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PREGNENOLONE
THE ULTIMATE
HORMONE
PRECURSOR

RITA ELKINS, M.A., M. H.

WOODLAND PUBLISHING
Pleasant Grove, UT
 ©1997.
Woodland Publishing, Inc.
PO. Box 160
Pleasant Grove, UT 84062

The information contained in this book is for educational purposes only and is not
recommended as a means of diagnosing or treating an illness. All matters
concerning physical and mental health should be supervised by a medical profes-
sional knowledgeable in treating that particular condition. The publisher and
author neither directly nor indirectly dispense medical advice nor prescribe any
remedies, natural or otherwise. They do not assume responsibility for those who
choose to treat themselves.
 TABLE OF CONTENTS

INTRODUCTION 5

PREGNENOLONE: A DEFINITION 6

THE PHYSIOLOGY OF PREGNENOLONE 9

THE VALUE OF PREGNENOLONE 10

PREGNENOLONE INHIBITORS 11

THERAPEUTIC APPLICATIONS OF PREGNENOLONE 13

IS PREGNENOLONE SUPPLEMENTATION

EFFECTIVE? 25

CONCLUSION 27

ENDNOTES 29
 Digitized by the Internet Archive
In 2022 with funding from
Kahle/Austin Foundation

https://archive.org/details/pregnenoloneulti0000elki
 INTRODUCTION
Pregnenolone (also known as “preg”) is a natural hormone which
has recently emerged as an overlooked steroidal compound with var-
ious therapeutic properties. It has become an important member of
a “wonder hormone” category which includes over-the-counter
hormones not previously used for their medicinal and antiaging
properties. After 1950, the medical establishment ignored the use of
pregnenolone as an impressive medicinal compound because the
principle emphasis of scientific inquiry involved the corticosteroids.
Unfortunately, hormonal compounds belonging to the cortisol fam-
ily became the primary focus of medical research and application.
Today, most of us are aware that while steroid treatments can be
remarkably effective in the treatment of inflammatory diseases, they
come with serious and potentially dangerous side effects. Studies
involving cortisol and its derivatives are numerous and appear in
medical literature worldwide. In contrast, pregnenolone has received
relatively little attention in professional circles—an omission which
is due in part to the fact that pregnenolone, like DHEA and mela-
tonin, is not a patented medicine and is available without a pre-
scription.
Studies conducted with pregnenolone strongly suggest it has
impressive physiological merits which should be further investigat-
ed. These studies reveal the hormone’s impressive ability to stimulate
6 PREGNENOLONE

healing and enhance brain function. In addition, there is an impor-

tant probability that pregnenolone can be used for ailments such as
lupus, psoriasis, prostate disease, multiple sclerosis, PMS and sclero-
derma. The possibility of combining pregnenolone with other stan-
dard drug therapies such as anti-inflammatory agents or other
steroidal compounds also has some very interesting implications. It
may help to decrease the need for drug dosages that come with sig-
nificant side effects.
At this writing, pregnenolone research is still in its infancy. What
little we do know about this compound demands continued and
long-term testing. The fact that this fascinating hormone has healing
potential for a number of devastating diseases must not be over-
looked. As stated in Biochemical Pharmacology (1995), “there are
many fascinating investigative avenues dealing with preg that are
wide open and ready for development, It is hoped that this com-
mentary will encourage some others to enter this field.”!

PREGNENOLONE: A DEFINITION
Technically speaking, pregnenolone is a steroidal compound
derived from cholesterol. Most of us perceive cholesterol as negative
due to its profound link to cardiovascular disease, but we have to also
understand that cholesterol is essential for the maintenance oflife. It
is absolutely necessary for the production of steroidal hormones such
as pregnenolone because cholesterol is the lipid compound that
serves as the building block of all steroids. Even though most of us
are trying to nix cholesterol from our diets, we need to keep in mind
that the human body cannot exist without it.
Pregnenolone, like other steroid hormones, is synthesized from
cholesterol found in tissues of the adrenal glands, liver, ovaries, tes-
ticles, and other organs. Special chemical catalysts called enzymes
enable the body to covert cholesterol into pregnenolone. Along with
other steroids, it is actually manufactured in the powerhouse section
 THE ULTIMATE HORMONE PRECURSOR U

of the cell, the mitochondria. As determined by the needs of our

body, cholesterol is transported to the mitochondria where it is
chemically changed into pregnenolone.’

THE ULTIMATE STEROID PRECURSOR

Steroids are part of a chemical compound class which includes

hormones such as estrogen, progesterone, testosterone, cortisol,
DHEA and pregnenolone. Each one of these hormones belong to
the same chemical family, but each plays a very different role within
human physiology. Pregnenolone is one of the more fascinating
steroidal compounds. It is very easily converted into DHEA, which
subsequently changes to estrogens and other steroids. For this rea-
son, pregnenolone is considered a parent steroid compound.
Virtually all steroid hormones are produced from pregnenolone,
making it the ultimate in hormone precursors. Some experts even
refer to pregnenolone as being pleiotropic, a genetic term referring
to the ability to control more than one genetic characteristic by a sin-
gle gene.
To date, scientists have discovered over 150 steroid compounds.
The impressive benefits of the compound DHEA, a derivative of
preg, are now beginning to emerge and data is being compiled. Its
description as one of the most important antiaging and antidisease
compounds is gaining credibility. While taking DHEA or other hor-
mones in their primary state may be warranted, using pregnenolone
as a precursor to the synthesis of DHEA may be advantageous in cer-
tain situations, and sometimes even preferable. Combining DHEA
with pregnenolone may be even more valuable when attempting to
achieve desired hormonal levels.
Current hormone therapies deal with the direct replacement of
certain biochemical compounds back into body tissues. However, it
is becoming accepted that using precursors to stimulate the produc-
tion of needed compounds may, in fact, be more effective.
Apparently, there is evidence to support that when such stimulation
8 PREGNENOLONE

occurs, the natural balance of hormones is not disrupted. In other

words, when we take a drug like prednisone, for example, we bypass
body systems and negatively tip our endocrine system scales, causing
a myriad of undesirable side effects. If the production of natural cor-
tisol could be sufficiently stimulated by introducing precursors to
enhance its chemical synthesis, the dangers associated with the phar-
maceutical form would not be such an issue. Keep in mind, howev-
er, 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 DHEA levels. For this
reason, combined hormonal supplementation may be more effec-
tive. Tests have confirmed, however, that oral administration of preg-
nenolone can result in elevated blood levels of other steroid metabo-
lites or in the stimulation of steroid receptors.

A BRIEF HISTORY OF PREGNENOLONE

During the last twenty years, adrenocortical hormones like preg-

nenolone have been placed on the back shelf of medical research.
But they were not always so ignored. In the late 1930s and early
1940s, pregnenolone was first extracted from animal tissue, and a
few subsequent studies on the compound emerged in the 1950s.
Throughout this time, preg was used in various clinical tests in
dosages ranging from 50 to 600 mgs per day. While these tests may
not pass today’s rigorous scientific standards, their collective data
indicates that the compound has obvious medicinal properties and
physiological merits.
Hans Selye, well known for his studies on the effects of stress on
the human body, was one of the first “pregnenolone pioneers.” He
concluded that the preg compound may be much more valuable
than anyone previously assumed. Throughout the 1940s, a number
of studies were conducted investigating the effects of pregnenolone
and stress. When taking 50 mg of pregnenolone every day, a group
of factory workers experienced positive results like enhanced pro-
 THE ULTIMATE HORMONE PRECURSOR S)

ductivity with less fatigue and increased coping skills.? The study
concluded that pregnenolone supplementation was a significant
inhibitor of fatigue, especially in environments where stress levels are
high and demands significant. In addition, the study did not find
any undesirable side effects associated with the administered dosage.‘
By 1950, research concerning pregnenolone continued and
invariably the consensus was that continuing research on this hor-
mone was more than warranted. Sadly though, during the last few
decades little attention was given to this remarkable hormone. As
mentioned earlier, a glut of studies on cortisol, estrogen and testos-
terone have dominated medical literature, while both preg and
DHEA and their therapeutic potential were, in essence, overlooked.
Most of us are acutely aware of the widespread use of cortisone
therapy for inflammatory and asthmatic conditions. While no one
can deny that drugs like prednisone have remarkable therapeutic
properties, it must also be acknowledged that such drugs come with
very serious side effects. In fact, any synthetic hormonal therapy
poses numerous health threats to a variety of body functions, sug-
gesting that pharmaceutical steroidal preparations can interfere and
adversely effect a number of physiological functions. Today, the neg-
ative effects of “steroids” are well known. Unlike steroidal drugs,
pregnenolone appears to offer a host of therapeutic actions without
dangerous side effects.

THE PHYSIOLOGY OF
PREGNENOLONE
The amount of pregnenolone synthesized from cholesterol is
largely determined by hormones which are secreted by the pituitary
gland. The pituitary gland acts as our master hormone computer,
sensing either a deficiency or excess of any number of hormones.
Depending on the levels present, it produces chemical signals which
either stimulate or inhibit hormone production. This delicate hor-
10 PREGNENOLONE

monal balancing act is well-executed by the pituitary gland, which,

ideally, maintains a well-functioning and balanced endocrine system.
While it is currently not possible to determine the exact amount
of pregnenolone we produce, studies conducted in 1967 in England
approximated that male plasma contains ten micrograms per 100
milliliters of pregnenolone, suggesting that most of us would manu-
facture approximately fourteen mg of pregnenolone daily. As is the
case with most other hormones, that figure would drop with age.

WHAT PURPOSE DOES PREGNENOLONE SERVE?

Once it is produced, pregnenolone can be chemically transformed
into more than one substance. Depending on the physiological
needs of our body systems, preg can be metabolized into proges-
terone or DHEA. If it chemically converts to progesterone, it can
then covert to cortisol or aldosterone. Aldosterone is the hormone
which maintains blood pressure. It instructs the kidneys to keep
sodium levels high enough so that fluid pressure within the arteries
and veins will be sufficient to maintain blood pressure. If preg-
nenolone converts to DHEA, it can subsequently further convert to
testosterone or estrogen.

THE VALUE OF PREGNENOLONE

Hans Selye, an early pioneer of steroid research, was one of the
first researchers to stress the fact that unlike other steroids, preg-
nenolone has the capability to participate in a number ofphysiolog-
ical activities. He wrote:

In most respects the compound [pregnenolone] is quantitatively

nor very potent. It distinguishes itself from other steroids, however,
because it possesses so many different activities. Thus, the com-
pound possesses . . . at least in traces . . . every independent main
pharmacological action which has hitherto been shown to be exhib-
 THE ULTIMATE HORMONE PRECURSOR 11

ited by any steroid hormone. In the light of these observations it is

tempting to speculate on the possible role of the compound as an
undifferentiated hormone-precursor form which the organism may
. . . according to its needs . . . produce compounds in which one
effect is particularly developed at the expense of other activities of
the multi-potent parent substance.

Basically, Selye points out that pregnenolone plays a profound role

in the body as a hormone precursor from which steroid hormones
are synthesized according to individual physiological requirements.
In order to facilitate the usage of pregnenolone within human tis-
sue, the compound attaches to one sulfur atom and four oxygen
atoms when circulating in the blood, thus enabling it to become
more water soluble. The Journal of Clinical Endocrinology (1950)
points out the overlooked merits of a little known adrenocortical
hormone called pregnenolone. Dr. Edward Henderson and his asso-
ciates recognized that pregnenolone appears to possess certain
advantages over other steroid compounds and should be further
investigated. They were impressed with its low toxicity and lack of
adverse side effects and, even at that point, had already discovered its
potential as a treatment for rheumatoid arthritis.’

PREGNENOLONE INHIBITORS

AGE
Our ability to produce pregnenolone, as well as most other hor-
mones, declines with age. In fact, recent studies are beginning to
find fascinating correlations between diminishing levels of hormones
like DHEA and age-related disorders of all types, including the pre-
disposition to become heavier with age. Since the dawn of time, the
quest for sustaining youth has been pursued. Today, scientists are just
beginning to understand the physiological mechanisms which set
12 PREGNENOLONE

our biological clocks. Hormonal replacement therapies have

emerged as one of the most promising tools to resist aging and the
degenerative diseases it initiates.
While the use of pregnenolone or DHEA protocols is still rela-
tively new, both substances are known to have some very significant
effects on human physiology. How and when we age is determined
to a great degree on our synthesis of hormones like preg and DHEA.
It is estimated that after the age of 75, we produce less than half the
pregnenolone we synthesized at age 35. One of the reasons our
DHEA levels drop with age is also due to the decreasing presence of
a specific enzyme required to convert pregnenolone to DHEA.

DRUGS
A number of prescription drugs can actually block the synthesis of
cholesterol, which in turn creates a pregnenolone shortage. New
studies suggest that people taking specific drugs to lower their cho-
lesterol levels may develop behavioral abnormalities or even increase
their risk of cancer because their preg production has been inadver-
tently blocked. A lack of pregnenolone can also cause impaired brain
function, possibly leading to mood disorders or even suicide. Two of
these prescription drugs are Mevacor (lovastatin) and Pravachol
(provastatin). Both of these drugs reduce the cholesterol level of the
blood by preventing cholesterol formation. Consequently, hormones
synthesized from cholesterol are also negatively impacted.
The link between cholesterol-lowering drugs and mental disorders
(such as depression or violent behavior) discourages the long-term
use of such drugs and strongly supports the notion that sufficient
pregnenolone levels in the brain are crucial to the maintenance of
normal mental function. It is also possible that using this class of
drugs may decrease brain cell stores of cholesterol and other steroidal
compounds.
Scientists who are aware of this connection are now advocating
the possible use of pregnenolone supplementation in cases where
 THE ULTIMATE HORMONE PRECURSOR 13

anticholesterol drug therapy is necessary. While taking pregnenolone

in conjunction with these drugs may not totally rectify the problem,
it may help to lessen its deleterious effects on brain neurochemistry.
Note: Some professionals advocate using pregnenolone for anyone
who must take drugs which lower blood cholesterol.

THERAPEUTIC APPLICATIONS

OF PREGNENOLONE
A number of physiological conditions may be significantly affect-
ed by pregnenolone therapy. While additional research is needed,
initial studies are more than encouraging. They support the notion
that replacing supplies of certain adrenocortical hormones may help
alleviate a number of disease conditions while simultaneously poten-
tiating the immune system. Pregnenolone therapy seems to be par-
ticularly helpful for the same conditions that DHEA supplementa-
tion benefits. These are:

* autoimmune diseases * immune system weakness

¢ memory disorders
* chronic fatigue
¢ rheumatoid arthritis
* nerve trauma
* skin rejuvenation
* mood disorders
¢ hormone based disorders
© stress
* psoriasis
¢ multiple sclerosis

Diseases which may also respond to pregnenolone therapy include

scleroderma, ankylosing spondylitis, osteoarthritis, prostate disease,
osteoporosis, hypothyroidism, Parkinson's disease and seizures. Of
particular interest is the possibility that pregnenolone very subtly
supports the adrenal glands, thereby supporting the synthesis of
other steroid compounds which may fall to lower than ideal levels.°
As more research is done and more evidence surfaces concerning the
antiaging properties of both pregnenolone and DHEA, the two
14 PREGNENOLONE

compounds will more than likely be widely used to counteract age-

related degenerative processes. Several of the conditions that benefit
from preg supplementation will now be discussed in more detail.

ENHANCED BRAIN FUNCTION

At one point, scientists believed that the steroids found in brain

tissue originated from other parts of the body. In time, they discov-
ered that the brain possesses significant steroid precursor com-
pounds, including cholesterol and the enzymes required to change
cholesterol to hormones. These neurosteroids play a profound role in
brain chemistry and function, and are only now being singled out
for their contribution to neurophysiology. Pregnenolone is one of
the most important neurosteroids that has become the focus of new
research. It is the cognitive-stimulatory effect of pregnenolone that
makes it potentially valuable for specific brain disorders, especially
those which are result from aging.
Pregnenolone can effect brain functicn in a very specific way. It
acts as a GABA antagonist, which simply refers to its ability to pre-
vent certain chemicals from attaching to GABA receptors. When
GABA receptors are inhibited, sensations of relaxation or sleep are
also inhibited. (Substances like Dilantin, an anticonvulsant, Valium,
and various other sedatives are designed to attach to GABA recep-
tors.) In other words, preg interferes with chemical joining, thereby
creating a stimulatory effect. Instead of brain function slowing
down, it is stepped up.’ This effect partially explains why the facto-
ry workers engaged in piece work were able to function much faster
and more efficiently without experiencing the mental and physical
fatigue normally associated with demanding or repetitive tasks.

MEMORY

It is a well known fact that as we age, our brain cell count declines.
Consequently, neurosteroid production which takes place in brain
 THE ULTIMATE HORMONE PRECURSOR its)

tissue also diminishes. Scientists are just now beginning to appreci-

ate what results from this change in brain chemistry. Decreased lev-
els of pregnenolone and DHEA inhibit our ability to think fast and
retrieve stored information. Activities such as calculating math prob-
lems, memorizing facts and numbers, or remembering details are all
inhibited as neurosteroid synthesis declines. Today, scientists are seri-
ously looking at the promising effects of supplementing these dimin-
ishing hormones, not only to combat mental deterioration but also
to reduce the overall physiological effects of aging. While compre-
hensive studies with pregnenolone and human brain function are
lacking to date, memory enhancement has been linked to both
DHEA and preg supplementation in laboratory test animals.
In fact, a 1992 study conducted with laboratory mice concluded
that the clinical administration of pregnenolone in aging individuals
could significantly improve memory function.’ What this study
found was that low serum levels of pregnenolone in aging individu-
als contribute to memory and behavioral disorders generally associ-
ated with geriatric patients. It also pointed out that certain drugs
prescribed for cancer and mental disorders frequently block the syn-
thesis of cholesterol, thereby resulting in a deficiency of preg-
nenolone.”
In addition, a 1995 study conducted with laboratory mice record-
ed that, “fewer than 150 molecules of pregnenolone sulfate signifi-
cantly enhanced post-training memory processes . . .”'” A paper pub-
lished in the Proceedings of the National Academy of Sciences dis-
cusses the effect of pregnenolone on the learning ability of rats. The
research team concludes that very small amounts of pregnenolone
raise cognitive ability.

ALZHEIMER'S DISEASE
Just recently, the FDA approved a study of pregnenolone's effec-
tiveness in combating Alzheimer’s disease.'' Ongoing studies are
evaluating the use of pregnenolone in 500 mg dosages for patients
16 PREGNENOLONE

who are suffering from Alzheimer’s. Within a year, the results of this
study should be published and will shed much needed light on the
pharmacology, safety and neuropsychiatric applications of preg-
nenolone.
Concerning brain function, the link between pregnenolone and
DHEA production is also very relevant. Dr. C. R. Merrill of the
Laboratory of Biochemical Genetics in Bethesda, Maryland found
that individuals suffering from Alzheimer’s disease had 48 percent
less DHEA than their healthy peers. Dr. Ward Dean states in Smart
Drugs and Nutrients that DHEA protects brain cells from
Alzheimer’s disease and other senility-associated degenerative condi-
tions.

DEPRESSION

Over the last few decades the acceptance of depression as a neu-

rochemical disorder, as well as its accepted link to levels of estrogen,
progesterone and thyroxin, strongly suggests that other adrenalcorti-
co-steroids may also impact this devastating disease. While complete
and long term studies are lacking, some research does exist which
correlates low levels of pregnenolone with incidences of clinical
depression.” The thyroid gland’s connection to depression is impor-
tant, and it may also influence the way pregnenolone is produced or
converted into other steroids. The hormonal component of depres-
sive illness is an integral one and may be much more significant than
previously thought. Consider the following:

... the hypothalamus is the area in the brain that regulates and bal-
ances your body’s hormones. Like other brain tissue, it will respond
to the chemical environment of the brain, producing the necessary
hormones. In order to produce these hormones, you must supply
your body with amino acids, essential fatty acids, vitamins, and
minerals, which are ideally derived from a good, nutritious diet. If
you're depressed, you can be suffering from a lack of certain brain
chemicals. This deficiency can initiate hormonal imbalances and
 THE ULTIMATE HORMONE PRECURSOR iL7/

metabolic malfunctions. If you have a hormonal imbalance to start

with, becoming depressed may be an inevitable outcome of a disor-
dered endocrine system.”

DELTA SLEEP AND PREGNENOLONE

While we know that pregnenolone blocks GABA receptors and

interferes with the tranquilizing effects of sedatives, a study con-
ducted in 1993 found that taking one milligram 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 REM sleep, the stage during which we dream. The implications
of this effect are not yet known; however, the fact that pregnenolone
supplementation alone affects the sleep function of the brain sup-
ports its profound effect on neurochemistry in general.

STRESS

It is a well known fact 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 adrena-
lin and other related hormones. If the stress is prolonged enough, the
glands may become somewhat exhausted, resulting not only in phys-
ical fatigue, but also in conditions such as depression and suscepti-
bility to infection. The types of stress which can cause this phenom-
enon include mental strain, physical exertion, emotional shock, any
type of injury or trauma, surgery and certain diseases such as AIDS.
A series of tests in the 1940s evaluated pregnenolone’s effect as an
antifatigue agent under stressful conditions. Ketosteroids are body
compounds that serve as “stress markers” in that the higher their
excretion, the more stress the body has sustained. Using 50 mg of
pregnenolone daily resulted in a marked reduction of ketosteroid
excretion in the urine. Additional findings confirm that psychomo-
tor performance in stressful job situations such as plane piloting also
improved. Preg supplements enhanced the performance of various
18 PREGNENOLONE

labor-oriented jobs, including those of lathe workers, leather cutters

and other task oriented work. Performance was assessed on the basis
of overall productivity, quality of task performed, frequency of mis-
takes and sensations of mental and physical fatigue. The exact bio-
logical mechanism stimulated by this particular dose of pregnenolone
(50 mg) is not fully understood, but positive brain cell activity initi-
ated by pregnenolone supplementation obviously occurred.

SPINAL CorRD INJURY AND ENHANCED RECOVERY

A 1994 study found that compressive spinal cord injuries could

well benefit from pregnenolone supplementation. “A highly signifi-
cant reduction of damage was achieved by immediate post-injury
treatment with a combination of indomethacin (an anti-inflamma-
tory drug), bacterial lipopolysaccharide and pregnenolone.” This
study involved rats with traumatized spinal cords and the findings
were impressive, to say the least. The majority of the test animals
were able to function after only 21 days, as compared to their coun-
terparts who did not receive the same therapy. The combination of
pregnenolone and indomethacin seemed to actually enhance nerve
cell regeneration. This study concluded that pregnenolone supple-
mentation may play a key role in promoting recovery after spinal
cord trauma. It may also be valuable in other cases involving nerve
or tissue trauma.

AUTOIMMUNE DISEASE

Continued research testing on adrenocortico-steroids like DHEA

suggests that replacing hormones may play a beneficial role in inhibit-
ing the development of autoimmune diseases where the body actual-
ly attacks itself. Several diseases fall into this category, including forms
of arthritis and colitis, lupus, and Crohn’s disease. In addition, mul-
tiple sclerosis, some forms of diabetes and even hypertension have
been speculated to be by-products of the autoimmune phenomenon.
 THE ULTIMATE HORMONE PRECURSOR 19

MULTIPLE SCLEROSIS

The exact cause of multiple sclerosis (MS), a disease of the central

nervous system, remains unknown, but the notion that it may be the
manifestation of an autoimmune disease has merit. Simply stated,
MS involves a breakdown of the myelin sheath that surrounds nerves
located in the spinal cord. When this protective covering is eroded a
number of distressing symptoms can occur, depending on the loca-
tion of the demyelination. The cells which comprise the myelin
sheath covering of these nerves are referred to as Schwann cells. A
recent study (1992) found that Schwann cells contain significant
concentrations of DHEA and pregnenolone." This study suggests
that nerve cells, like brain cells, may actually produce both DHEA
and pregnenolone and that these hormones play an intrinsic role in
maintaining normal nerve function.
In 1990, a study was conducted involving 21 patients suffering
from MS. For several weeks they were given DHEA and though
some overall improvement was noted, definite alterations in neuro-
logical dysfunction were not observed.'” It has been proposed that
combining DHEA with pregnenolone may prove more effective in
higher doses and have less side effects. In 1995 a team of research sci-
entists subsequently discovered that progesterone is an integral com-
ponent in the physiological mechanisms required to heal damaged
nerve cells. This study found that when levels of pregnenolone and
progesterone were too low, damaged nerves failed to regenerate
myelin sheath coverings. Conversely, resupplying progesterone and
pregnenolone initiated normal myelin sheath synthesis.'* An addi-
tional study which found that thyroxin greatly influences the con-
version of pregnenolone to progesterone may also have some bearing
for MS patients.’ Their thyroxin levels should be tested.
20 PREGNENOLONE

LuPuUS
In 1951, a study using pregnenolone for patients with diagnosed
cases of lupus found marked improvement in various symptoms of
the disease.”” Among these symptoms were lessening of joint pain
and reduction of the skin rash which typically accompanies the dis-
ease. Interestingly, studies using DHEA for lupus patients yielded
similar results. Because pregnenolone very easily converts to DHEA,
its value for lupus may be underestimated. A recent open study of
DHEA for the treatment of lupus obtained some very encouraging
results. DHEA supplementation stimulated the production ofinter-
leukin-2, a critical component of the immune system which is con-
spicuously low in people suffering form lupus.’! Because the body
determines which steroidal hormones pregnenolone will be convert-
ed into, immune system disorders may well benefit from its supple-
mentation as a DHEA precursor.

RHEUMATOID ARTHRITIS

Some of the earliest tests conducted with pregnenolone dealt with

its effect on patients suffering from rheumatoid arthritis. The gener-
al consensus of these studies was that pregnenolone may be an effec-
tive supplement in contributing to the management of rheumatoid
arthritis. Mobility was enhanced, and pain and tenderness decreased.
Daily activities which normally presented an enormous problem for
arthritic individuals became realistically possible. It is important to
keep in mind that relatively high doses of pregnenolone were used in
these studies. Injections of preg produced the same type of dramatic
improvement. Researchers concluded that there was more than
enough evidence to warrant further studies exploring the value of
preg for rheumatoid arthritis.”
As is the case in incidences of osteoporosis, DHEA levels have also
been found to be lower than normal in women suffering from
rheumatoid arthritis.” This fact supports the notion that blood levels
 THE ULTIMATE HORMONE PRECURSOR al

of DHEA are able to predict bone mineral density to some extent—

a fact which suggests the possibility of DHEA or pregnenolone ther-
apy for arthritic conditions. More study is needed to fully appreciate
the potential of preg and DHEA for arthritic disease. If combining
pregnenolone with an anti-inflammatory drug greatly enhances
nerve cell healing, the same type of effect might be observed in
inflamed joints.

IMMUNE SYSTEM WEAKNESS

Once again, while research has not confirmed the value of preg-
nenolone therapy for enhanced immune function, various studies
confirm the positive role of DHEA on the immune system. Keep in
mind that DHEA can be synthesized from pregnenolone, therefore
any beneficial effect resulting from raised DHEA levels also supports
increased pregnenolone levels. A number of research teams have
found that DHEA plays a significant role in regulating the body’s
immune responses.* The hormone has been tested on herpes,
encephalitis and other infectious agents. Findings derived from these
experiments strongly suggest that DHEA can help to protect against
potentially fatal infections.”
A 1994 study oflimited scope found that both preg and DHEA
participate in certain immune system mechanisms which help to
adjust immune responses according to specific need.” Laboratory
tests conducted with the influenza virus found that these hormones
may have the ability to protect the body from certain viral infections,
even when weakened by old age. At this writing, tests seems to sug-
gest that DHEA may modify host resistance mechanisms rather than
actually inhibiting the virus. The study concludes that DHEA treat-
ment “overcame the age-related defect in the immunity of old mice
against influenza.”” Immunity weaknesses that are the result of
aging as well as the loss of lean tissue may specifically benefit from
pregnenolone replacement.
22 PREGNENOLONE

Studies strongly suggest that anyone who has poor immune

response or who is suffering from a disease like AIDS may benefit
from increased levels of DHEA—levels which are directly linked to
the availability of pregnenolone.

HORMONE REPLACEMENT THERAPY

The pros and cons of hormone replacement therapy have stirred
up significant controversy. Medical practitioners generally believe
that for most women, the advantages of hormone replacement out-
weigh any health risks that may occur with treatment. Replacing
estrogen in aging women is considered a way to decrease the devel-
opment of cardiovascular disease and osteoporosis. |
Unfortunately, synthetic hormone compounds involve the use of
pharmaceutical estrogen and progesterone, compounds which have
more than thirty negative side effects associated with their use. These
side effects include increased risk of breast tissue abnormalities and
endometrial bleeding. The risks involved with taking synthetic hor-
mones are due to their chemical structure. Altered portions of mol-
ecules resembling estrogen or progesterone convey a somewhat dif-
ferent signal to targeted cells. It is this atomic manipulation which
can cause a number of harmful reactions within human tissue. In
addition, medical practitioners are beginning to observe that replac-
ing estrogen and progesterone does not always produce the desired
results.
As we age, most of our hormones decrease. Considering the fact
that pregnenolone converts to DHEA and DHEA subsequently con-
verts to estrogens and androgens, a fascinating question arises.
Instead of trying to give the body synthetically derived hormonal
compounds in their final state, why not prompt the body to make
more of its natural variety. Using pregnenolone with DHEA may
accomplish this very task without incurring the kind of health risks
associated with hormone replacement therapy. Dr. Eugene Roberts
of the Beckman Research Institute in California has done much
 THE ULTIMATE HORMONE PRECURSOR 23

research on such therapy. He explains that restoring optimal

steroidal balance through the use of pregnenolone, alone or in com-
bination with much smaller dosages of other steroids, is likely to be
much less physiologically damaging than administering arbitrarily
selected amounts of more potent substances.”
Simply stated, the notion that giving the body a precursor of a
desired substance is superior to subjecting it to strong chemical
compounds is an idea profound in its implication for steroidal and
hormonal therapies. Currently, a wild yam extract called diosgenin is
being used for its rich phytoestrogen content and, like pregnenolone
and DHEA, is considered a natural precursor to the formation of
progesterone. Using wild yam to stimulate progesterone production
and thereby achieving a better balance of estrogen and progesterone
has been pioneered by Dr. John R. Lee, M.D. He has achieved some
remarkable results by using cream forms of diosgenin on his female
patients.
The thyroid connection to the conversion of pregnenolone to
progesterone has recently been observed in research testing. This
connection supports the notion that impaired thyroid function in
women can significantly contribute to hormonal disorders such as
PMS. A study conducted in 1996 found that thyroid hormone actu-
ally induces the generation of progesterone from pregnenolone.” It
only stands to reason that women who suffer from an underactive
thyroid may also experience decreased progesterone levels because
sufficient pregnenolone stores may not convert to progesterone.
The bottom line is that hormonal replacement therapy is based on
the idea that pumping the body with strong hormonal compounds
is the only way to raise declining hormonal levels. As more research
emerges, the use of hormonal precursors to stimulate an aging
endocrine system is gaining acceptability. Pregnenolone may offer an
alternative to hormone replacement therapy or may enable an indi-
vidual to use less synthetic hormone drugs. Additional studies sup-
porting this idea are needed. Certainly, future research will focus on
hormones like pregnenolone, DHEA and melatonin in conjunction
24 PREGNENOLONE

with plant phytoestrogens like diosgenin. Their possible therapeutic

potential cannot be overlooked.

HORMONAL IMBALANCE AND PREGNENOLONE

When a woman's body experiences an imbalance of progesterone

and estrogen, a variety of premenstrual symptoms can result.
Estrogen dominance occurs when a progesterone deficiency occurs.
Pregnenolone is a precursor to progesterone through more than one
biochemical pathway. If a woman is suffering from a lack of proges-
terone, her DHEA and preg levels may also be down. Stimulating
progesterone production by enhancing preg levels may be of value.
When progesterone levels are adequate, many of the disturbing
symptoms associated with PMS and menopause are alleviated.
Men may also benefit from this hormonal action. Testosterone-
related disorders may respond to pregnenolone therapy, although clin-
ical support for this notion is lacking. We do know, however, that
prostate disease is related to the deranged production of testosterone
and closely related compounds. Pregnenolone is easily converted to
DHEA, which is the building block of testosterone. Tests using
DHEA and pregnenolone for men suffering from prostate disease have
not yet emerged, but when they do, the results should be promising

SKIN REJUVENATION
Studies using pregnenolone acetate in a topical application have
found the compound to be significantly hydrating to the skin. For
decades a well known cosmetic line has included pregnenolone in its
skin cream formula. Like DHEA, this steroid compound may have
merit for aging dermal cells.

ANTIAGING COMPOUND

The process of aging inevitably results in declining levels of both

pregnenolone and DHEA. Ample evidence already exists that replac-
 THE ULTIMATE HORMONE PRECURSOR ao

ing DHEA in men and women who are advancing in age exerts sev-
eral significant benefits. One DHEA study reached the following
conclusion: “. . .the improvement of physical and psychological well-
being in both genders and the absence of side effects constitute the
first demonstration of the novel effects of DHEA replacement in
age-advanced men and women.”*”
Most of the properties of pregnenolone deal with age-related dis-
eases. Consequently, the notion of replacing pregnenolone to help
counteract the many deteriorative diseases that result from the aging
process is an important one. Pregnenolone and DHEA levels con-
tinually decline with age. It only stands to reason that supplement-
ing these compounds back into the human body may have some
rather remarkable antiaging effects.

Is PREGNENOLONE
SUPPLEMENTATION EFFECTIVE?
Unlike some oral supplements, pregnenolone appears to pass
through the walls of the intestinal tract, effectively raising blood lev-
els of the compound. It is readily absorbed and causes a prolonged
rise in elevations of both pregnenolone and pregnenolone sulfate for
between five to ten hours if high enough doses are taken. This indi-
cates that taking pregnenolone orally is quite effective. Currently, lab
testing to determine individual pregnenolone levels is not available.

PREGNENOLONE DOSAGES
Pregnenolone has been used in various doses; however, initial
therapy should begin with relatively low doses, somewhere between
five and ten milligrams. Certain disease conditions such as active
lupus inflammation or arthritis may require substantially higher
doses. However, any dose over twenty milligrams should not be
taken without the continual monitoring ofa physician.
26 PREGNENOLONE

FORMS OF PREGNENOLONE
Pregnenolone is currently available in capsule forms and comes in
varying strengths, 100 mg capsules being the strongest. Pharmaceu-
tical preparations of pregnenolone can be prepared in any prescribed
dosage.

Is PREGNENOLONE SAFE?
Unfortunately, research studies on the long-term use of preg-
nenolone do not exist at this time. Laboratory studies using large
amounts of pregnenolone supplementation in mice produced no
toxicity or unusual symptoms. Human trials using between 25 and
75 mg of pregnenolone daily resulted in one isolated case ofa skin
rash which was alleviated when supplementation was stopped.’
Injections of pregnenolone can cause local irritation, but because it
is absorbed so effectively from the digestive tract, oral supplementa-
tion is sufficient.
No test results yet indicate that pregnenolone has any deleterious
side effects; however, because it converts to a variety of other steroid
hormones is should not be taken without the consent and supervi-
sion of a medical practitioner. Pregnenolone supplementation may
cause a rise in blood pressure, although this particular side effect has
not yet been observed. Taking large amounts or using pregnenolone
for extended periods of time is not recommended. Under these con-
ditions immune function may actually be suppressed. For these rea-
sons, pregnenolone supplementation should conducted under the
supervision of a physician.
 THE ULTIMATE HORMONE PRECURSOR PAT

CONCLUSION
While more research is needed, pregnenolone may very well be a
great therapeutic agent for a number of disorders and diseases. It is
currently available without a prescription and is considered an over-
the-counter medicine. What clinical testing we do have on preg-
nenolone more than supports its potential as a healing compound.
Hopefully, more long-term testing will be done. Unfortunately, only
a handful of physicians are aware of the benefits of both DHEA and
pregnenolone. Currently, both substances remain unpatented. The
profound link between DHEA and pregnenolone is also pertinent in
that DHEA orchestrates the entire endocrine system through a
process of enzyme activation or inhibition. In short, medical science
is just beginning to appreciate certain steroidal hormones which
have been put on the back burner for decades. Initial data is excit-
ing, but it is important to remember that until more information
emerges, pregnenolone supplementation should be supervised by a
competent health care professional.
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ENDNOTES
. Dr. Eugene Roberts, “Pregnenolone-from Selye to Alzheimer’s and a model of
the pregnenolone sulfated binding sites on the GABA receptor, BIOCHEMI-
CAL PHARMACOLOGY vol. 49:1: 1-16, 1995. See also Ray Sahelian, M.D.,
PREGNENOLONE A PRACTICAL GUIDE, (Marina Del Rey, Ca.:
Melatonin/DHEA Research Institute, 1996), 22 and Peggy Noonan, “Memory
Steroid,” OMNI, Dec. 1993. V 16 n 3, 36.
. B.J. Clark, et al., “Hormonal and developmental regulation of
the steroidogenic
acute regulatory protein,” MOLECULAR ENDOCRINOLOGY, Oct., 9
(10): 1995, 1346-55. See also N. Picard-Hagen et al., “Glucocorticoids
enhance the cholesterol side-chain cleavage activity of ovine adrenocortical
mitochondria,” JOURNAL-STEROID-BIOCHEM-MOL-BIOL, Oct., 55
(1)P1995957-65.
.G. Pincus et al., “Effects on industrial production ofthe administration ofpreg-
nenolone to factory workers,” PSYCHOSOM MED. 7: 1945, 342-46.
. Ibid.
E. Henderson et al., “Pregnenolone,” JOURNAL OF CLINICAL
ENDOCRINOLOGY, 10: 1950, 455-74.
. D.M. Stocco and B.J. Clark, “Role of the steroidogenic acute regulatory pro-
tein (Star) in steroidogenesis,” BIOCHEM-PHARMACOL, Feb. 9, 51 (3):
1996, 197-205. See also M. Majewska et al., “Neurosteroid pregnenolone sul-
fate antagonizes electrophysiological responses to GABA in neurons,” NEU-
ROSCIENCE LETTERS, 90: 1990, 279-84 and Sahelian 9.
. C.A. Hauser et al., “Allopregnenolone acts as an inhibitory modulatory on
alpha-1 and alpha -6 containing GABA receptors, BIOCHEM-BIOPHYS-
RES-COMMUN, Feb. 15, 219 (2): 1996, 531-36.
.M. Wilkinson, et al., “Modulation of cardiac M2 muscarinic receptor binding
by progesterone-related steroids,” JOUR MOL CELL CARDIOL, Sept., 27
(9}2 1995, .1831-39.
9: Ibid.
10. J.R Flood et al., “Pregnenolone sulfate enhances post-training memory
processes when injected in very low doses into limbic system structures: the
amygdala is by fat the most sensitive,” PROC NATL ACAD SCI USA, Nove.
7, 92 (23): 1995, 10806-10.
11. R.L. Isaacson, et al., “The effect of pregnenolone sulfate and ethylsterol on
30 PREGNENOLONE

retention of a passive avoidance task,” BRAIN RES, Aug. 14, 689 (1): 1995,
79-84.
12. M. George, et al., “CSF neuroactive steroids in affective disorders: preg-
nenolone, progesterone, and DBI,” BIOL PSYCH, 35 (10): 1994, 775-80. See
also V. Prasad et al., “Precursors of the neurosteroids,” PROCEEDINGS OF
THE NATIONAL ACADEMY OF SCIENCES OF THE oe STATES
OF AMERICA, April 12, 1994, v 91 n8, 3220-23.
13. R. ELKINS, M.H., DEPRESSION AND NATURAL MEDICINE,
Woodland Publishing, Pleasant Grove, Utah: 1995.
14. A. Steiger, et al., “Neurosteroid pregnenolone induces sleep-EEG changes in
man compatible with inverse agonistic GABA receptor modulation,” BRAIN
RES, 615, 1993, 267-74.
15. Guth, Lloyd, et al., “Key role for pregnenolone in combination therapy that
promotes recovery after spinal cord injury,” PROCEEDING OF THE NAT
ACAD OF SCI OF USA, Dec. 6, 1994, v91, n 25, 12308-12.
16. R. Morfin et al., “Neurosteroids: pregnenolone inhuman sciatic nerves,”
PROC NATL ACAD SCI USA, 1992, 89 (15): 6790-93. See also R. Morfin
et al., “Pregnenolone and DHEA as precursors of native 7-hydroxylated
metabolites which increase the immune response in mice,” B STEROID
BIOCHEM MOL BIO 50 (1-2): 1994, 91-100.
17. Sahelian, 16. See also Roberts, 1-16.
18. H. Keonig et al., “Progesterone synthesis and myelin formation by Schwann
cells,” SCIENCE, 268 (5216), 1995, 1500-03.
19. P. Robel and E. Baulieu, “Dehydroepiandrosterone (DHEA) is a
Neurosteroid,” ANN NY ACAD SCI, Dec. 19, 1995: 774: 82-110.
20. T. McGavack, et al., “The use of pregnenolone in various clinical disorders,”
JOUR CLIN ENDOCRIN, 11: 1951, 559-577.
21. V.P. Calabrese et al., “Dehydroepiandrosterone in multiple sclerosis: positive
effects on the fatigue syndrome in a non-randomized study,” in the BIOLOG-
ICAL ROLE OF DEHYDROEPIANDROSTERONE, edited by M. Kalimi
and W. Regelson, New York: 1990, 95-100.
22. PN. Sambrook et al., “Sex hormone status and osteoporosis in post-
menopausal women with rheumatoid arthritis,” ARTHRITIS-RHEUM,
1988: 31, 973-78.
23. Sahelian, 18-19.
24. R. Morfin and G. Courchay,‘‘eeenenolone and dehydoepiandrosTERONE
as precursors ofnative 7-hydroxylated metabolites which increase the immune
response in mice,” JOUR STEROID BIOCHEM MOL BIOL, July, 1994: 50
(1-2), 91-100.
25. R.M. Loria and D.A. Padgett, “Androstendil regulates systemic resistance
 THE UTIMATE HORMONE PRECURSOR Sil

against lethal infections in mice,” ARCH-VIROL, 1992: 127 (1-4_, 103-115.

26. Morfin.
27. G. Deperola et al., “Low Dehydroepiandrosterone circulating levels in pre-
menopausal obese women with very high body mass index,” METABOLISM,
February, 1991: 40 (2), 187-90.
28. Sahelian, 13.
29. P. Robel and E. Baulieu, “ Dehydroepiandrosterone (DHEA) is a neuroactive
neurosteroid,” ANN NY ACAD ACI, Dec. 29, 1995, 774, 82-110.
30. A. Morales et al., “Effects of replacement dose of Dehydroepiandrosterone in
men and women of advancing age,” JOUR CLIN ENDOCRIN METAB,
June, 1994, 78 (6), 1360-67.
31. Sahelian, 6.

ADDITIONAL REFERENCES

S. Bruzzone and H. Lopez, “Comparative Cortical Action of Different

Pregnenolones in the Adrenalectomized Guinea Pig,” [SE,B. 48 16557. 1968.
Lambert, Lammerant and Kolanowski, “The Enhancement of Pregnenolone
Production as the main Mechanism of the prolone Stimulatory Effect of
ACTH on Cortical Production by Guinea Pig Adrenocortical Cells,” JOUR
STEROID BIOCHEM, 1984, 21 (3), 299-303.
R. Davison et al., “Effects of Pregnenolone in Rheumatoid Arthritis,” ARCHIVES
OF INTERNAL MEDICINE, 1950, 85, 975-94.
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