonged periods. Pregnenolone converts into DHEA, which in turn converts into testosterone and possibly onto DHT. Pregnenolone can also be converted into progesterone.
  • Irregular heart rhythm, heart palpitations, even when the dose is as low as 10 mg. This side effect can be serious in the elderly or in those with heart rhythm disturbances.
  • Pregnenolone may cause disturbances in the endocrine system, including changes in the menstrual cycle and problems associated with hormone sensitive diseases, or it may interact with hormone therapy such as oral contraceptives.
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Due to the possible side effects, pregnenolone should be taken under the supervision of a health care professional. Do not rely on blood or saliva tests alone to determine how much pregnenolone should be taken as the clinical correlation is unreliable in Adrenal Fatigue.

Due to its antagonistic effects on the GABA receptor in the central nervous system, pregnenolone therapy may be contraindicated in some people with a history of seizures. Pregnenolone may inhibit drugs used to increase GABA activity (i.e. Neurontin); these drugs are frequently used in the treatment of epilepsy and depression.

Both pregnenolone and DHEA can be taken together for adrenal fatigue. Since some pregnenolone is converted into DHEA, the intake amount of DHEA can be lowered if both are taken together.

DHEA (Dehydroepiandrosterone)

DHEA is the biological daughter of pregnenolone. It is a weak androgenic hormone made in large amounts in the adrenal glands of both sexes. DHEA is a precursor of testosterone, estrogen, and corticosteroids. Their actions are similar, but generally, DHEA is more potent than pregnenolone. Energy generation appears to be more intense.

DHEA is commonly used as a hormone replacement therapy for energy enhancement and anti-aging. Supplementation with DHEA can improve well-being, energy levels, moods, and libido for normal healthy people. Dosages of 15 to 25 mg of pregnenolone and 25 to 50 mg DHEA seem to do the trick in many women as it can bring them a renewed sense of well-being. Men are less hormone sensitive and the results may not be as evident. For men, direct testosterone precursors such as androstenedione (and its metabolite androstenediol) may be more effective. These protocols, however, only apply to healthy individuals and not to those who are afflicted with Adrenal Fatigue.

DHEA is also widely used in Adrenal Fatigue. Their actions tend to mimic pregnenolone, but amplified, both in terms of desired results and side effects. Therefore, DHEA use should be judicious, as different doses appear to do different things. DHEA does not convert into progesterone; rather it converts into estrogen and testosterone. High dosages (100 to 200 mg or more) can lead to a repartitioning of body mass as a result of the conversion of the DHEA into more androgenic steroid hormones. Significant side effects are similar to those of pregnenolone, only more severe. Hair loss and acne are particularly common.

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Even low dose DHEA can be problematic, as it tends to be quite stimulatory for those people with advanced adrenal weakness. In particular, those in Stage 3 (Adrenal Exhaustion) tend to react strongly even at minute dosage. Additional side effects such as severe anxiety, feeling jittery, and PMS are common and they seem to be more prevalent in women.

Since DHEA is a slight mood elevator, it can potentially clash with anti-depressants. Theoretically, the dosage of anti-depressants can be lowered if DHEA is taken. People on cholesterol lowering drugs as well as blood thinning medications, such as Coumadin, may need to watch their medications, as well as their requirements, because the amounts required to be taken may well be reduced since DHEA has both a cholesterol lowering and blood thinning effect. Studies have shown that DHEA also reduces appetite and this means that those who want to lose weight may benefit from DHEA, and those who are already on weight reduction pills may need less.

One interesting thing about DHEA is that it is not regulated by a negative feedback loop in the body. In other words, taking DHEA supplements will not suppress the production of these hormones or cause the adrenals to rest and result in atrophy from disuse. Theoretically, no “resting period” is required, although it may be a good practice to have a resting cycle of a few weeks for every few months of therapy.

Commercial DHEA products are made from diosgenin, an extract from the Mexican wild yam of the Dioscorea family. Biochemists can convert diosgenin to DHEA by engineering a series of chemical conversions, but such conversion will only happen in the laboratory and not in the human body. Therefore, ingestion of Dioscorea plant extracts cannot possibly lead to the formation of DHEA inside the body. DHEA should be used under professional guidance in the Adrenal Fatigue setting. Dosage determination can be tricky as it is not straightforward. Special attention needs to be paid to the many possible side effects similar to those of pregnenolone.

Depending on the stage of Adrenal Fatigue and on each person’s constitution, the blood or saliva DHEA level can increase while Adrenal Fatigue is in progression instead of going into gradual decline. Serum absolute levels are generally not very helpful due to inconsistent clinical correlation. From the Adrenal Fatigue perspective, DHEA should be viewed in conjunction with total cortisol. DHEA is an anabolic hormone (a building up hormone) while cortisol is a catabolic hormone (for breaking down tissues). The absolute DHEA level by itself in the Adrenal Fatigue context has little meaning. If the total cortisol to DHEA ratio is high, then there will be excessive cortisol relative to DHEA. That points to a body in a catabolic state.

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The most important anti-stress hormone in the body is cortisol and it is produced in the adrenal cortex. Cortisol protects the body from excessive Adrenal Fatigue by:

  • Normalizing blood sugar level Cortisol increases the blood sugar level in the body, thus providing the energy needed by the body to physically escape the threat of injury in order to survive. Cortisol works in tandem with insulin, which is released from the pancreas, to provide adequate glucose to the cells for energy. More energy from any source is required when the body is under stress, and cortisol is the hormone that makes this happens. In Adrenal Fatigue, more cortisol is secreted during the early stages but in the later stages of Adrenal Fatigue (when the adrenal glands become exhausted), cortisol output is reduced.
  • Anti-inflammation Response Cortisol is a powerful anti-inflammatory agent. When we have a minor injury or a muscle strain, our body’s inflammatory cascade is initiated, leading to swelling and redness commonly seen when an ankle is sprained or when there is an insect bite. Cortisol is secreted by the body as part of its anti-inflammatory response and its objective is to remove and prevent swelling and redness in nearly all tissues. These anti-inflammatory responses will prevent mosquito bites from getting bigger, bronchial stress, and eyes from swelling shut due to allergies and Adrenal Fatigue.
  • Immune System Suppression People with high cortisol levels are very much weaker from the immunological point of view. Cortisol influences most cells that participate in the body’s immune reaction, especially white blood cells. In particular, cortisol suppresses white blood cells, natural killer cells, monocytes, macrophages, and mast cells. Finally, cortisol also suppresses Adrenal Fatigue.
  • Vaso-constriction Cortisol contracts mid-size arteries. People with low cortisol levels (as in advanced stages of Adrenal Fatigue) have low blood pressure and reduced reactivity to other body agents that will constrict blood vessels. Cortisol tends to increase blood pressure that is moderated.
  • Physiology of Stress People with Adrenal Fatigue cannot tolerate stress and will then succumb when faced with severe stress. As the stress level increases, progressively higher levels of cortisol will be required by the body. When the cortisol level cannot rise in response to stress, it is impossible to maintain the body in its optimum stress response condition and in this respect, we can conclude that stress does kill.
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In short, cortisol sustains life via two opposite, but related, kinds of regulatory actions: releasing and activating the existing defense mechanisms of the body, while shutting down and modifying the same mechanisms to prevent them.

Cortisol production from the adrenal glands is controlled via the hypothalamus-pituitary-adrenal (HPA) axis. There is an existing negative feedback loop that governs the amount of adrenal hormones that are being secreted under normal circumstances in normal people. For example, the HPA axis adjusts cortisol levels according to the body’s need via a hormone called Adrenal Corticotropic Hormone (ACTH) that is secreted by the pituitary gland in response to signals from the hypothalamus. When the ACTH binds to the walls of the adrenal gland cells, a chain reaction occurs within the cells, leading to the release of cholesterol where it is manufactured into pregnenolone, the first hormone in the adrenal cascade. After this, cortisol is released into the blood stream where it travels in the circulatory system to all parts of the body and back to the hypothalamus.

Cortisol and ACTH are not secreted uniformly throughout the day. They follow a diurnal pattern, with the highest level secreted at around 8:00 a.m., after which there is a gradual decline throughout the day. Episodic spikes during the day can also occur when the body is stressed or when certain foods are eaten. The cortisol level is at its lowest between midnight and 4:00 a.m. Morning cortisol is indicative of peak cortisol output. Noon cortisol is indicative of cortisol adaptability and usage. Afternoon cortisol is associated more with sugar regulation than adrenal cortex function, while evening cortisol level points to adrenal baseline function.

Cortisol levels can show What Causes Fatigue


Cortisol level, especially in the morning, is characteristically high for those in Stages 1 and 2 Adrenal Fatigue as the adrenals are put on overdrive to produce more cortisol in order to neutralize stress. As Adrenal Fatigue progresses, cortisol output will eventually peak and then start to decline. Those people who are in Stage 3 Adrenal Fatigue invariably face a low cortisol level in the morning. After this time, the body’s cortisol output for the rest of the day will remain low. A 24-hour saliva cortisol curve is commonly flat throughout the day in Adrenal Exhaustion (Stage 3 Adrenal Fatigue). There are many exceptions to the above generalization and this is why relying on a test result to determine the body’s cortisol level, as the sole clinical yardstick can be very misleading. For example, some patients who are Stage 2 Adrenal Fatigue can present themselves with high evening cortisol but low or normal morning cortisol. These people tend to have low energy in the morning, with alertness returning around evening time. Despite high evening cortisol, they may be able to sleep well without sleep onset insomnia that commonly plagues those with high evening cortisol. As if this is not confusing enough, some people in Stage 3 Adrenal Fatigue clinically can present with a typical Stage 1 Adrenal Fatigue cortisol curve for reasons not well understood.

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Conventional physicians have been using cortisol, also known as hydrocortisone, to combat Addison’s disease for decades. The drug is widely available under the trade name Cortef. Some have advocated the use of cortisol for treating Adrenal Fatigue as well. Some physicians, notably, Dr. Jefferies in the mid 1980s, have advocated low dose cortisol as safe for long-term use. Dr. Jefferies found that as long as the adrenal hormone level is kept within the normal range, the main toxicity that a patient might experience was a slight upset stomach, due to the body not being used to having the hormone come in through the stomach. Advances in nutritional therapeutics over the years have now greatly reduced the need of using this medication in most Adrenal Fatigue situations other than in the most serious cases. Many, however, continue to use cortisol as a first line recovery medication for Adrenal Fatigue. Over-use of cortisol as an Adrenal Fatigue recovery tool is a serious concern.

There is little questionof the great benefits of cortisol for those who need it; cortisol can be a lifesaver for someone in a severe stage of Adrenal Fatigue. The gentler natural compounds such as vitamin C, vitamin B, DHEA, and pregnenolone, when dosed and delivered properly, will greatly support adrenal health. In such cases, external cortisol administration may be delayed or avoided. However, the clinical picture is anything but straight-forward.

The use of cortisol must be considered with great care. This is because the more advanced the Adrenal Fatigue the more prevalent the symptoms of intolerance. A good portion of people suffering from advanced Adrenal Fatigue actually cannot tolerate cortisol and in fact, their condition can become worse, even at low dose. Adrenal crashes may be triggered. The exact etiology is not known. Many will require a few weeks to get used to the medication, and the beneficial effect may not be immediately evident. Still worse is the issue of addiction and withdrawal symptoms, as anyone who has gone through those problems will tell you what a nightmare things can be.

Fortunately, as mentioned earlier, modern advances in nutritional therapeutics have rendered the use of cortisol unnecessary in most cases. Cortisol can be considered as a last resort. In fact, one of the key goals in Adrenal Fatigue recovery is to let the body heal itself naturally and wean off from cortisol dependency for those who have been on it long term.

Most patients find that 5 to 10 mg of Cortef in the morning, 0 to 7 1/2 mg at noon and 0 to 2 1/2 mg at 4 p.m. often work best. The actual dosage used needs to be adjusted to match the body’s need. Those who are on cortisol should slowly decrease their dosage after a few months if possible, eventually discontinuing the treatment entirely. The key to this is to rebuild the adrenal reserve first with natural compounds before titrating down cortisol dosage to avoid negative and unpleasant rebound withdrawal side effects and adrenal crashes.

There are many side effects when using cortisol. If the dose is too high, one may feel shaky and the dosage should then be lowered. If cortisol causes upset stomach, the patients should take it with meals or lower the dose. If taken too late in the day, Cortef can disrupt sleep. At a dose of over 20 mg a day, one will begin to see the more toxic side effects of cortisol. Clearly higher doses are not recommended unless the benefits do clearly outweigh the risks.

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Another important function of the adrenal glands is to maintain blood volume and pressure. Low blood pressure, low blood volume, electrolyte imbalance, and dehydration are common in people suffering from Adrenal Fatigue Stage 3. In such cases, the prescription adrenal hormone, fludrocortisones (sold under the brand name Florinef) may be indicated and can be a lifesaver.

Read Part 2 Now!

© Copyright 2012 Michael Lam, M.D. All Rights Reserved.

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  • Robert says:

    Just wanted to thank you as well for putting together this information. I have found the subject of adrenal hormones so confusing, and a lot of websites do a poor job of explaining it. Finally, a site that cuts through it all in a straightforward way!

    In the past year I have taken high dose prednisone (50mg and 60mg) on two occasions, spanning several months. I was then able to titrate down and eventually stop. However, this year I find I am caught in the cycle of adrenal recovery where my original health condition is susceptible to flaring. I have Inflammatory Bowel Disease and prednisone helps control it until the gut lining can heal. But this year I’m finding the lack of adrenal strength is allowing the gut inflammation to creep back in — perhaps a cortisol deficiency? Also have low BP, electrolyte and blood volume issues, etc. So I’m caught in a catch-22 where I need cortisol to control inflammation but might not have enough and they want to put me back on prednisone.

    I just finished my prednisone taper a month ago so it’s too soon for an official adrenal fatigue diagnosis. They may recover. I just don’t know what to do in the mean time to support them. My doctors here are useless, they aren’t willing to do adequate investigation, even simple blood testing. Seeing an endocrinologist will take 5 months.

    I experimented with DHEA at 25mg/day, but I found it too strong. I do feel that my testosterone levels are currently decreased, so my entire adrenal cascade is weak or imbalanced. But the DHEA did not seem to solve the problems I’m describing, it just made made libido higher and made me more irritable, but it didn’t seem to quench inflammatory problems (which are admittedly complicated, but there is definitely an adrenal relationship).

    The other thing I’m not clear on is if taking adrenal pro-hormones and other nourishment aspects can undo adrenal atrophy, or if it’s basically just damage control and maintenance? I’m 30 and it would be sad to find out that prednisone has destroyed my adrenals. My MD has said that reduced adrenal function is “forever”, but they say that about everything.

    I may look into trying pregnenolone at low doses as a supportive measure. I know I should be doing it under a doctor’s advice but I don’t have medical resources right now to help me with fine tuning, and I’m kind of desperate.

    Thank you!

    • Dr.Lam says:

      Prednisone is a drug of almost last resort, and repeated use can lead to withdrawal, resistence, and tolerance. I can sense your plight and your effort to titrate using pro-hormones. You do have to be careful as they may not be indicated. Click Adrenal Fatigue & Hormone Therapy for more information.

      Dr Lam

  • Helen P. says:

    I just wanted to stop by and thank you for your time and this website 🙂 only takes 1minute of my day to thank you for the millions of minutes you dedicated to this so I suggest others do the same

  • Stephanie says:

    Thank you for the information, i have been suffering with symptoms for a while and through reading this i now how a better understanding of what i am going through. Wasn’t aware how much hormones were so closely correlated with fatigue.

  • Savannah Jane says:

    I love the fact I can get lost on this site and not feel guilty about it. I feel like I have used my time to benefit my life tenfold by gaining the knowledge shared with each article. I can’t thank you Dr Lam enough for your knowledge

    • Dr.Lam says:

      thanks for your kind words. The more you know, the better for you to navigate through this condition.

      Dr Lam

  • Elena says:

    Can you provide more information about the use of DHEA/Pregnenolone when you have uterine fibroids? I’m reading mix reviews about it. I know uterine fibroids can cause nausea but after being on DHEA and pregnenolone (for stage 3 AFS) for a month my nausea has worsen.

  • Eva Corral says:


    I have battled fatigue my entire life, insomnia, muscle spasms, back and hip pain; diagnosed with Fibromyalgia. Had a partial hysterectomy 5 yrs ago (ovaries and cervix intact. I’ve recently came across an article on on Adreal Fatigue and ordered a saliva test. My results came in yesterday and before running to different doctors I would like your advice on what questions to ask. I have an appt with an naturopathic/accupuncture/ Md next week. I am so confused with all the content found online….
    Test taken: 06/15/2016
    Results: 24 hour saliva test
    Estradiol 0.7
    Progesterone 127
    Ratio Pg/E2 181
    Testosterone 14
    DHEAs 2.6
    Morning 3.5
    Noon 5.1
    Evening 1.9
    Night 0.8

    I would appreciate any and all advice.

    Thank you,


    Medications taken: ambien 5mg, 3 Benadryl each night. I No longer take anti depressants, lyrica anti inflammatory etc prescribed for fibromyalgia…too many side affects.

    • Dr.Lam says:

      Proper interpretation of lab must include close correlation with clinical situation. Wrong intepretation can be common. Click Laboratory Testing for more information. The same results can have different meaning depending on the history and current condition. Be very careful not to overread into the lab as it is easy to treat numbers while underlying root issue get worse.

      Dr Lam

  • Nicole says:

    Thank you for giving us the opportunity to understand all this valuable info. I’ve been dealing with Adrenal symptoms so long and I’m so happy that I have finally have a resource to look to.

  • stephanie allen says:

    Thank you for these articles. I have been in a severe adrenal crises for about a year. I went to a naturopathic doctor which helped a lot, but everyday is still a challenge and I feel worse in some ways, and very congested. All activities except for work have ceased. Where can I get a consultation to go on a full recovery plan?

    • Dr.Lam says:

      Some roller coaster type ride is part of the recovery process, but the overall trend should be up, and most people do better in a matter of weeks or months. Congestion points to underlying unresolved issues that can deter the recovery process. We have a telephone coaching service which deals with retarded recovery. You can call for an initial telephone appointment at no charge if you are in the US or Canada.

      Dr Lam

  • Amaya says:

    Dr. Lam – I was diagnosed with autoimmune thyroiditis three years ago and ever since I have been on T3/T4 medication and taking 100mg Pregnenolone daily to support adrenals. I have been feeling WONDERFUL during three years with the thyroid medication and the Pregnenolone however:
    my periods stopped half a year ago and my gynaecologist prescribed a bi-gest cream containing Oestradiol and Progesterone to treat menopausal symptoms. A month after I started the cream, my hair started falling out in clumps, it is very severe hairloss. I am told the cream is supposed to have the opposite effect, allegedly Progesterone blocks DHT conversion… Could it be that it is not the cream but the Pregnenolone causing the hairloss (prolonged use?), or an interaction between the cream and the Pregnenolone? Could the addition of Progesterone to Pregnenolone have caused an excess of androgens in some way? The hairloss is dramatic, so I have stopped both the cream and the Pregnenolone. I would welcome insight into this. What is the mechanism by which Pregnenolone is linked to hairloss, is it the possibility of it converting into DHT?

    • Dr.Lam says:

      The DHT pathway is just one of many pathways that regulate hair health. When the adrenals are weak, we do see this type of clinical picture that you referred to . The exact mechanism is not known, but we suspect it is due to the dysregulation trigger by selected hormones that lead to paradoxical behavior. Fortunately, this can be stopped as far as reamining hair, but it usually takes some time to first resolve the underlying issue and rebuilt the system with proper balance and the hair loss slows. Remember that if you have unattended AFS underlying, the thryoid and pregnenolone may have made you feel great at first, but the price you pay is the masking the root problem, and the bio identical hormone can act as a negative trigger.

  • Leyla Salvo says:

    Dr. Lam- I was diagnosed four years ago with hypothyroidism with symptoms being heavy menses with resulting anemia/fatigue and constipation. I was placed on levothyroxine 25 mcg and my hair started falling out horribly. Two pregnancies ensued and all hairloss stopped three months into the pregnancies and again four months post partum..levothyroxine never fixed my initial symptoms and adding t3 did resolve constipation and heavy menses but the hairloss is still excessive and I am more exhausted than I should be..especially after a long day.

    • Dr.Lam says:

      When thyroid support fail to give you the solution, you have to start looking outside the box. Low thyroid function that is persistent can indicate adrenal issues and resistance issues. Hair loss is quite typical . Until these root issues are resolved, often more thyroid support only is temporary at best and many become overstimulated and “wired and tired” is possible. Hormones such as thryoid therefore can be helpful shortterm but you have to be alert when it fails. Click Adrenal Fatigue & Hormone Therapy for more information.

      Dr Lam

  • Neil says:

    Would taking pregnenolone decrease the body’s natural production of pregnenelone?

  • Mark says:

    Thank you, Dr. Lam, for making your research public. It has greatly contributed to my understanding of my unique situation (loss of ACTH from radiological damage to pituitary).
    My symptoms are therefore similar, but not identical to those from Adrenal Fatigue. I suffer from early morning adrenal crashes (even with a maintenance level cortef), and have an acute intolerance to sharp temperature drops. Any suggestions?

    • Dr.Lam says:

      Your situation is complex. Morning cortisol can be adjusted by titrating your meds according to your doc. If that does not work, then you have to start thinking outside the box. There are various other pathways that may be involved that may be deterring the normal function, including resistance that tend to be associated with people on long term steroid use. Sharp temperature drop intolerance is very significant as it points to underlying metabolic dysregulation and loss of proper regulation which is usually autonomically driven. This goes along with the resistance picture as one possibility. A detailed history will tell the big picture. Laboratory test are not very good and can even be misleading

      Dr Lam

  • Holly says:

    I read that in another Dr. Site that the body cannot convert Pregnenalone supplement into other hormones. Are there studies to demonstrate either way?

  • Sarah Z says:

    Dr Lam,
    I have been to several doctors, none of whom have any idea how to help me. Most of my blood work is “in normal range.” Hormonal saliva testing came back with extremely low cortisol levels (my evening level was 0.48 nmol/L) but my DHEA levels are sky high, causing high testosterone and estrogen dominance. My hair falls out all day long, even my eyelashes are falling out. I am so tired I’m afraid that I will lose my job, and I’m not even thirty yet. I can’t find anything online about high DHEA levels combined with low cortisol. I also take a lot of sublingual vitamin b, but have no energy. It’s like my body cannot utilize the hormones and nutrition that are available. Have you ever seen anyone with the high DHEA/low cortisol paradox? If so, what helped them?

    • Dr.Lam says:

      A high or low DHEA has little relevance to the cortisol clinically because of various mechanism in place in addition to the straight physiological pathways which does not apply to everyone. Nothing unusual. We deal with this in our telephone coaching program frequently. Loss of hair is often in a case like this trigger by AFS resulting in loss of protective conversion from testosterone to DHT in non AFS people , resulting in more DHT and thus hair loss. The exact reason is unknown but the good news is that this often resolve itself when adrenals improve. Excessive Vitmain B is not reocmmended as it will only make things worse over time. Your situation cannot be resolved by someone who tries to “go by the book” because the book does not recognize AFS and thus miss the many connection when AFS is in place. Only a detailed history can put the puzzle together. The more lab you , the more likely you are going to be more confused. The more you stimulate the adrenal including with Vitamin B , herbs and glandulars, the worse it gets. However, if you are already on these, you should not stop abruptly or without an alternative safety net in place that is right for you as you risk withdrawal and crashes. We take great care in crafting a program for people like you to avoid the many issues you bought up.

      Dr Lam

  • Emma S says:

    Dear Dr.Lam,
    i have read your site with much interest, such information proving a rare find on the internet. I had an ASI done several months ago, the results showing extremely low levels of DHEA and cortisol peaking slightly in the morning, though not as high as it should be. Brief medical history – type 1 diabetes for 21yrs, double transplant (kidney/pancreas) in 2003, prednisolone treatment for 3yrs finishing 3yrs ago. Prior to taking the ASI was experiencing hypoglycaemia, fatigue, intolerance to stress, symptoms of hypothyroidism,etc. I have been taking a Nutri supplement (adrenal glandular) and have also addressed my diet, removing all sugars and any possible gut inflammatory triggers. The results, I feel a lot better, no more low blood sugars, mood is more level, energy levels increased. However, I know there is still a way to go, I am still experiencing symptoms of low thyroid, there is still an intolerance to stress, and so my question is, will pregnenolone and/or DHEA supplementation benefit me? I would greatly appreciate any guidance, many thanks.

    • Dr.Lam says:

      Your situation is quite complex because of your history. low thyroid function often goes with low adrenal. The use of hormones and glandular of any king needs to be carefully evaluated because it can often mask the underlying problem, giving you a false sense of improvement and only lead to dependency and withdrawal issues. On top of that many hormones do normalize itself and external hormones can potentially lead to dysregulation of feedback loops. you need to talk to your doctor prior to embarking on such a program. They do have their place under proper situation. Click Adrenal Fatigue & Hormone Therapy for more information. Also click Adrenal Fatigue Glandular & Herbal Therapy for more information.

      Dr Lam

  • Heather Bradley says:

    Dear Dr Lam

    I recently discpvered your website and it’s FAB!

    What a pity you don’t work in Britain. Do you have any pals from Med School working in Britain who are as intelligent about adrenals as you? If so, please give me their practice details.

    You see I’ve been going through the Menopause from Hell for 8 years now, yes, that’s right EIGHT years! Also, I’ve got ME or Chronic Fatigue as it’s also called. And since puberty I’ve had hypoglycaemia and oh, if that’s all not fabtastic enough… I’ve also had Adrenal Exhaustion (cortisol saliva tests proven) too, since 2003 (caused by severe financial stress) and so in 2009 when I was second year into the menopause a bomb basically went off in my body, which meant that what causes palpitations in a woman somehow has also caused me to experience INCREDIBLE, OFF THE SCALE hunger when under stress.

    Anyhow, so I’ve taken Isocort, Adrenal Glandulars, vitamins, maca herb – you name it I’ve tried it. Oh, and what I forgot to tell you is that I’ve spent 90% of the last 8 years in bed with the most profound and disabling exhaustion known to man. And woman!

    Because of the reduction in the oestrogen on my brain and as the brain in the control of the body, whenever I need to use my brain… such as typing this, talking, listening and reading… I tend to find that I get very,very hungery. Indeed, all stress makes me hungry.

    Since 2009 when the palpitaitons started I had to eat before I slept and then about 6 hours later I would get woken for food, with shocking palps. THen it would take me about 90 mins to 3 hours to get back to sleeps. And I forgot, my adrenals are my dominant hormone.

    Basically, my food isn’t working for me in the sense that I don’t get energy from food like I used to. I used to be so lovely and slim. Slim my entire life until (8.5 stone from 21 to 43) I got stressed and noticed getting fatter round tum but not eating any more food. With the AE and the Menopause and all the hunger of both… I have gone from 8 to 18 and its been a VERY painful time for me.

    I could not ignore the hunger before bed/in the night otherwise I would not get to sleep and if I did not get up in night I would wake next day and feel TERRIBLE and need to eat every 2 hours.

    It seems to me that m y food is not converting into energy properly, Is that one of the symptoms of AE, only I looked on your list and could not see that? It seems to me that my brain is tired because its not getting food properly. When I have to talk early in the morning (I am most awake in the evenings, naturally), if I eat something with sugar in it my brain does not feel SHATTERED and I do not feel hungry. But I don’t usually eat sugar. I tend to eat nuts in between my meals/protein.

    How I wish you practised in London. I would pay whatever you charged to come and see you and get better. I’m desperate!!

    I am thinking of trying a private doctor (I’ve taken supps and herbs for 5 years now but still not recovered) who can give me Plenadren (do you have that in USA), but I’ve just read one of your excellent articles on your website and it’s made me feel a bit worried about side effects of drugs.

    The menopause has been a MONSTER sized 24/7 stress on my body. Every day when I wake up I feel like there’s a 10″ slab of concrete pressing down on me. If you do prizes for endurance, resilience, fortitude and courage – I deserve one!

    How much is it to speak to yourself or one of your experts as all I want is to get better. Quickly. Or do you think that when my ovaries stop partying I wll naturally improve?

    Sorry this is so damn long Dr Lam but you are the only expert that I have been able to find.

    All I want is ENERGY, good sleeps, normal appetite and to be a size 10.

    THank you for reading this. I appreciate it. I’m also wondering if you have ever heard of other women suffering like I have/and still am?

    PS: American Docs are light years ahead of the Brits in many ways.
    When I had my first saliva/cortisol test (6.8 whole day, 2010) I got an apt with an endocrinoligst in Lancaster, a teaching hospital. He did a synacethen test and said everything was normal. I tried to tell him it wasn’t but he would not listen.

    I found out about saliva tests in a book written by an American Dr called, Feeling Fat, Fuzzy or Frazzled.


    • Dr.Lam says:

      your problem is quite typical of those that we handle. the body can often heal itself with the right tools. read my book if not already done so. call my office my staff will give you instructions on how to arrange a telephone appointment to see if you qualify for our telephone coaching program.

      Dr Lam

  • Anne W. says:

    How will I know when using Pregnenolone if my body is shunting it towards cortisol production? Also, I checked with two compounding pharmcies about Pregnenolone and they both use wild yam. Is this product still more beneficial than purchasing it over the counter?

    Thank you very much for your help.

    • Dr.Lam says:

      Your body automatically shunts when needed and is self regulated. you do not have control of that. As long as it is natural pregnenolone, they are the same. the difference is on dosage and route of delivery.

      Dr Lam

  • Amy M says:

    I tried for 10months to combat my stage 3-4 AF & hypothyroidism with the proper supplements and Cytomel, under a Integrative dr’s guidance but after a stressful event caused severe shakes, nausea, dizziness & weakness Hydrocortisone was finally necessary. Now I’m on HC & Florinef and dealing with major deficiencies in the following according to blood work: Pregnenoleone, DHEA, Progesterone, Testosterone & Iodine.
    I was put on DHEA & Progesterone, and have continued to suffer with DAILY HEADACHES, Irritability, Depression, weakness , terrible neck pain and fatigue I’m also Hypothyroid again.
    Why have I not made a full recovery with the help of Hydrocortisone?
    What are your thoughts regarding the use of Iodine when dealing with Adrenal Insufficiency? Any chance you can explain the headaches and why I haven’t improved more?

    • Dr.Lam says:

      Steriod is not necessary the solution. Not everyone can tolerate it, and in advance cases, they can actually trigger adrenal crashes. We see that in bodies that have already been overstimulated with other hormones such as thyroid, DHEA, etc. No surprise given your history. When you get to this stage, recovery is very challenging, but it can be done with proper guidance. Make sure you first find a doctor who knows what this is going on and not just keep increasing doses which can worsen the situation. We deal with many such cases in our telephone coaching service but the recovery process is slow and cannot be hurried but it can be done naturally.

      Dr Lam

  • Gerad says:

    I recently had a hair test which showed very high mercury levels and my doctor gave me an infusion of Dmps. Almost immediately I experienced a severe adrenal crash which has left me with arthritic type symptoms adrenal pain and fatigue. A naturopath has since put me on NAC, chlorophyll vitamin C, b5, however The NAC and chlorophyll appear to make me more fatigued. I tried hydrocortisone and pregnenelone briefly but found they made my condition more unstable although had some positives. I’m reluctant to use them and would rather recover in a more natural way if possible. Should I cease taking the NAC? How else can I lower the Mercury burden safely?

    • Dr.Lam says:

      What you experienced is common. Your body is weak already and the best intentioned approach of trying to help you by your doc actually backfired. You need to alert your doc that you have internal issues and your level of sensitivity so they dont put you on more well intentioned supplement that will only make you worse. When you body is this kind of fragile state, nothing will work well. You need to consider support the adrenals first. It is very delicate and no regular rules work because the system internally is not ready. You should not fight a battle until your body is ready. Mercury can be in the body for your lifetime and not cause problem. Just because you have high level does NOT mean that you have to aggressively get rid of it aggressively. Remember that until your adrenals are stable and strong, chances of you being successful with any program is very limited. The right thing done at the wrong time will hurt you more than help you. You should go back to your doctor and sit down and go over what happened and have a comprehensive plan before proceeding further with more potential damage coming. We take a long time to know the body, often weeks and months, and formulate a personalized plan to avoid the problem exactly what you have described and that is an important reason for our success.

      Dr Lam

  • Sonia says:

    Can pregnenolone supplementation cause the adrenals to shut down and atrophy or can pregnenolone supplementation take the load off the adrenals and help them to heal?

    • Dr.Lam says:

      The adrenal glands have a feedback loop where the signal to make more is turned off when there is sufficient. When you put external pregnenolone into the body over a long period of time and in high doses, such feedback loop may be involved. We have found that while in theory this pre-hormone seems to make sense for some, most people dont need it. Women, in particular ,should be careful due to hair loss and other issues. Read Adrenal Fatigue & Hormone Therapy for more information.

      Dr Lam

  • Rachel says:

    Hi Dr Lam. Thank you very much for the information, I’ve really enjoyed reading through your website and have found it extremely helpful. I just have a few questions. I recently completed a salivary adrenal test with the following results;
    Cortisol Morning: 6.0 nmol/L
    Cortisol Midday: 4.4 nmol/L
    Cortisol Afternoon: 3.5 nmol/L
    Cortisol Evening: 1.9 nmol/L
    Do these results suggest I am in stage 3 Adrenal Fatigue? My blood serum cortisol level, however, is very high.
    My other question is about DHEA. Both my DHEA results were high (DHEAS 33.8 nmol/L DHEAS/CORTISOL ratio 5.63). Do you know why that would be? It seems as though DHEA is often much lower with adrenal fatigue. I have Chronic Fatigue Syndrome also. Thanks very much.

    • Dr.Lam says:

      Dhea high can happen in early stages of AFS, and it generally goes lower as AFS advances. The cortisol curve needs to be correlated with clinical picture to make good sense. When you have CFS, the numbers can be very skewed . Try not to intepret the numbers on their as you can get very confused. Read Laboratory Testing for more information.

      Dr Lam

  • Kristy says:

    Hello Dr, THANK YOU soooo MUCH for offering us the opportunity to learn all these valuable info. I have had the Mirena IUD and I really felt that I had come back to life after so many years of suffering from extreme exhaustion and depression. Until then, I thought I had lost it and had become num and stupid. After I searched and found out about the dangers of synthetic hormones and got informed about the existence of the biohormons, I tried the cream (which by the way I find it to act like a very potent drug and that it dangerously boosts people’s ego and selfishness) and have also tried the pregnenelone and DHEA combination which led me into a terrible crash and heart arrythmias (low potassium) at the ER. I am 36, I feel that I haven’t really lived my life ever sinse I was a teen, and I am about to have the Intra- Uterus- Device placed once again, but I am afraid sinse the first time I had it removed, my immune system came down completely and I became seriously ill with infection and left with constant joint pain.some of my children are exhibiting signs of the same condition as I went through, while other members of my family are also struggling likewise. Please dear Dr, if you have any recommendations to give me, It would be greatly appreciated. Once again thank u so much…

    • Dr.Lam says:

      Your body is obviously very unique and anything you do should be done carefully with your doctor in full understanding. Do not be surprised with paradoxical and hypersensitivity type reactions based on the history you presented. I have a feeling something deep inside may be the root issue and that is not resolved, but I cannot do much more than alert you as this forum is for educational purposes only. you can call my office if you are at your wits end and I will talk to you and try to figure out what are the stones unturned so you can talk to your doctor further.

      Dr Lam

      Dr Lam

  • Bennet says:

    I go to bed at 9 by the latest every night, and get up at around 7 am, but no matter what I do, I don’t feel rested. Can you please point me in the right direction for understanding what’s going on?

    • Dr.Lam says:

      There are many reasons for waking up unrefreshed. they can range from structural problem like tongue obstructions, brain issues such as apnea, metabolic issue such as sugar imbalance, to adrenal issue such as having palpitations and waking up throughout the night. Each needs to be explored and investigated. Assuming that conventional medicine has nothing to offer, do look into adrenal fatigue as a possible cause of sleep issues. this article may help.

      Dr Lam.

      • Maggie says:


        Is it okay to take pregnenolone tablets during my menstrual cycle? How long does it usually take for low DHEA levels to normalize if i’m taking pregnenolone at 5mg to start?


        • Dr.Lam says:

          Pregnenolone is a powerful pro-hormone that can affact your menstrual cycle. you should seek your doctor’s advise prior to taking because everyone’s behavior can be different in the setting of AFS. If you have low DHEA, the first thing you should do is to find out why. In AFS, DHEA can be low and is part of the clinical picture. Trying to correct lab values without focusing on the underlying issue is a common recovery error. Do be careful. Click 7 Adrenal Fatigue Recovery Mistakes for more information.

          Dr Lam