Hormones _ neurotransmitters

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Hormones _ neurotransmitters Powered By Docstoc
					The incidence of psychiatric disorders like depression, mania, bipolar
disorder, anxiety, obsessive compulsive disorders, and panic disorders
is different between men and women. This observation has led to
significant speculation and study regarding the role of hormones in
either increasing or decreasing the likelihood of these disorders.
Current findings, support the role of hormones as determinants in
brain function and therefore further implicate male and female
hormones as active participants in brain function. These findings also
report the reciprocal nature of the neurotransmitter hormone
interaction and point not only to the ability of hormones to affect
neurotransmitters, but also to the ability of neurotransmitters and
neuroactive therapies to affect hormones.

      A number of retrospective studies examining the gender
      prevalence of various psychiatric disorders have been published
      and their similar conclusions clearly demonstrate the existence
      of significant gender related differences for some
      neurotransmitter-related disorders. A brief summary of these
      studies is provided in the table below.

                                 Rates of Psychiatric Illness
              Disorder                            Female to Male Ratio
              Major Depression                                  2:1
              Panic/Anxiety Disorder                            2:1
              Substance/Alcohol Abuse                           1:2
              Antisocial Disorder                               1:3
              Autism                                            1:3
              Bipolar Disorder                                  1:1
              Schizophrenia                                     1:1
              Somatization Disorder                             5:1

      What may be most surprising about these findings is not that
      hormones do play a role in some mood disorders, but why do
      some disorders seem unaffected. Depression for example, is
      about two times more prevalent in women, substance abuse
      three times more common in men, while men and women are
      equally affected by bipolar disorder and schizophrenia. Most
      likely, the multiple factors that affect the nature of these
      disorders are alternately affected by hormones and in some
situations these factors cancel each other out, creating an
apparently neutral gender bias. It may also be possible that
while many factors relating to proper neurotransmission are
affected by hormones, the disturbances in disorders which have
no apparent gender bias are not affected by hormones.

While these studies were examining overall differences between
genders, more specific studies have looked at age of onset for
various disorders and have found that a number of life-stages
that are associated with changes in hormone levels are also
associated with changes in mood and neurotransmitter-related
symptoms. Puberty, for example, is associated with the
beginning of gender influence in psychiatric disorders. Here
again the differences in part are attributed to the influence of

In addition to the differences in the incidence of some
psychiatric disorders between men and women, a number of
hormonally significant life events including puberty, childbirth,
menopause, menstruation, hormonal contraception, and
hormone replacement, have also been shown to correspond to
changes in the incidence and onset of psychiatric disorders.
These life events or therapies, are associated with significant
changes in hormone levels, and add significantly to the amount
of information available regarding the ability of hormone levels
to influence psychiatric disorders. Traditionally, the changes in
mood and behavior associated with these life events have been
considered to be exclusively hormone-related. However,
neuroendocrine studies during these stages has greatly
expanded the role of hormones beyond traditional reproduction,
masculinization/feminization, and adrenal issues to include
cognition and proper mental function as well.

Hormones affect the brain in many ways. Neurons themselves
have surface receptors for hormones, that directly influence
neuron depolarization. Hormones may also act upon the nucleus
and influence the production of enzymes and proteins inside the
neuron. Estradiol is probably the most studied of the male and
female hormones and has many positive effects on
neurotransmission. Other hormones have inhibitory or mixed
roles and many are are less well characterized regarding their
effects on neurotransmission.
The role of estrogen (estradiol) in brain function and
cognitive/affective disorders has been examined extensively.
Estrogen deficiency has been linked to mood disorders in
susceptible women and cognitive declines in men. Supporting
clinical evidence finds that depressed postmenopausal women
taking estrogen have lower depressive scores and possibly
receive protection from cognitive disorders like Alzheimer's and
Parkinson's. Even non-depressed postmenopausal women taking
estrogen therapy report positive mood effects with estrogen
replacement. Estrogen also has a neuroprotective role against
schizophrenia. This neuroprotective role is supported by the
observation that women have a later age of onset (they are
protected by their higher estradiol levels) than men, as well as
an increase in the number of new cases of schizophrenia
coincides with end of menstruation (estradiol levels fall and the
protection is lost).

A number of biochemical findings underlie these clinically
observed effects. Estradiol increases the synthesis of serotonin,
and it has been shown to inhibit the MAO (monoamine oxidase)
mediated degradation of neurotransmitters, as such estradiol
may work like a mild antidepressant by increasing serotonin as
well as other neurotransmitter levels. There are also estradiol
receptors on neurons that increase neurotransmission to
improve neuron communication and neuroadaptive (learning)
processes, including Long Term Potentiation (LTP)and memory
formation. Surface receptors for estradiol may also include IGF-1
receptors which have been implicated in the protective role of
estradiol in Parkinson's. Estradiol also acts as a serotonin
agonist thereby stimulating the serotonin receptor directly and
as such has a serotonin-like effect on its own. Additional positive
effects of estrogen may be due to the observation that estradiol
stimulates a significant increase in the serotonin receptor sites
(5HT2a) which are involved in both mood and cognitive function.
Yet another method by which estrogen improves brain function
is via the production of Brain Derived Growth Factor (BDNF) a
factor which stimulates neurons to grow and develop new

Some indirect neural protective actions include estrogen's ability
to act as an antioxidant, reduce the inflammatory response,
increase the growth of acetylcholine neurons, inhibit ApoE,
increase adrenal glucocorticoid production, and increase cerebral
blood flow.

Other hormones are more mixed in their effects on
neurotransmission. Cortisol, DHEA, testosterone, and
progesterone all enhance MAO (monoamine oxidase) enzymes
and therefore speed the catabolism or break-down of
neurotransmitters and reduce neurotransmission. As
mentioned, the findings regarding these hormones are mixed
because in addition to increasing the degradation of
neurotransmitters, which reduces neurotransmission, they also
have other neuroactive functions, which increase

Progesterone is mildly sedating for many patients. This is
believed to be due to its ability to increase the synthesis of the
GABA enhancing neurosteroid, allopregnanolone. This positive
calming observation is tempered by the observation that adding
progesterone to an estrogen only hormone replacement
program negates the positive mood effects of estrogen
replacement. This may be due to reduced norepinephrine and
serotonin values caused by increased MAO.

DHEA can be stimulating and in some cases can increase
anxiety. This in part may be due to its ability to upregulate MAO
as well as its function as a negative regulator of GABA function.

Testosterone can have a negative effects on neurotransmission
by decreasing neurotransmitter levels via the upregulation of
MAO (monoamine oxidase). However, testosterone also has a
positive role in affecting norepinephrine neurons. This is
supported by studies that have found that the norepinephrine
acting antidepressants were less effective in the absence of
testosterone. Serotonin acting antidepressants were not
affected by low testosterone levels.

Cortisol receptors exist on almost every cell in the body and
have an important role in brain function. Cortisol may cause
fatigue by depleting serotonn (5-HT) in the raphe nuclei, the
area of the brain that normally activates the release of NE to
increase vigilance. Moderate and transient amounts of cortisol
increase the release of dopamine from this pleasure pathway as
part of the reward cascade. High and chronic levels of cortisol
decrease the production and release of dopamine – thus
feelings of pleasure can be harder to produce. In this aspect
stress can be a factor in depressive symptoms if either the
levels of cortisol are too high or too low. Cortisol is the
precursor to the anxiety reducing (anxiolytic) and GABA
potentiating neurosteroid, 4-deoxycorticosterone. Cortisol also
upregulates tyrosine hydroxylase, the rate limiting enzyme in
the synthesis of catecholamines. Cortisol can also increase the
transcription of PMNT phenyl-N-methyltransferase, the enzyme
responsible for converting norepinephrine to epinephrine. As
previously mentioned the upregulation of neurotransmitter
function is tempered because cortisol also increases MAO
(monoamine oxidase).

Just as hormones affect neurotransmitters, neurotransmitters
affect hormones. This area of research has not been fully
explored, but a number of biochemical and clinical observations
point to the close interactions between the neurotransmitter and
hormone related systems, especially serotonin and dopamine.
One of the most frequent clinical observations regarding the
interaction of neurotransmitters and hormones is the
development of sexual side-effects with serotonin acting
antidepressants. It is estimated that as many as 70% of patients
taking SSRIs experience sexual side-effects. This stands in
contrast to the general view that sexual behavior is hormonally

Serotonin and serotonin acting drugs may cause sexual side
effects via the 5HT1 serotonin receptor, which is well studied for
its ability to inhibit sexual response. The serotonin receptor
5HT2, in contrast, enhances sexual function, but it is the 5HT1
receptor that is a target for many antidepressants. Another
aspect, is that serotonin affects the production of hormones.

Neurotransmitters, as well as medications that interact with
neurotransmitter receptors, can increase the the production of
hormones. A commonly reported finding is that serotonin can
increase the synthesis of hormones from the anterior pituitary.
Relevant to sexual dysfunction, serotonin increases prolactin
levels. Prolactin in turn decreases testosterone levels. Here
again, this finding is tempered by the fact that serotonin also
increases luteinizing hormone (LH), and luteinizing hormone
increases the production of testosterone in men and estradiol in
women. In contrast to the effects of serotonin, dopamine
decreases prolactin and dopamine acting medications are
currently used to reduce the suppressive effects of prolactin and
increase testosterone. Dopamine also has been found to
stimulate the increase of human growth hormone (hGH). This
finding has gained some public awareness due to possible effects
on insulin like growth factor (IGF-1) and adherents to anti-aging

Serotonin also increases Adrenocorticotropin hormone (ACTH).
ACTH stimulates the adrenal gland to increase the production
and release of cortisol. This enhancement of the adrenal
response provides a possible mechanism by which serotonin
enhancement can help with stress adaptation and coping.

Hormone deficiencies and imbalances are associated with
significant clinical symptoms as well as mood and behavioral
changes and hormone replacement has been shown to
positively affect quality of life. The hormones used in hormone
replacement therapy, including: estrogen, progesterone, and
testosterone, significantly affect a number of neurotransmitters.
This finding suggests that the effect of hormones on
neurotransmitters is an important part of their therapeutic
action. However, the possible health risks associated with
hormone containing therapies have created considerable
reluctance regarding the use of hormone replacement therapies.
Because of these concerns, increasing numbers of patients are
being treated with neurotransmitter-active therapies for
hormone-related mood changes or symptoms.

Neurotransmitter therapies are being used to treat:

      PMS (Premenstrual Syndrome)
      Post-Partum Depression
      Depression due to oral contraceptives
      Adolescent mood swings and aggression
      Stress related anxiety and depression
     Menopause related mood and memory changes

Given the health concerns associated with HRT, nonhormonal
therapies provide an attractive option to minimize neurological
symptoms associated with hormone changes while eliminating
or reducing the doses of hormone containing therapies.

Non-hormonal therapies may also provide specific advantages
in populations where hormone containing therapies may carry
increased health risk.

This includes children.
Due to the ongoing neural development and the incomplete
maturation of the brain during childhood and adolescence,
behavioral therapies are recommended as a first line of
treatment followed by nonprescription and prescription
neurotransmitter acting therapies.

This includes pregnant women and nursing mothers.
While many hold the opinion that all therapies should be
avoided during pregnancy and lactation, it has been shown that
neurochemical imbalances present in women during pregnancy
are passed on to their children. Failure to treat must also be
recognized as a risk factor for neonates.

This includes patients taking hormonal contraception.
Non-hormonal therapies are much less likely than hormonal
therapies to alter the effectiveness of contraception.

NeuroScience has received feedback from physicians that use
TAAT (Targeted Amino Acid Therapy) products as well as
hormone containing therapies with their patients. These reports
confirm the many observations that neurotransmitter-related
therapies can reduce hormonal symptoms. It is our feeling that
adequate neurotransmitter levels provide a level of resistance to
the development of symptoms caused by hormonal deficiencies
or hormonal fluctuations. Targeted Amino Acid Therapy
products provide a nonhormonal approach that avoids the
health concerns associated with hormone therapies. If
symptoms cannot be managed with TAAT alone, the
neurotransmitter support it provides can reduce the level of
hormone doses required to eliminate symptoms.

The following table provides a summary of observations
reported to NeuroScience by physicians using NeuroScience
Targeted Amino Acid Therapy with their patients.

             Reported Uses of NeuroScience TAAT Products
       Premenstrual (PMS)symptoms can be managed
       Perimenopause symptoms can be managed
       Sex hormone doses can often be decreased
       Patients on L-Thyroxine may require lower doses
       Patients on Cortef may tolerate lower doses without side

Given that there are clear differences between the sexes and
definitive connections between neurotransmitter and hormone
related symptoms, the next question and the one that is most
relevant to patient treatment is how can this information be
used to better assess or better treat patients with
neuroendocrine symptoms? This complex interaction provides
many layers of checks and balances that work together to keep
the neuroendocrine systems functioning. Understanding these
interactions, can improve and tailor interventions when part of
the system fails. Using neurotransmitter and
hormone testing and neurotransmitter active therapies in
place of, or along with reduced hormone dosages can overcome
many of the symptoms traditionally attributed to hormone
imbalances, while avoiding the risks associated with hormone

This topic will be continued in the next NeuroScience Technical
Bulletin, when we expand on the clinical application of
neurotransmitter therapies for hormone-related symptoms.

     Hormones affect neurotransmitters and mood
     Estradiol decreases MAO and enhances neurotransmission
     MAO levels are increased by testosterone, progesterone,
         cortisol, and DHEA
        TAAT can manage PMS and menopausal symptoms
        Optimal neurotransmitter function provides resistance to
         symptoms of hormone imbalance and deficiencies

Pasqualini C, Olivier V, Guibert B, Frain O, Leviel V.
stimulatory effect of estradiol on striatal dopamine synthesis. J
Neurochem. 1995 Oct;65(4):1651-7.

                                  Effect of a single dose of
Both S, Everaerd W, Laan E, Gooren L.
levodopa on sexual response in men and women.
Neuropsychopharmacology. 2005 Jan;30(1):173-83.

Coen CW, Franklin M, Laynes RW, MacKinnon PC.Effects of
manipulating serotonin on the incidence of ovulation in the rat.
J Endocrinol. 1980 Nov;87(2):195-201.

Quesada A, Micevych PE.Estrogen interacts with the IGF-1
system to protect nigrostriatal dopamine and maintain motoric
behavior after 6-hydroxdopamine lesions.

Cleare AJ, Miell J, Heap E, Sookdeo S, Young L, Malhi GS, O'Keane
V. Hypothalamo-pituitary-adrenal axis dysfunction in chronic
fatigue syndrome, and the effects of low-dose hydrocortisone
J Clin Endocrinol Metab. 2001 Aug;86(8):3545-54.

Klerman GL, Weissman MM. Increasing       rates of depression. JAMA.
1989 Apr 21;261(15):2229-35. Review.

Shores MM, Moceri VM, Sloan KL, Matsumoto AM, Kivlahan DR.    Low
testosterone levels predict incident depressive illness in older
men: effects of age and medical morbidity. J Clin Psychiatry. 2005

          Progestogens used in menopause. Side effects,
Sherwin BB.
mood and quality of life. J Reprod Med. 1999 Feb;44(2 Suppl):227-32.

Banasr M, Hery M, Brezun JM, Daszuta A.  Serotonin mediates
oestrogen stimulation of cell proliferation in the adult dentate
         gyrus. Eur J Neurosci. 2001 Nov;14(9):1417-24.

         Papenfuss F, Bodis J, Tinneberg HR, Schwarz H.    The modulatory
         effect of catecholamines on gonadotropin-stimulated granulosa
         cell steroid secretion. Arch Gynecol Obstet. 1993;253(2):97-102.

         Holschneider DP, Kumazawa T, Chen K, Shih JC.
         effects of estrogen on monoamine oxidase A and B in the rat.
         Life Sci. 1998;63(3):155-60.

         Joyce PR, Fergusson DM, Woollard G, Abbott RM, Horwood LJ, Upton
         J. Urinary catecholamines and plasma hormones predict mood
         state in rapid cycling bipolar affective disorder. J Affect Disord.
         1995 Apr 4;33(4):233-43.

         Knegtering H, van der Moolen AE, Castelein S, Kluiter H, van den
         Bosch RJ. What are the effects of antipsychotics on sexual
         dysfunctions and endocrine functioning? Psychoneuroendocrinology.
         2003 Apr;28 Suppl 2:109-23. Review.

         Goodnick PJ, Chaudry T, Artadi J, Arcey S.                Women's issues in mood
         disorders. Expert Opin

To summarize, the nineteenth Technical Bulletin discussed the significant interaction between
hormones and neurotransmitters, and this is apparent in the influence gender has on the
incidence and severity of some neurological disorders. For example, addiction disorders are more
common in men, while depressive disorders are more common in women. We also covered the
effects hormones have on neurotransmission including the positive effects of estradiol on neurons
and their function, as well as the hormones testosterone, progesterone, cortisol, and DHEA,
which have both supporting and inhibiting effects on neurons and neurotransmission.

Neurotransmitters can directly affect the production of hormones and hormones can directly affect
the production of neurotransmitters. Due to this close interaction, there is significant overlap in the
clinical symptoms that are caused by either neurotransmitter or hormone imbalances. Likewise,
there is significant opportunity to take advantage of this close interaction in patient treatment.
Specifically, neurotransmitter-acting therapies are currently being used to treat symptoms related
to both Premenstrual Syndrome (PMS) and menopause even though these are health conditions
caused by changing hormone levels.

         Neuroactive therapies are being used more and more frequently for the treatment of
         hormone-related symptoms. Hormone replacement therapy has fallen out of favor in
         large part because of the findings of the 2002 Women's Health Initiative (WHI) study.
         While it is generally accepted that hormone replacement therapy (HRT) can increase
         the risk of uterine and breast cancer, this clinical trial found a significantly increased the
         risk of stroke and heart disease. Even though the actual number of patients affected
         was small, the finding was surprising because many researchers expected HRT to
actually reduce the incidence of heart disease. Since this study, doctors have been
more reluctant to prescribe HRT and women have been more reluctant to take HRT

NeuroScience Inc. WHI trial comments regarding individualized bioidentical HRT over
one-size-fits-all treatment with conjugated equine estrogens (CCEs) and progestins.

In addition to patients wishing to avoid the increased stroke and heart disease risk,
women with a history of hormone sensitive cancers, like breast cancer, are not
prescribed hormone containing therapies because they may stimulate cancer growth.
Taken together, these factors have created a significant demand driven by both the
medical and the patient community for non-hormonal alternatives that can successfully
treat menopause, PMS and other symptoms caused by changing hormone
levels including hot flashes, irritability, and mood changes. A significant amount of
research has been conducted regarding the use of neurotransmitter-acting therapies to
address this need for alternatives to hormone replacement. Specifically, serotonin- and
norepinephrine-acting antidepressants and GABA-acting anticonvulsants have been
found to be effective treatments for PMS, as well as hot flashes and other menopausal

PMS and menopause occur due to natural changes in hormone levels. While natural,
these fluctuations can seriously affect life quality. Fortunately, they can also be
effectively addressed with prescription and nonprescription therapies as well as diet and
lifestyle changes. Some of the neuroendocrine issues affecting menopause and PMS
patients are listed below.

PMS by definition is limited to the time prior to the start of the menstrual cycle, but there
is very little (if any) limit to the number of symptoms it can cause. Currently, about 150
different symptoms have been associated with PMS. These include: anxiety, irritability,
depression, mood swings, fatigue, bloating, breast tenderness, food cravings,
headache, gastric/stomach upset, diarrhea, constipation, uterine cramping, backache,
acne, edema, insomnia, weight gain, heart palpitations, and altered sex-drive.
Thankfully, no one has all 150 PMS symptoms and most women have fewer than ten.
Menopause can also cause many symptoms.

Most women say that hot flashes are the most disruptive menopause symptom because
they affect their ability to work and sleep. Hot flashes consist of a feeling of heat or
warmth that can spread from the face or neck down the chest to the entire body. The
nighttime sleep disturbances that commonly occur in premenopause and menopause
add an additional burden to the hot flashes that disrupt the patient's routine during the
day. This combination of disrupted days and disrupted nights can set the stage for a
vicious cycle of fatigue and stress.

As such, hot flashes are almost always accompanied by changes in emotional
perception and mood that can include embarrassment, distress, panic, irritation, and
annoyance. Hot flashes can also demand behavioral changes such as different clothing,
the need to go outdoors (get some cool air), an interruption of work activities, and
interrupted sleep.

When these symptoms are very mild, healthcare providers may suggest changes in
lifestyle including loose fitting clothing, exercise, stress management, deep breathing,
relaxation techniques, etc. While this may be effective for the most minor symptoms,
these types of suggestions are often laughed at by women with moderate or severe

The nature and severity of the symptoms caused by changing hormone levels, like
symptoms resulting from any cause, must be matched to the type of treatments that are
going to be used. Patient symptom diaries can help in determining the frequency and
severity of symptoms and the degree to which these symptoms are interfering with sleep
work and other daily activities. They also provide a reliable means of monitoring patient
progress and more subtle improvements in symptom frequency and severity.
(click to submit your own hot flash or PMS story.)

In many ways menopause symptoms and PMS are similar including the presence of
hormonal triggers and the presence of wide-ranging mood swings. They are also similar
in that neurotransmitter therapies are effective in their treatment. While the underlying
mechanism in PMS and menopause is not clearly known, it is generally agreed that
normal changes in hormone levels during PMS and the overall hormone decline in
menopause, can cause significant symptoms in susceptible individuals. The real follow-
up question becomes, what are the differences between susceptible and symptom-
resistant individuals? The following factors have all been considered in this regard.

A number of studies point to the role of serotonin as a factor involved in the
development of PMS and menopausal symptoms. Biochemically, patients with PMS
symptoms have lower peripheral serotonin (blood, platelet, and urine) levels during the
luteal phase than normal controls. These findings are similar to observations made in
women with menopause symptoms. Symptoms for both conditions are successfully
treated with serotonin acting medications (e.g. SSRIs). Likewise, a clinical trial using the
serotonin precursor tryptophan found a significantly greater reduction in PMS symptoms
than the placebo control group.

Further evidence that serotonin function contributes to a woman's susceptibility to PMS
symptoms comes from drug challenge tests. These tests have found that medications
that mimic the effects of serotonin alleviate symptoms, while medications that block the
actions of serotonin can cause symptoms to reoccur in treated patients. Similarly,
temporarily lowering serotonin with tryptophan depletion protocols have been able to
induce symptoms in susceptible women.

Since hormone tests were not performed on these patients, it is unknown whether the
serotonin action in these studies directly reduces symptoms or whether serotonin acts
indirectly via its effects on the production of cortisol or luteinizing hormone.

Norepinephrine is a neurotransmitter required by neurons in the brain for proper mood
regulation as well as a neurotransmitter in neurons in the body that carry signals from the
brain to the various organs, like the heart. Blood and urine testing for the
neurotransmitter norepinephrine have found patients that suffer from PMS have lower
levels than control women who did not have PMS. Studies have also found that luteal
progesterone levels are higher in PMS patients than controls. While at first these findings
may not seem related, the lower levels of norepinephrine, as well as serotonin for that
matter, may be due to increased neurotransmitter inactivation caused by the higher
progesterone values.

                    Hormones Change Neurotransmitter Levels

                                 MAO      Neurotransmitter
                                 Activity Levels

       Estradiol                     -                         +
       Progesterone                  +                         -
Progesterone can decrease neurotransmitter levels by increasing the levels of
monoamine oxidase (MAO), the enzyme that breaks down neurotransmitters. Supporting
this suggestion are findings that progesterone therapy does not relieve PMS symptoms
any better than placebo.

Progesterone is not helpful for PMS symptoms and may actually make them

Menopause studies have made a different finding. Here it is believed that higher
norepinephrine levels may contribute to a narrowing of a woman's temperature tolerance
or "thermoneutral zone." This narrowed tolerance means that small increases or
decreases in core temperature will induce hot flashes and/or chills in
symptomatic menopausal women. Studies regarding the use of SSRI antidepressants for
hot flashes have shown consistent symptom relief with SSRI antidepressants. Serotonin
appears to have an influence over norepinephrine, because even combined serotonin
and norepinephrine reuptake inhibitors (SSRI/SNRIs) like Effexor (venlafaxine) have
been found to reduce hot flashes. This indicates that serotonin may provide an overriding
or regulatory component that outweighs the drug's effects on norepinephrine. However
from these observations, it would seem that SSRIs, which lack an effect on
norepinephrine, e.g. Lexapro (escitalopram), Luvox (fluvoxamine), Zoloft (sertraline),
would be a preferred choice of therapy.

It took about 60 years for the one-size-fits-all approach to HRT to be abandoned and the
value of individualized natural hormone treatment based on testing and monitoring is
being appreciated. (Premarin was introduced in 1942.) Care must be taken to prevent
the same failed approach from being used with non-hormonal therapies and the value of
natural treatment should be examined now, not decades from now.

GABA is a player in the development of hormone related symptoms as well. GABA is
the brain's primary inhibitory neurotransmitter and acts via the ionotropic GABA receptor
to prevent overstimulation and uncontrolled neuron firing (depolarization) through tonic
inhibition of excitatory neurons. Patients with PMS symptoms may have a reduced
sensitivity of this receptor that alters ion permeability and affects many aspects of
neurotransmission. The reduced luteal GABA levels seen in PMS patients may
contribute to excitability, mood swings, irritability, and aggression.

Women that are resistant to PMS in contrast may have more efficient GABA
receptors that maintain adequate tonic inhibition even during times of lower GABA
levels. The GABA acting drug, Neurontin (gabapentin), has been found to be beneficial
in the management of both PMS and menopause symptoms (hot flashes).

GABA active drugs for PMS Possible mechanisms behind their effectiveness. Patients
that are susceptible to PMS may feel benefits from GABA supporting therapies because
GABA function itself is reduced during the luteal phase in PMS patients. Additionally, the
calming actions of GABA can directly reduce symptoms of excitability, mood swings,
irritability, and aggression.

GABA active drugs for menopause Possible mechanisms behind their effectiveness.
For patients susceptible to menopause symptoms GABA enhancing therapies may be
compensating for the reduced GABA function that occurs following the reduction
of the the GABA potentiating neurosteroid allopregnanolone. It could also be
that increased GABA function attained with GABA therapies overcomes the increase in
neurotransmission resulting from increased norepinephrine.

NeuroScience has received positive feedback from numerous healthcare providers regarding effects of the ne
products. These products contain components like 5-HTP, to support serotonin; tyrosine, phenylalanine, and
enhance GABA and reduce glutamate activity. These products also contain the vitamin and mineral cofactors

Case Study

The results expressed in this case may be unique to the individual involved. The products used
The following Case Study reviews the neurotransmitter and hormone test results of a patient that did not want
Amino Acid Therapy treatments.

Patient: Female
Age: 41
Primary Symptoms: Hot Flashes, Anxiety, Depression
Medications: none
Tests: Neurotransmitters (urine) and hormones (saliva)

                                                                   This table                       Neurotr
                                                                   Neurotransmitter     Neurotransmitters &
                                                                   & Hormone            Hormones
                                                                   test results of a    Estradiol
                                                                   patient under-       Estrone
                                                                   going a TAAT

After the baseline test, the patient began taking the following Targeted Amino Acid products.


                                                                       TravaCor:      contains: taurine, N-ac

                                                                       EndoPlus:      contains: theani
                                                                       ExcitaCor:     contains: histidin
                                                                                      acetylcysteine, M


                                                                       TravaCor:       4 capsules daily (2 in

                                                                       EndoPlus:       8 sprays (5.6 ml) dail

After two weeks the dosing was adjusted to the following and then maintained for 10 weeks and then the seco


                                                                       TravaCor:        4 capsules daily (1 i

                                                                       ExcitaCor:       2 capsules daily (2 i

Review of Patient's Neurotransmitter tests.

The neurotransmitter serotonin increased significantly following with the 5-HTP containing TravaCor. A decrea
with serotonin support is an important part of many therapies that reduce depressive symptoms. This increase
to 39.3 in the second test.) This is likely due to the regulatory effect that serotonin exerts over norepinephrine

Glutamate, which is the brain's primary excitatory neurotransmitter, is elevated at the time of the baseline test
levels are reduced at retest. This may be due to the antagonistic actions of theanine or down-regulation via in

Observations made by other researchers that norepinephrine levels are higher in patients with hot flashes is c
Note that with the Targeted Amino Acid Therapy program the norepinephrine level decreased, even in the pre
pathway for dopamine, which is subsequently a precursor to norepinephrine.

The level of dopamine, though remaining just below the Optimal Range of 125-175, increased following the ad

GABA, which is the brain's primary inhibitory neurotransmitter, is slightly elevated. GABA increases in respon
GABA is associated with calm, low-anxiety individuals and high GABA is associated with restless, high-anxiet

Epinephrine is an excitatory neurotransmitter. Levels increased modestly with the Targeted Amino Acid Thera

The neurotransmitter histamine provides stimulation to neural networks in order to maintain vigilance and acti
associated with drowsiness. This explains the drowsiness experienced with antihistamine medications. Note:
effects of histamine. In this patient, the histamine increased slightly due to l-histidine, the amino acid precurso

Phenylethylamine (PEA)
Phenylethylamine (PEA) is an excitatory neurotransmitter derived from the amino acid phenylalanine. PEA va

Review of Patient's Hormone Tests

Estradiol, estrone, progesterone, and testosterone all increased though just slig
increased enough to be at the low end of the Optimal Range.


Despite the relatively small increases in all the hormones measured, the patient
in levels of serotonin, dopamine, and epinephrine and the decreases seen in glu

It is unknown if the small increases observed in the patient's hormones contribu
suggestive of neurotransmitter level improvements and the increases in neurotr

Antidepressant and anticonvulsant therapies are considered a safer option than
small increases observed in estradiol, estrone, progesterone, and testosterone a
however the therapy of choice for cancer survivors. This points to an overall saf

Hormonal therapies remain an option for most patients with hormone-related sy
be used along with hormone replacement. So for patients that have symptoms
and therefore considered to be safer, dose is all that is needed.

Given that there are definitive connections between
neurotransmitter and hormone related symptoms, how can this
information be used to improve and tailor interventions when
either the hormone or the neurotransmitter part of this system
fails. Neurotransmitter and hormone testing provides a way
to assess aspects of the patient's neuroendocrine status. This
information may then be used to tailor non-hormonal or
reduced-hormonal therapies that avoid many of the risks
associated with high dose hormone replacement, while still
helping to overcome many of the symptoms attributed to
hormone imbalances.

A lab test that measures the levels of the hormones estradiol,
progesterone, testosterone, DHEA, and cortisol can provide
beneficial information in most patients with PMS or menopause
symptoms. Likewise, the neurotransmitters epinephrine,
norepinephrine, dopamine, serotonin, and GABA can help
identify neurotransmitters that need to be addressed.

We have found that about 90% of patients performing a follow-
up neurotransmitter test report symptom reduction from
NeuroScience Inc. products.

     Changing hormone levels can cause PMS and Menopause
     Hormone replacement therapy (HRT) can increase the risk
      of cancer, heart disease, and stroke
     A woman's susceptibility to PMS and menopause
      symptoms is affected by neurotransmitters
     Non-hormonal therapies affecting neurotransmitters can
      reduce or eliminate PMS and menopause symptoms
     Targeted Amino Acid Therapy products have been used to
      successfully manage PMS and menopausal symptoms
     Neurotransmitter and hormone testing can help identify
      neuroendocrine imbalances

                  Making sense of the evidence regarding
Barton D, Loprinzi CL.
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to menopause and beyond. J Affect Disord. 2003 Mar;74(1):67-83.

Freeman EW.  Luteal phase administration of agents for the
treatment of premenstrual dysphoric disorder.
CNS Drugs. 2004;18(7):453-68. Review.

Freedman RR. Pathophysiology and treatment of       menopausal hot
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Blum I, Lerman M, Misrachi I, Nordenberg Y, Grosskopf I, Weizman
A, Levy-Schiff R, Sulkes J, Vered Y. Lack of plasma norepinephrine
cyclicity, increased estradiol during the follicular phase, and of
progesterone and gonadotrophins at ovulation in women with
premenstrual syndrome. Neuropsychobiology. 2004;50(1):10-5.

Woods NF, Lentz MJ, Mitchell ES, Shaver J, Heitkemper M.
phase ovarian steroids, stress arousal, premenses perceived
stress, and premenstrual symptoms. Res Nurs Health. 1998

Steinberg S, Annable L, Young SN, Liyanage N. A placebo-controlled
clinical trial of L-tryptophan in premenstrual dysphoria.
Biol Psychiatry. 1999 Feb 1;45(3):313-20.

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