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 Major Depression Panic/Anxiety Disorder Substance/Alcohol Abuse Antisocial Disorder Autism Bipolar Disorder Female to Male Ratio 2:1 2:1 1:2 1:3 1:3 1:1 1:1 5:1

Schizophrenia Somatization Disorder

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 hormones. 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 synapses. 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 neurotransmission. 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 regulated. 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 medicine. 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 effects

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 replacement. 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

Acute stimulatory effect of estradiol on striatal dopamine synthesis. J

Pasqualini C, Olivier V, Guibert B, Frain O, Leviel V. Neurochem. 1995 Oct;65(4):1651-7.

Effect of a single dose of levodopa on sexual response in men and women.

Both S, Everaerd W, Laan E, Gooren L. Neuropsychopharmacology. 2005 Jan;30(1):173-83.

Effects of manipulating serotonin on the incidence of ovulation in the rat.

Coen CW, Franklin M, Laynes RW, MacKinnon PC. J Endocrinol. 1980 Nov;87(2):195-201.

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

J Clin Endocrinol Metab. 2001 Aug;86(8):3545-54. Klerman GL, Weissman MM. Increasing 1989 Apr 21;261(15):2229-35. Review.

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Low testosterone levels predict incident depressive illness in older men: effects of age and medical morbidity. J Clin Psychiatry. 2005
Shores MM, Moceri VM, Sloan KL, Matsumoto AM, Kivlahan DR. Jan;66(1):7-14.

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

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

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

Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat.

Holschneider DP, Kumazawa T, Chen K, Shih JC. 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. disorders. Expert Opin

Women's issues in mood

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 therapies. 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 symptoms.

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 symptoms. 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 followup question becomes, what are the differences between susceptible and symptomresistant 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

Hormone

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 worse. 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 wan Amino Acid Therapy treatments. Patient: Female Age: 41 Primary Symptoms: Hot Flashes, Anxiety, Depression Medications: none Tests: Neurotransmitters (urine) and hormones (saliva)

Te This table displays Neurotransmitter & Hormone test results of a patient undergoing a TAAT program.

Neurotr

Neurotransmitters & Hormones Estradiol Estrone Progesterone

Testosterone Epinephrine Norepinephrine Dopamine Serotonin GABA Glutamate PEA Histamine

After the baseline test, the patient began taking the following Targeted Amino Acid products. Products: TravaCor: EndoPlus:

contains: taurine, N-ac

contains: theani

ExcitaCor:

contains: histidin acetylcysteine, M

Dosing:
TravaCor: EndoPlus:

4 capsules daily (2 in

8 sprays (5.6 ml) daily

After two weeks the dosing was adjusted to the following and then maintained for 10 weeks and then the seco Dosing: TravaCor: ExcitaCor:

4 capsules daily (1 i

2 capsules daily (2 i

Review of Patient's Neurotransmitter tests.

Serotonin 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 increas to 39.3 in the second test.) This is likely due to the regulatory effect that serotonin exerts over norepinephrine

Glutamate 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

Norepinephrine 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.

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

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

Histamine 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. Conclusion

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 followup neurotransmitter test report symptom reduction from NeuroScience Inc. products.

Changing hormone levels can cause PMS and Menopause symptoms 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 nonhormonal treatments for hot flashes. Clin J Oncol Nurs. 2004
Barton D, Loprinzi CL. Feb;8(1):39-42. Review.

Hormones and mood: from menarche to menopause and beyond. J Affect Disord. 2003 Mar;74(1):67-83.
Steiner M, Dunn E, Born L. Review.

Luteal phase administration of agents for the treatment of premenstrual dysphoric disorder.
Freeman EW. CNS Drugs. 2004;18(7):453-68. Review. Freedman RR. Pathophysiology and treatment of flashes. Semin Reprod Med. 2005 May;23(2):117-25.

menopausal hot

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. Luteal phase ovarian steroids, stress arousal, premenses perceived stress, and premenstrual symptoms. Res Nurs Health. 1998
Woods NF, Lentz MJ, Mitchell ES, Shaver J, Heitkemper M. Apr;21(2):129-42.

A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria.

Steinberg S, Annable L, Young SN, Liyanage N. Biol Psychiatry. 1999 Feb 1;45(3):313-20.