Abdul R. Khan, MD LABORATORY DIRECTOR S. Pioneer Blvd Artesia, CA Tel: Fax: LABORATORY REPORT

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Patient Info: Name: DOB: Gender: Phone No: Collection Date: Received Date: Report Date: Age: Abdul R. Khan, MD LABORATORY DIRECTOR 18173 S.

1 Patient Info: Name: DOB: Gender: Phone No: Collection Date: Received Date: Report Date: Age: Abdul R. Khan, MD LABORATORY DIRECTOR S. Pioneer Blvd Artesia, CA Tel: Fax: Client ID: Accession No: LABORATORY REPORT Hormone Test In Range Elevated / Low Units Reference Range Cortisol Morning ng/ml ng/ml Cortisol Afternoon 0.77 ng/ml ng/ml Cortisol Evening 0.84 ng/ml ng/ml Cortisol Night 1.76 H ng/ml ng/ml IL Beta pg/ml ug/ml SIgA ug/ml ug/ml ἀ Amylase U/ml U/ml Progesterone pg/ml pg/ml Premenopausal Luteal pg/ml Premenopausal Follicular pg/mlpostmenopausal pg/ml Premenopausal Luteal Estradiol pg/ml pg/ml Premenopausal Follicular pg/mlpostmenopausal optimal when E Ratio Pg/E2 pg/ml pg/ml pg/ml Male DHEA pg/ml pg/ml Female The Performance characteristic of this assay is determined by Bioanalysis Diagnostic Laboratories. (BDL) BDL Laboratory Pioneer Blvd Ste K. Artesia, CA Abdul Rab Khan MD Laboratory Director Tel: Fax: The FDA has determined that such approval and clearance is not necessary. This test is for investigational purposes only. CLIA Lic #: 05D

2 7 6 Diurnal Cortisol 5 ng/ml Patient Hormone Level Low Elevated Average Time of Day (Hour)

3 Commentary Commentary is provided for educational purposes only and should not be interpreted as diagnostic or treatment recommendations. The NeuroEndoMetabolic (NEM) Stress Response Our body s overall approach to stress regulation is through the neuroendometabolic (NEM) stress response apparatus. There are two major components to this. A conventional neuroendocrine component, and a functional metabolic component. Only by combining the two halves can a holistic view of the body's stress response be seen and evaluated comprehensively. By incorporating the metabolism component which is systemic in nature into the traditional neuroendocrine stress response equation, which is mostly organ specific, we see how the body uses both localized organ specific responses as well as systemic responses to overcome stress from a functional perspective.the two components are organizationally broken down into six circuits each in the body: hormone, cardionomic, euroaffect, metabolism, detoxification, and inflammation. All of these six circuits work in unison to handle stress. Laboratory tests and advanced markers that can help us evaluate the NEM stress response include the following: Secretory IgA ( SlgA) When certain pathogens, e.g. fungus, bacteria or viruses, enter your body, the immediate immune response is the production of antibodies. These antibodies are known as secretory IgA (SIgA). They attach to any pathogens invading the body to destroy them. These are found in mucosal membrane, e.g. ears, eyes, nose, trachea, and the vagina. These passageways are usually the body s first line of defense against any pathogen. The IgA antibodies are thus critical when it comes to the protection of our vulnerable areas, such as the gut, oral cavity, and lungs from invading foreign substances as it prevents them from both adhering to and penetrating the epithelial mucosa present in those areas. The SIgA rhythm is diurnal in nature. This means it is at its highest during the mornings and progressively lowers towards the evening. Between ten to fifteen percent of our body s antibodies are IgA antibodies, although a very small percentage of people are not able to make them. It is believed that SIgA inhibits your inflammatory processes that cause damage to the mucosa. It may also cause an immune response which is specific to particular antigens in response to non-inflammatory processes.

4 Recent research shows that SIgA has an effect on the immunity of the mucosal excretions as well as your body s intestinal balance. Certain processes have been identified that indicate SIgA can decrease your body s inflammatory response with regards to the presence of bad bacteria and antigens that could cause allergic reactions. When your body experiences chronic stress, your body s fight or flight mode results in less SIgA production. This means your immune system becomes compromised and your body s natural defense is downgraded.chronic stress may also suppress your body s SIgA production due to elevated cortisol levels. Research on SIgA is helpful when it comes to determining your detoxifying and inflammatory circuits associated with the NEM stress response as it may give insight as to gut health, your immune response, liver function, and gastrointestinal and extracellular systems. IL-Beta An IL-1 β is a substance released to promote inflammation when you injure yourself, have an infection, or in response to an allergic reaction. It has many functions, one of which is that of a signal that indicates something is wrong. The IL-1β cytokine is also associated with such aspects as the regulation of appetite, secretion of insulin, combating fever, the formation of bone, and the development of neurons, amongst others. The levels of this cytokine in saliva and giant fibroblastoma (GCF) changes when exposed to different types of stressors (physical or psychological), infections, inflammation, and microbes. Because of this function, it is important as a marker when it comes to our body s detoxification and the NEM stress response s circuits. It seems that when the IL-1 beta is compromised, it has a negative impact on certain pathological conditions such as leaky gut (inflammatory bowel disease), rheumatoid arthritis, sepsis, Type-1 diabetes, agerelated diseases, atherosclerosis, and leukemia. Alpha Amylase The activity of alpha Amylase is measured in your saliva. It gives an indication of stress levels, whether physical or psychological, by means of the different interactions it has with your autonomous nervous system. Some studies would suggest a correlation with the activity of your Sympathoadrenal medullary Hormonal System (AHS) axis. The alpha Amylase found in saliva also seems to be a good marker for AHS integrity. Alpha Amylase levels can be increased by taking drugs that activate the sympathetic nervous system and decreased by using a beta-blockade drug. Alpha Amylase is every useful in determining certain aspects of the NEM stress response, e.g. the cardionomic, neuroaffective, and hormonal pathways. Estrogens Estrogen plays a crucial role in female sexuality and other functions. Amongst these are included the menstrual cycle, sexual development, cognitive function, emotions, heart function, protein synthesis, and bone formation, to name but a few. There are three types of estrogen: Estrone (E1), estradiol (E2), and estriol (E3). The main estrogen hormone in premenopausal women is estradiol. Men s estrogen levels seem to be consistent, no matter their age. Of the three estrogens, estriol is the mildest and has a very brief impact. It is less antagonistic than its other two counterparts and seems to control the negative effects of the other two, i.e. estrone and estradiol. A lot of research has gone into studying the relationship between the different estrogen levels during hormone replacement therapy (HRT), pregnancy and menopause as well as susceptibility to cancer. Estrogen dominance, where your estrogen levels are at elevated levels on a relative basis but normal on an absolute basis, is a very common NEM stress response dysregulation. It results in a number of symptoms, including mood swings, breast tenderness, PMS, fibroid, endometriosis, and cramps. Elevated estrogen levels in men are usually associated with obesity, i.e. men with a higher body fat percentage, as the adipose tissue serves to transform testosterone into estradiol, one of the three types of estrogen. A study to determine the levels of sex hormones in older adults found that men and women who are older had similar levels of estradiol. Estradiol plays a role in memory, cognitive function, and mood (in women). In men, Estradiol, combined with testosterone, helps with cognitive function, and memory. Progesterone Progesterone is a precursor hormone. This means the body uses progesterone to make other hormones, such as estrogen, testosterone, DHEA, and cortisol. It plays a major role in reproduction, the menstrual cycle, and heart, brain, bone, and skin health, amongst others. It also has a significant role when it comes to mood, libido, thyroid function, and the health of the adrenal glands. Progesterone is mainly produced in the ovaries (in premenopausal women) and the adrenal cortex (of postmenopausal women).

5 Both men and women have progesterone although its full significance with regards to males is as yet unclear. People who have adrenal fatigue, i.e. their NEM stress response is compromised, often have lower levels of progesterone, resulting in an imbalance of the reproductive hormones, i.e. between estrogen and progesterone. Where the progesterone levels are low, with comparatively higher estrogen levels, it is known as estrogen dominance. This does not necessarily mean your body has higher levels of estrogen, but rather that your progesterone levels are lower than normal. The reason for this is progesterone is a precursor to cortisol, and it thus can be converted to cortisol during times of stress. This leads to an imbalance between the reproductive hormones. Common symptoms indicative of low progesterone levels include breast pain, lumps in the breasts, PMS, miscarriage during the earlier stages of pregnancy, anxiety, and uncharacteristic weight gain. Although consensus has not yet been reached as far as research is concerned, it is believed that low levels of progesterone are linked to infertility in females. Strong clinical association with first trimester miscarriage is a concern for those with advanced AFS and associated low progesterone. High progesterone have a sedative effect and can be helpful as a sleep aid. Because it is metabolized by the liver, those with sluggish or congested liver need to be careful. Fatigue, anxiety, brain fog, and paradoxical reactions may arise in such people taking progesterone. To be balanced, the progesterone to the estrogen estradiol should be within :1. This means that for every units of progesterone present, one unit of estradiol is required for balance. This ratio is very general and can vary from person to person. Testosterone Testosterone, traditionally thought of as a male hormone, is present in both sexes. This sex hormone helps with libido, plays a role in the production of a number of other hormones, while also playing a role with regards to weight loss and muscle mass. As you age, however, your testosterone levels go down. This is the case with both males and females. One of the results is a loss of bone density. Men tend to have higher testosterone levels than women. Testosterone levels, however, can fluctuate when suffering from adrenal fatigue and the corresponding NEM stress response. Because testosterone can convert to estrogen, it implies that this could play a role in fluctuations with regards to testosterone levels. Low levels of testosterone can be increased with the help of DHEA or pregnenolone as it converts to testosterone and other sex hormones. A testosterone hormone replacement is also effective. Always consult with a medical practitioner before considering any form of hormone replacement because there can be many side effects DHEA DHEA has certain specific functions in the body; it helps with the metabolization process of protein, fats, carbohydrates, regulating blood pressure, weight, immune function, and is important in the production of the sex hormones testosterone and estradiol. Together with cortisol, DHEA helps to maintain blood sugar levels. An imbalance between DHEA and cortisol and the corresponding higher or lower levels of these hormones are a cause for concern as it may lead to certain illnesses. DHEA levels are often too low in the presence of advanced stages of adrenal fatigue. It is usually because of pregnenolone, the precursor hormone, which, during an NEM stress response dysfunction is being shunted to make hormones such as cortisol deemed necessary for survival instead of those deemed not as important. Higher concentrations of DHEA are usually the result of the adrenal gland, external supplementation, or androgen dysfunction. If taking a DHEA supplement, it is suggested to stop for a day and re-evaluate the situation. Lifestyle changes, diet, and weight loss help lower DHEA levels. Always consult a healthcare professional when considering taking or making changes to your supplement use. Cortisol Cortisol role plays a major role in most of your body s functions, such as the metabolism and use of proteins, fats, and carbohydrates. It also plays a role in the body s ability to cope with the stress of either a psychological or physical nature as well as with controlling inflammation and maintaining blood sugar levels. Other biological aspects need balanced cortisol levels to function at optimal levels. These include blood pressure, nerve and brain activity, heart functionality, and the immune system. It is thus necessary to ensure cortisol levels are in balance. Your cortisol levels depend on your stage of adrenal fatigue and could either be too high or too low. It is very important not to look at the laboratory values without clinical correlation. A single snapshot often can be very confusing and in fact can be misleading.

Therapeutic Cohort Results

Patient: SAMPLE PATIENT DOB: Sex: MRN: Menopause Plus - Salivary Profile Therapeutic Cohort Results Hormone Average Result QUINTILE DISTRIBUTION 1st 2nd 3rd 4th 5th Therapeutic Range* Estradiol (E2) 8.7