Why should we be interested in hormones and hormonal substitution?


Hormones are the bodies messengers, they coordinate all vital repair, recovery and regeneration, without them we simply degenerate.


Hormones are intimately involved in every body function. Every cell has a receptor site for a hormone to communicate with the cell to turn it on, off, vary its rate, and coordinate repair. The amount of hormones are controlled by two master – glands glands in the brain- the hypothalamus and the pituitary.

Imbalance and lack leads to fatigue, sleep disturbance, sexual dysfunction, depression, impaired immune function, chronic illnesses, disease, "lack of thriving", degenerative state of decline, debility and earl death.

Imagine your health status in 10 years from now if you already today worry about persistent complaints and decline of energy. Many of us talk about lacking energy among other symptoms. Aging reduces the amount of hormones dramatically which leads eventually to collapsing of the entire organ network.


 Here is where energy medicine comes in. Energy medicine identifies and eliminates mental and physical toxic waste, and this jump starts your cell metabolism.

Part of that program includes hormonal therapy. Natural Hormonal Replacement Therapy (NHRT) with bioidentical hormones has become a mile stone in rejuvenating and anti-aging efforts.


A loss of hormonal balance, as occurs with aging, plays a predominant role in mental and emotional symptoms and in all illness. Restoration is ideally achieved through natural hormonal replacement therapy.



The decline in hormones with aging:


Pregnenolone 40% left with age of 70, growth hormone, testosterone, DHEA 50% decline from age 25 to 50, followed by a further 50% by the age of 75

Melatonin sharp, continual decline. Progesterone, an anti-cancer hormone, keeps estrogen in check. A lack through aging or stress leads to estrogen dominance and all kinds of illness.


24-hour saliva test from ZRT laboratory


This is a test kit that you can order directly from the lab yourself, or your doctor can provide you one which you then take home and complete. These home hormone saliva test kits have you collect a saliva sample in a small vial at 4 specific times of day (approximately 7 am, 11 am, 4pm and 11 pm).  After you have collected your 4 specimens, you mail the kit to the lab for analysis.  The test kit usually costs around $175., and includes the cost of analysis.


Pharmacy compounding is the art and science of preparing personalized medications for patients. Compounded medications are made based on a practitioners prescription in which individual ingredients are mixed together in the exact strength and dosage form required by the patient. This method allows the compounding pharmacist to work with the patient and the prescriber to customize a medication to meet the patient’s specific needs.



What are hormones?


A hormone (from Greek ρμή, "impetus") gives a signal to cells, telling them what to do. Produced by glands or nerve cells it is transported by the circulatory system or nerve cells to target distant organs. There, by logging on cellular surface receptors and other receptors it jump starts processes to regulate physiology and behavior. Hormones are the interface between nerves/glands and body.


Types of hormones:


There are 4 types of hormones: Amine, peptide, protein, and steroid hormones. Steroid hormones have a typical a four ring carbon structure and derive from cholesterol. We are foremost interested in steroid hormones since they are made by the adrenals, and easily depleted.


Hormones are structured like a key


Hormones are very specific. They match a specific receptor like a key to a lock. Their specific shape is achieved by their 3 dimensional steric space structure.


Steric effects arise from a fact that each atom within a molecule occupies a certain amount of space. If atoms are brought too close together, there is an associated cost in energy due to overlapping electron clouds (Pauli or Born repulsion), and this may affect the molecule's preferred shape (conformation) and reactivity.


There are two kinds of hormones:


First: Neuro-Hormones released by nerve cells transmitting signals from one neuron to  the next  (neurotransmitters) such as Glutamate, GABA, Serotonin, Dopamine, Adrenalin and Noradrenalin are both, hormones and neurotransmitters


Second: Endocrine hormones which are released into the blood stream by endocrine glands and targeting cells far away such as Melatonin, Human Growth Hormone, FSH, LH, Thyroxin, Parathyroid Hormone, Insulin, Adrenal hormones (steroids), sex hormones testosterone, estrogen, and progesterone





Glutamate - Glutamic Acid


The main activator of life functions is glutamate

Glutamate is an important neurotransmitter that plays the principal role in neural activation. Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. It is the precursor of GABA.

Monosodium glutamate (MSG) is a flavor enhancer commonly added to Chinese food, canned vegetables, soups and processed meats. The Food and Drug Administration (FDA) has classified MSG as a food ingredient that's "generally recognized as safe," but I think differently:

Some side effects:

  • Headache
  • Flushing
  • Sweating
  • Facial pressure or tightness
  • Numbness, tingling or burning in the face, neck and other areas
  • Rapid, fluttering heartbeats (heart palpitations)
  • Chest pain
  • Nausea
  • Weakness
  • Diarrhea immediately after food intake.

GABA: Gamma-Amino Butyric Acid

Gamma-Amino Butyric acid (GABA) controls glutamate by slowing it down and thus preventing over-stimulation. It is an amino acid which acts as a neurotransmitter in the central nervous system (CNS). It inhibits nerve transmission in the brain, calming nervous activity. As a supplement (250-750mg per day) it is sold and promoted for these effects as a natural tranquilizer. It is also touted as increasing Human Growth Hormone levels and is popular among body builders. Take GABA if you have a feeling of having had two cups of espresso.

MS patients have shown to have low levels of GABA and glutamic acid.


Relief from stress, tension and depression, very useful in treating epilepsy and several other neurological disorders. Effective in reducing the wrinkles and is also known for its anti-aging effect. It acts as a muscle relaxant and provides relief from stress and fatigue. Some of the health experts say that GABA plays a vital role in the breakdown of fats in the human body. Controlling high blood pressure and in some cases it is found very effective in reducing chronic arthritis and back pain. GABA being an amino acid plays a vital role in maintaining the production of certain hormones in the human body. It regulates many hormones of the body. Regulation of fat molecules.


Endocrine hormones


Let’s have a look at the most important hormonal work force, the steroids, which are provided by our adrenal glands. In chronic disease, chronic stress, or chronic emotional upset they become depleted.


Steroid hormones get their name by four cyclic carbon rings (steroid structure)


They run our metabolism (glucosteroids), water household (mineralosteroids), and reproduction (sex hormones). They are built by pregnenolone and DHEA.


Glucosteroids: cortisol increases blood sugar, suppresses the immune system, metabolizes fat, protein, and carbohydrates. It also decreases bone formation

Mineralsteroids aldosterone influence on salt and water balances. The primary mineralocorticoid is aldosterone

Sex hormones estradiol and testosterone, progesterone. They are all more than sex hormones




The most important steroid.

Because of stress depletion, the adrenals have to be treated first in Energy Medicine. Progesterone, for instance, an important steroid hormone, functions as a pool for stress hormones as well as sex hormones. It is an anti cancer hormone since it keeps estrogen in check. It could be easily depleted by chronic stress, emotional stress, chronic illness, and inflammation. Low Progesterone levels cannot keep estrogen in check. This results in estrogen dominance with development of all kinds of disease.


A loss of hormonal balance, as occurs with aging, plays a predominant role in mental and emotional symptoms and in all illness. Restoration is ideally achieved through natural hormonal replacement therapy.


Progesterone the most important controller

Progesterone is the parent or precursor of estrogen in the ovaries and the parent to cortisol and aldosterone in the adrenal glands. The adrenal glands manufacture progesterone from its precursor cholesterol. Progesterone converts into testosterone, all androgens, and other adrenal hormones, making it extremely important for reasons far beyond its role as sex hormone, without it we could not cope with stress and our body fluid and kidney control would cease to function.


Progesterone postives:

  • Protect the endometrium
  • Insure the optimal function of uterus
  • Anti-cancer hormone. It keeps estrogen in check
  • Prevent water retention
  • Help use fat for energy at the cellular level
  • Serve as a natural anti-depressant
  • Create a calming effect on the body
  • Help eliminate sleep disorders
  • Help keep insulin release in check and maintain even blood sugar levels
  • Prevent unmediated overgrowth of the endometrium/cancer 
  • Prevent unmediated breast tissue overgrowth/cancer
  • Maintain sex drive
  • Maintain normal blood clotting parameters
  • Protect against fibrocystic breasts


Progesterone in men:


·         has a similar effect to the male hormone testosterone. Like testosterone, progesterone enhances your libido, improves your mood, helps keep your weight down and increases muscle mass, gives you more energy, stronger bones, stronger erections and a whole host of other health benefits. Progesterone also increases levels of testosterone in your body and enhances its effects. At the same time, it reduces estrogen and antagonizes estrogen effects.


Progesterone negatives:


are few and easily balanced by estrogen

  • A sedating effect, if used in excess
  • Increased spotting and changes in bleeding patterns
  • Bloating if used in excess
  • Gastrointestinal discomfort
  • Acne, if used in excess
  • Hyperpigmentation of facial skin when exposed to sunlight



Many symptoms of hormonal imbalance are found only in modern society. Stress, processed foods, and other factors unique to modern society are the reasons many women do not get enough essential nutrients to create hormonal balance. It is almost always progesterone, not estrogen that is deficient. Virtually all the commonly known symptoms are those of estrogen dominance. When balance is restored by increasing natural progesterone levels, these symptoms typically disappear (see estrogen dominance)


The negative effects of the growth induced by estrogen unopposed (acting alone), without the balancing effects of progesterone are:


Estrogen dominance


Progesterone keeps estrogen in check. If the estrogen/progesterone ratio is in favor of estrogen (estrogen dominance) disease occurs, especially tumors. Important are “xeno-estrogens” such as heavy metals (mercury), plastics, carcinogenic pesticides, herbicides, and insecticides, which all lead to estrogen dominance. High stress levels such as high cortisol levels also lead to estrogen dominance. Soy bean-derived products and other phytoestrogens act as surrogate estrogens because of their content of genistein. Therefor they are keeping the xeno-estrogens in check. 


  • Increased accumulation of body fat, this is why livestock growers use this hormone
  • Increased water and salt retention
  • Interference with normal insulin release and blood sugar control
  • Increased risk of overgrowth of endometrium (lining of the uterus)
  • Increased risk of overgrowth of breast tissue, and could be a reason for breast cancer
  • Increased risk of depression
  • Increased risk of headaches
  • Increased risk of gallbladder disease
  • Increased incidence of blood clot formation
  • Prostate cancer


Estrogen in women:


·         Primary female sex hormone. Meaning “verve producer”. Development of breasts, pubic and armpit hair, endometrium, regulation of the menstrual cycle and the reproductive system. During the menstrual cycle, estrogen acts to produce an environment suitable for fertilization, implantation, and nutrition of the early embryo.  reduce circulating levels of  FSH and  LH, most oral contraceptives contain a synthetic estrogen, along with a synthetic progestin. The menstrual cycle occurs in three phases: follicular, ovulatory and luteal. The first half of the cycle is known as the follicular phase and the second half of the cycle is considered the luteal phase. Midway through the cycle between days 12 and 16 ovulation occurs, known as the ovulatory phase.


·         Estrogen and other hormones are given to postmenopausal women in order to prevent symptoms of menopause such as hot flushes, vaginal dryness, dry eyes, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating. Fractures of the spine, wrist, and hips decrease by 50–70%


Estrogen in men:

when estrogen levels are unbalanced, the risk of degenerative disease in aging men skyrockets. Excess estrogen contributes to the development of atherosclerosis. Men with even slightly elevated estrogen levels doubled their risk of stroke and had far higher incidences of coronary artery disease. Benign prostate enlargement or prostate cancer had higher blood estrogen levels (and often low free testosterone blood levels).

Insufficientestrogen, on the other hand, predisposes men to osteoporosis and bone fracture.





It is vital for life. Mother of all hormones and derives from Pregnenolone. DHEA is also the parent hormone of estrogen and testosterone. Almost every cell has receptors. Most abundant hormone in the blood stream. When the adrenals are chronically stressed, production of DHEA can be greatly reduced. It is a stress barometer. When stress goes up, DHEA goes down. It regulates the thyroid and pituitary, the thymus, and boosts Human Growth Hormone (HGH).  Almost all the cells have receptors. Important regulator for thyroid, pituitary, thymus, HGH. It is an antioxidant. Building estrogenes and testosterone. Vitamin D enhances DHEA as does MSM and Pregnenolone. 


Lack shows: poor memory, sensitive to noise, anxiety, decreased libido, decreased hair also axillary, pubic. DHEA-sulfate blood test




Other than most hormones it does not log on the cellular membrane but penetrates directly toward the cell nucleus. It is a potent anti-aging hormone for the metabolism, stimulating red blood cell production, checking free radicals, protein synthesis and building muscle mass including the heart muscle. Marked reduced heart attacks both in women and men. It increases excitement and passion, and is an anti- depressant. Exercise will increase testosterone levels. Low levels cause loss of libido both in men and women, erectile dysfunction, and loss of strength and endurance. Testosterone levels decline by age, stress, heavy metals and xenoestrogens  such as plasticides, and bisphenol A (BPA) a plastic compound found as lining in canned food and water bottles. Further by glucocorticoids such as cortisol. I test the free testosterone which represents the amount available for the tissues.




Cortisol is most important in the glucose metabolism. It has katabolic properties. That is it slows and blocks all kinds of metabolic processes including the immune system. It turns immune activities down. Therefore it is used in medicine to control overactive allergic and inflammatory conditions including allergies, sepsis and leukemia.  


·         The following are indications of an excessive cortisol level:
(1) accelerated skin aging and deterioration;
(2) damaged structure and function of mid-brain regions involved in memory; vision, hearing, motor control, sleep/wake, arousal, alertness, and temperature regulation.
(3) impaired wound healing, poor skin quality and excessive scar tissue;
(4) excess fluid retention and puffy, flabby skin.
(5) poor quality of sleep


Cholesterol, Vitamin D, and bile:


 are also steroids


Thyroid hormones,


primary regulators of metabolism triiodothyronine (T3) and its prohormone, thyroxine (T4). They are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism.




production  in pituitary. Insulin like growth factor. Antagonist to insulin. During sleep released. Cell repair.  Zinc is important for production. Sugar is lowering HGH.                        




It lowers blood sugar by opening the cellular doors for sugar. Lowers estrogen. High Insulin levels lower HGH. Insulin has profound impact on aging.




It is secreted from pineal gland. Entrainment on sleep-wake rhythm. Prevents neuronal damage, and nuclear and mitochondrial DNA damage. Boosts NK cells.

found in animals, plants, fungi and bacteria. It is a powerful antioxydant with a particular role in the protection of nuclear and mitochondrial DNA. Against mitochondrial oxidative stress. When humans consume foods rich in melatonin such as banana, pineapple and orange the blood levels of melatonin significantly increase



Further neurotransmitters




90% found in the gastro-intestinal tract. Responsible for digestion, well being, happiness, appetite, sleep, mood. Serotonin and Dopamin are antagonists. This suggests that the dopaminic substantia nigra in the brain may be adversely influenced by food intake and the intestine-related serotonin.




reward motivated behavior. Most types of reward increase the level of dopamine in the brain, and a variety of addictive drugs increase dopamine neuronal activity. Other brain dopamine systems are involved in motor control. Parkinson`s disease, a degenerative condition causing tremor and motor impairment, has been related to the loss of dopamine-secreting neurons in the midbrain area called the substantia nigra. There is evidence that schizophrenia involves highly altered levels of dopamine activity, and the antipsychotic drugs that are frequently used to treat it have a primary effect of attenuating dopamine activity. Attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS) are also believed to be associated with decreased dopamine activity. The connection between the substantia nigra and the corpus striatum is critical to produce smooth, purposeful movement. Loss of dopamine in this circuit results in abnormal nerve-firing patterns within the brain that cause impaired movement. People with Parkinson's also have loss of the nerve endings that produce the neurotransmitter  Norepinephrine, which is closely related to dopamine




kick starts metabolism. Flight or fight reaction. Bronchodilation. Cardiac arrest.




vigilance, paying attention to as opposed to Dopamine for cognitive alertness. Alpha 1 blockers relax certain muscles and help small blood vessels remain open. They work by keeping the hormone norepinephrine (noradrenaline) from tightening the muscles in the walls of smaller arteries and veins. Blocking that effect causes the vessels to remain open and relaxed. This improves blood flow and lowers blood pressure.

Because alpha blockers also relax other muscles throughout the body, these medications can help improve urine flow in older men with prostate problems.

α2-blockers have found medical uses in treating depression; the tetracyclic antidepressants mianserin and mirtazepin are α2-blockers, although their efficacy as antidepressants may come from their activity at other receptor sites.

Mechanistically, α2-blockers significantly increase adrenergic, dopaminergic and serotonergic neurotransmitters, and induce insulin secretion and decreases blood sugar levels.




Principal neurotransmitter of the autonomic nervous system and peripheral motor system.

It is also a transmitter of the central nervous system (CNS)



Hormonal Therapy




Where is Pregnenolone formed?


Pregnenolone is the precursor of many steroid-hormones. It is mainly produced in the adrenals albeit it is also synthesized in the brain, liver, skin, testicles, ovaries, and retina.


Live cycle of Pregnenolone  


In youth we find highest amounts of Pregnenolone. Decrease starts at the age of 25  initiating a steady decrease along with the aging.
At 75 years the body produces about 60% less Pregnenolone versus age 30. This is why Pregnenolone is an important  indicator for aging .  

Because it is the “grand mother” substance in the functional chain of hormones it is responsible for the steady overall decrease of power of our body when we grow older, because over the life time span of a person this hormone is depleted by the aging process. That is why sufficient amounts of Pregnenolone are a guard against complaints going along with aging.


General impact of Pregnenolone on our organism


Pregnenolone strengthens the protecting myeline sheath of our nerve cells, which are constantly attacked by toxic environmental substances.
It improves the over all feeling, mental functions, improves vigilance, stimulating clear and swift thought processing, elevates concentration and cognitive functions, alertness, supports creativity, keeps brain functions on optimal levels, triggers desire to learn and to try out new things. It improves psychic energy levels as well as speech and visual capacity. Degenerative effects of aging are slowed and the over all aging of memory is reduced.

Stress increases cortisol levels, inhibiting and compromising the immune system, triggers calcium loss and possible Osteoporosis.

Pregnenolone in combination with Melatonin has proven to be a potent player against cortisol in order to manage stress.


How does lack of Pregnelonone affect our body?


Lack of Pregnenolone provokes lack of energy, weak memory, causes visual and acoustic  impairment, arthritis, heart disease, memory loss, mood fluctuations such as depression, and reduces libido.


Pregnenolone and brain function


Pregnenolone levels are multi-fold higher in the human brain than in the blood. This highlights the importance of the hormone for healthy brain functioning.
As a neuro-steroid, Pregnenolone is formed in brain cells. However, its production decreases rapidly with aging.
Pregnenolone belongs to the most effective known steroids responsible for both brain and memory power. It improves the memory and learning phase. Pregnenolone modulates diverse signal transfers from neuron to neuron and thus largely influences learning and memory processes.
Pregnenolone interferes with multiple brain receptors such as GABA (Gamma-amino-butyric acid) and NMDA (N-Methyl-D-Aspartate), whereas the latter plays an important role for signal transfer (e.g. synaptic switch boards)  between nerve cells including all their prolongations (neurons) which influence both learning and memory qualities.
Aging goes along with loss of NMDA-Receptors and therefore is in part responsible for loss of learning and memory . Pregnenolone also triggers acetylcholine, which also impacts memory.
New studies show that minute dosages of Pregnenolone could have astounding memory improvement. Among all steroid hormones Pregnenolone seems to render the best memory improvement and could be administered in 100 times smaller dosages than other memory boosting substances (post learning memory function). According to American research Pregnenolone has proven to enhance memory even after brain injury.

Pregnenolone reduces psychic and physical fatigue.
More energy is gained on the psychic level. Function of sensory organs such as ears and eyes can be improved. Colors appear brighter and clearer. Contours and objects become sharp edged, so that they can be visualized better.


Diseases treatable with Pregnenolone


Pregnenolone has shown positive results both in psychic and organic disease.
It has been substantially helpful in depression and manic depression disorder. Further in depressive moods (dysthymia) with signs of helpnessness, tiredness, low self steem, sleeping and eating disorders, lacking motivation, and chronic-fatigue-syndroms (CFS)

It is an option in cases of Addison, Parkinson, Alzheimer, multiple sclerosis, nerve injury by accidents, burns, and electrical shock.
Pregnenolone slows down skin aging, smoothing the skin, builds up muscles, and boosts the immune system. In diabetes it helps renewing the Beta cells and can be suggested for people beyond 40 years of age.

Pregnenolone has anti-inflammatory qualities and is useful against rheumatic diseases of joints (arthritis), of the spinal column, and spondylitis ancylotica. Versus cortisol it has no side effects.
It is also helpful against heart disease, high cholesterol, visual- and hearing impairment, pre-menstrual syndrome, benign prostate hyperplasia, or autoimmune disease such as  Lupus erythematodes or scleroderma.
The older and unhealthier the patient, the more the benefit of Pregnenolone can be felt .


Which hormones are modulated by Pregnenolone?


Foremost Pregnenolone is the precursor of the adrenal hormone Dehydroepiandrosteron (DHEA). Therefore it may be combined with DHEA without hesitation.
Whereas DHEA is considered the „mother“ of all hormones, Pregnenolone may be called „grand mother” of all steroid hormones. In the human body over 150 steroid hormones derive from  Pregnenolone 


Does Pregnenolone have negative impact on other hormones?


In the body Pregnenolone is circulating as water soluble Pregnenolone-sulfate.
In progressed age Pregnenolone may be administered in tandem with other hormones such as DHEA without hesitation or fear, because there is only minute transformation of Pregnenolone into  DHEA or into other steroid hormones. With progressing age, enzymes needed for that transformation are excreted in minute amounts only. That shows that there is hardly any transformation. Consequently there will not be overdosing.


Does Pregnenolone have positive interaction with other hormones?


Pregnenolone together with DHEA enhances health all over and is also applied in combination with Melatonin as an anti-aging remedy.

Specifically in traditional estrogen hormonal replacement therapies, estrogen dosage could be minimized by Pregnenolone in combination with DHEA and Melatonin. That is how adverse estrogen side effects need not to be feared. Bone and heart diseases as well as typical symptoms of menopause such as hot flashes and sleeping disorders could be treated even with lowest estrogen substitution.


Ways of Pregnenolone application


Pregnenolone must be compounded as capsules by a pharmacy according to medical prescription. Pregnenolone cannot be administered as herbal precursors because our body cannot synthesize them into Pregnenolone.


What dosage is needed?


10 mg for light memory complaints up to 100mg per day if necessary. Adults over 40 years of age take an average of 10mg per day. Over 50 years of age 25 mg, and over 60 years 50 mg Pregnenolone.
This dosage secures ideal hormonal Pregnenolone levels as we have it at the age of  20-30.

Aging slows down. It should be taken in the morning before breakfast.


Which are the side effects of Pregnenolone?


Unwanted side effects are not known. As a caution it should not be taken during pregnancy and lactation.


Pregnenolone against anti-aging ?


It is evident that Pregnenolone renders marked improvement of life quality, over all health, and well being. Thus it can postpone aging processes.
Since Pregnenolone is transformed into Progesteron, DHEA, Testosterone, and estrogen it enhances longevity by slowing the aging process and plays a remarkable role for positive life quality all over.

Pregnenolone and Mental Function

Pregnenolone is the precursor (building-block) for all other steroid hormones. It is converted directly into DHEA and/or progesterone. DHEA converts to testosterone and estrogens; progesterone converts to estrogens, cortisol, and aldosterone. It is this succession of conversions that makes human life possible. Without pregnenolone, there can be no human steroid hormone production.

Made from cholesterol, pregnenolone is a natural steroid hormone produced primarily in the adrenal glands, but in smaller amounts by many other organs and tissues of the human body, including liver, brain, skin, gonads, and even the retina of the eye.

Like many health-promoting hormones, levels of pregnenolone drop with age. Although the data are not as abundant or definitive for pregnenolone as they are for DHEA, Dr. Eugene Roberts, a pioneer in hormone research, believes that the age-related drop in pregnenolone is as dramatic as the drop in DHEA. At 75, our bodies typically make 60% less pregnenolone than at age 35. This is a point of great concern, considering pregnenolones numerous protective, health-promoting properties.


Energizing, Anti-stress Benefits

Some of the earliest investigations of pregnenolones many benefits showed it to be an energizing, anti-stress biochemical. During the 1940s, Drs. Pincus and Hoagland gave 50-100 mg/day of pregnenolone to various types of factory workers, as well as pilots and students trained to use a flight simulator. The factory workers noted improved production rates while taking pregnenolone. They felt less fatigued, better able to cope with their jobs and experienced an enhanced sense of happiness and well-being. Interestingly, workers in stressful job environments improved more with pregnenolone than those with less demanding tasks.

The flight simulation machine was designed to test hand-eye coordination, learning, memory and stamina. The subjects were to 'fly' the 'plane' correctly, avoiding obstacles and crashes. Half the subjects were airplane pilots; half were not. Tests conducted over several weeks showed that the ability of all subjects to 'fly' the simulated airplane improved significantly after taking 50 mg pregnenolone before each test run. The improvement was especially noticeable after the subjects had taken pregnenolone for at least two weeks. This suggests pregnenolones anti-stress benefits may be cumulative. Also, the professional pilots reported that they performed better in their real flying jobs and that they suffered less fatigue during their pregnenolone-supplementing period.

Pro-memory Effects

Animal studies by Isaacson, Flood, Morely and Roberts have shown that injection of as few as 15 to 145 molecules (!) of pregnenolone directly into the areas of the brain that are thought to www.e memory improved the ability of mice to more quickly remember the way out of a maze that they had run before. Preliminary results of St. Louis School of Medicine researcher R. Sih have shown definite memory enhancement with pregnenolone. Dr. Sih gave 500 mg pregnenolone or a placebo to men and women three hours before they were asked to perform standard memory tests. Pregnenolone resulted in improved memory in both men and women, improved spatial memory and perception in men, and improved verbal recall memory in women.

Mood Elevation

Pregnenolone is known to modulate at least two key nerve receptor systems in the brain: NMDA receptors and GABA receptors. NMDA receptors, which weaken with age, are involved in learning, memory, and alertness. Pregnenolone enhances NMDA receptor function. GABA receptors promote relaxation, mental slowing, sedation and sleep. Benzodiazepine drugs (Valium, Librium, Xanax, etc.) activate GABA receptors, while pregnenolone inhibits GABA receptors. Thus, too little NMDA activity combined with excessive GABA activity would tend to promote mental sluggishness and depression. Since pregnenolone raises NMDA activity and lowers excessive GABA activity, pregnenolone seems to be a natural antidepressant. Indeed a recent study of 27 depressed patients found that their cerebrospinal fluid (which circulates through the brain and spinal cord) was significantly lower in pregnenolone than in 10 non-depressed volunteers. Cerebrospinal fluid levels are generally believed to accurately reflect levels of various biochemicals in the brain.


Anti-arthritis Effects

During the 1940s, pregnenolone was used successfully as a treatment for rheumatoid arthritis. A 1950 review article on pregnenolone reported on a study by Henderson and colleagues which found that 300 mg pregnenolone/day for 40 days resulted in a significant decrease in joint pain, tenderness, and spasticity, with improved strength and range of motion. Another study by Freeman and colleagues, with 64 patients, used 500 mg of pregnenolone daily for periods of 2 to 30 weeks. 24 patients showed striking improvements, and 20 showed minor improvements.

Unfortunately, the advent of the 'wonder drug' cortisone (Cortisol) in the 1950s caused pregnenolone to be passed by for arthritis treatment, since pregnenolones results were much slower to manifest. 'Coincidentally', pregnenolone couldnt be patented by the drug companies whereas synthetic variants of cortisone could be (and were) patented. By the time the nightmarish side-effects of excessive cortisone were widely known by the medical community in the 1960s (these side effects could include psychotic breakdown, adrenal failure, and even death), pregnenolone had been completely forgotten.

Pregnenolones Cortisol-neutralizing Power

Small amounts of cortisol are essential to promote health and even for life itself. Yet under the prodding of chronic stress and aging, our adrenal glands often over-produce cortisol. Indeed, cortisol is the only steroid hormone whose levels tend to increase with age. The level of all other steroids, including pregnenolone, tend to decrease (often radically) with age. Excessive cortisol promotes a host of negative side-effects. High cortisol levels promote depression, as does chronic, unremitting stress in many people (which results in chronically elevated cortisol). Experimental subjects such as factory workers and airplane pilots who were given pregnenolone under stressful conditions actually reported an enhanced sense of well-being and happiness.

Excessive Cortisol

The following are indications of an excessive cortisol level:
(1) accelerated skin aging and deterioration;
(2) damaged structure and function of mid-brain regions involved in memory;
(3) impaired wound healing, poor skin quality and excessive scar tissue;
(4) excess fluid retention and puffy, flabby skin.
(5) poor quality of sleep.

Most of these adverse effects of cortisol are directly counteracted by pregnenolone. For example, Papa and Kligman reported in 1965 that topical application of a pregnenolone-containing skin cream restored youthful properties to aged skin.

Experiments with humans and animals show that pregnenolone enhances the function of the same pro-memory areas of the mid-brain that are damaged by cortisol. A 1994 report by Guth and colleagues found that pregnenolone actually promoted successful healing of otherwise crippling spinal cord injuries in rats. Ray Peat, Ph.D., has reported successful use of pregnenolone to rid the body of cortisol-induced excessive fluid and puffiness, promoting a more lean and taut, youthful appearance to the face. Steiger (1993) used a mere 1 mg of pregnenolone in human volunteers to increase the restorative delta, slow-wave, stage IV sleep. (Larger doses of pregnenolone taken inappropriately at night may, however, also promote insomnia through 'over-energization'). Thus, pregnenolone seems in many ways to be a natural 'antidote' to the 'dark side' of cortisol, which tends to manifest ever more with aging and chronic stress.

Chemo-protective Action

A major determinant of the bodys ability to detoxify poisonous chemicals -- such as pesticides, medical drugs, industrial contaminants and auto exhaust -- is the health and effectiveness of the Cytochrome P450 enzyme system in the liver. This is one of the most broad-spectrum, universal detoxifying enzyme systems possessed by all mammals, including humans. Moderate levels of cortisol (the 'state-of-siege' anti-stress hormone) promote the activity of this detox system. However, larger amounts of cortisol (which is all-too-often over-produced by our adrenal glands due to aging or prolonged stress) degrade the P450 systems anti-toxin effects. Although pregnenolone does not affect the rate of synthesis of the enzymes in the P450 system, it does stabilize these enzymes against the digestive activity of liver proteolytic enzymes which would tend to break down the P450 enzymes. Pregnenolone thus increases overall P450 detox enzyme power by promoting conservation of existing P450 enzymes.


Fortunately, pregnenolone is amazingly safer than other steroids. Pregnenolone researchers working with both human and animal subjects since the 1940s have consistently commented on pregnenolones virtual absence of toxicity. For example, the classic review article on pregnenolone by Henderson and colleagues in 1950 states: 'It [pregnenolone] has an extremely low order of toxicity; [it] has not shown any adverse effects on endocrine [hormone] physiology ....'

Pregnenolone has been given orally to humans at doses as high as 500 mg/day for as long as 30 weeks without evidence of adverse effects. Mice given 5 grams (1/6 ounce) per kilogram (2.2 pounds) of body weight suffered no ill effects. This would be equivalent to a 154 pound (70 kilogram) human ingesting 350 grams (approximately 3/4 pound) per day! In a long-term study, mice that were given one gram pregnenolone per kilogram of body weight three times weekly for 50 doses suffered no toxic reactions -- including no changes in the size and condition of offspring produced after the 50 doses.

In one human study, eight people received 50 to 150 milligrams per day by intramuscular injection for 75 days, with no reported side effects. Dr. Eugene Roberts gave 20 Alzheimers patients 525 mg/day for three months with no toxicity. During rheumatoid arthritis experiments with pregnenolone, Dr. H. Freeman and colleagues gave 500 mg pregnenolone/day for up to 30 weeks, with no toxicity. And Drs. Pincus and Hoagland, two of the pioneer researchers on pregnenolone use by humans in the 1940s, found no toxic reactions with pregnenolone used by hundreds of men and women at dosages of 100 mg/day for four months.


The classic studies on pregnenolone and stress in the 1940s by Pincus and Hoagland generally used only 50 mg/day to achieve excellent results, while arthritis studies typically used 200-500 mg daily. Thus, although pregnenolone appears amazingly safe and beneficial, there are still many unanswered questions regarding proper dosage, metabolism, and clinical effects. Keeping these uncertainties in mind, here are some recommendations for dosage.

For those wishing to err on the side of caution, 50 to 100 mg pregnenolone per day would probably be suitable for use without physician monitoring. Perhaps an additional safety margin (for this already amazingly-safe substance) could be achieved through discontinuing use for one week every month. Those wishing to use the higher, anti-arthritis doses (200 - 500 mg/day) should probably do so only under the supervision of their physician, even though many human clinical studies with arthritis at these dosages yielded no problems or toxicities. Morning is the perfect time to take pregnenolone, and a single daily dose is probably best, since pregnenolone is fat-soluble, and probably follows the circadian highs and lows of DHEA and cortisol (highest in the morning, with a drop to baseline by late afternoon). On an anecdotal note, there have been patients taking 100 - 1,000 mg pregnenolone/day intermittently since 1987, with no discernible negative side effects.


While there has been no definite information published as to who should not take pregnenolone, on theoretical grounds, a few cautions can be suggested. Since pregnenolone (especially at high doses) may (in some people) increase estrogen or testosterone levels, I believe that men with prostate cancer (which may be worsened by testosterone) and women with breast or ovarian cancer (which may be worsened by estrogen) should probably take pregnenolone only with their doctors consent and supervision. Men with high PSA (prostate specific antigen) blood levels (possible indicator for undiagnosed or future prostate cancer) should also proceed with caution with pregnenolone use. Lastly, because of pregnenolones anti-GABA, pro-NMDA action, persons known to suffer from epileptic seizures or who are taking an anti-seizure medication such as Dilantin, Depakote or Tegretol should probably only use pregnenolone with their doctors supervision. Finally, as we age, the body produces ever-less of the enzyme which converts pregnenolone to DHEA. Thus, while supplementary pregnenolone taken during middle age and beyond will produce at least some normalization back toward more youthful (and healthful) levels of other steroid hormones, pregnenolone will not completely substitute for other steroid hormone supplements in those with medically demonstrated needs for various specific steroids i.e., DHEA, cortisol, estrogen, etc.

Davison, R., et al. Effects of delta 5 pregnenolone in rheumatoid arthritis. Arch Int Med 85: 365-88, 1950.

Flood, J. et al. Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures. Proc Nat Acad Sci USA 92: 10806-10, 1995.

Freeman, H., et al. Therapeutic efficacy of delta 5 pregnenolone in rheumatoid arthritis. JAMA 143: 338-44, 1950.

George, M., et al. CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI Biol Psych 35(10): 775-80, 1994.

Guth, L., et al. Key role for pregnenolone in combination therapy that promotes recovery after spinal cord injury. Proc Nat Acad Sci USA. 91(25): 12308-12, 1994.

Henderson, E., et al. Pregnenolone. J Clin Endocrinol 10: 455-74, 1950.

Maione, S., et al. Pregnenolone sulfate increases the convulsant potency of NMDA in mice. Eur J Pharmacol 219 (3): 477-9, 1992.

Majewska, et al. Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons. Neuroscience Letters 90: 279-84, 1990.

Pincus, G. and Hoagland, H. Effects of administered pregnenolone on fatiguing psychomotor performance J Aviation Med 15: 98-115, 1944.

Pincus, G. and Hoagland, H. Effects on industrial production of the administration of delta 5 pregnenolone to factory workers. Psychosom Med 7: 342-46, 1945.

Regelson, W. and Colman, C. Pregnenolone: 'The Superhormone for Your Brain' [material on Dr. R. Sih] in The Superhormone Promise, Simon and Schuster, 1996.

Roberts E. Pregnenolonefrom Selye to Alzheimer and a model of the pregnenolone sulfate binding site on the GABA-A receptor. Biochem Pharmacol 49: 1-16, 1995.

Steiger, A., et al. Neurosteroid pregnenolone induces sleep EEG changes in man compatible with inverse agonistic GABA-A receptor modulation. Brain Res 615: 267-74, 1993.

Warner, M. and Gustaffson, J. Cytochrome P450 in the brain: neuroendocrine functions. Front Neuroendocrinol 16(3): 224-36, 1995.

Wu, F., et al. Pregnenolone sulfate: a positive allosteric modulator at the NMDA receptor. Mol Pharmacol 40: 333-6, 1991.