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Pregnenolone is a natural hormone that has been largely overlooked due to its more well-known steroidal cousins, cortisone, progesterone and DHEA.
Like other steroid hormones, it is made from cholesterol found in the tissues of the adrenal glands, liver, ovaries, testicles and other organs. Pregnenolone is an absolutely critical hormone, since it is the base hormone from which ALL OTHER HORMONES are derived. It is really the mother of all hormones.

Combination therapy
Current hormone therapy deals with direct replacement of specific hormones. However, it is becoming accepted that using precursors to stimulate the natural production of needed hormones may be more effective as the natural balance of hormones is not disrupted, and side effects are reduced. Keep in mind, however that as the body ages, enzymes required to convert pregnenolone to other hormones like DHEA, also decrease.

Consequently, taking only pregnenolone will not necessarily raise other hormone levels.For this reason, combined hormonal supplementation may be more effective

The Physiology of pregnenolone
Human bodies manufacture about 14mg of pregnenolone daily and it is then converted into numerous other hormones, depending on need. Pregnenolone is very water soluble, thus enabling it to circulate in the blood. It has very low toxicity and virtually no side effects and seems to help:
•  autoimmune diseases 
•  immune system weakness
•  memory disorders  
•  mood disorders
•  chronic fatigue 
•  hormone based disorders
•  rheumatoid arthritis
•  stress
•  nerve trauma 
•  psoriasis
•  skin rejuvenation
•  multiple sclerosis
•  osteoporosis   
•  prostate disease.

It is well known that exposing the body to stress can cause adrenocortical depletion.

In other words, when we have to cope with high stress situations our adrenal glands manufacture more adrenalin. If the stress is prolonged enough, the glands become exhausted, resulting in not only physical fatigue, but also depression and susceptibility to infection. Pregnenolone was tested with people with stressful job situations, such as airline pilots, and confirmed that psychomotor performance improved. It also enhanced the performance of various labour orientated jobs, including lathe workers and leather cutters. Performance was assessed on the basis of overall productivity, quality of work, frequency of mistake and mental and physical fatigue.

Rheumatoid arthritis
Some of the early tests conducted with pregnenolone dealt with its effect on rheumatoid arthritis. Mobility was enhanced, and pain and tenderness decreased. These early tests used relatively high doses and injections, but were stopped when hydrocortisone was discovered, which was more effective.

However, pregnenolone could easily be used with anti-inflammatory drugs to enhance the healing of inflamed nerve endings by initiating normal myelin sheath synthesis (1) and reducing pain.

Enhanced brain function
Factory workers taking 50mg pregnenolone daily experienced positive results such as enhanced productivity with less fatigue and increased coping skills (2). Pregnenolone can effect brain function in a very specific way. It acts as a GABA antagonist, which simply refers to its ability to prevent certain chemicals from attaching to GABA receptors. When GABA receptors are inhibited, sensations of relaxation or sleep are also inhibited.

In other words, pregnenolone creates a stimulatory effect.

It is believed that decreased levels of pregnenolone with aging prevents our ability to think fast and retrieve stored information. A 1995 study with rats found that small amounts of pregnenolone improved memory function(3).

We know that pregnenolone blocks GABA receptors and interferes with the tranquillising effects of sedatives. A study conducted in 1993 found that 1mg of pregnenolone prior to bed causes elevated delta sleep, or slow wave sleep (4)
This particular stage of sleep is considered a deep sleep and is connected to rapid eye movement sleep, the stage during which we dream.

A study using pregnenolone for patients with lupus found marked improvement in symptoms, including lessening of joint pain & reduction of rash which typically accompanies the disease (5).

It is believed that pregnenolone works for lupus by converting to DHEA which stimulates the production of interleukin-2, a critical component of the immune system which is low in people suffering from lupus (6).

Hormone replacement therapy
As we age, most of our hormones decrease. Considering the fact the pregnenolone converts to DHEA and DHEA subsequently converts to oestrogen and androgens, a fascinating question arises. Instead of using high doses of oestrogen, why not give the body oestrogen precursors and let the body make the amount of oestrogen that it needs?
The idea of using hormone precursors to stimulate an ageing endocrine system is gaining acceptability.

Oestrogen dominance occurs when a progesterone deficiency occurs, giving pregnenolone to enable the body to makes its own level of progesterone makes good sense.

Dosing ranges between 10mg to 100mg and is absorbed orally or from topical creams

1) Progesterone synthesis and myelin formation by Schwann cells Science 268:(5216),1500-03, 1995
2) Effects on industrial production after giving pregnenolone to factory workers
Psychosom Med 7:342-346;1945
3) Pregnenolone enhances post-training memory processes when injected in very low doses Proc Nat Acad Sci USA 92(23),10806-10;1995
4) Neurosteroid pregnenolone induces sleep-EEG changes in man Brain Res 615:267-274;1993
5) The use of pregnenolone in various clinical disorders  J Clin Endocrin 11:559-577;1951
6) DHEA in multiple sclerosis: Biological Role of DHEA M Kalimi New York 1990

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