TEST REPORT TEST 1636 - 466 - 503 Fax: 2445 - 466 - 503 Phone

Home , Glucuronidation, Tetrahydrocortisol

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advice. Please consult your healthcare practitioner for for practitioner healthcare your consult Please advice. otherwise specified on page 1) page on specified otherwise

purposes only and are not to be construed as medical medical as construed be to not are and only purposes (Ordering Provider unless unless Provider (Ordering Laboratory Director Laboratory 8/10/2018 9:17:53 AM 9:17:53 8/10/2018

11 of 1

The above results and comments are for informational informational for are comments and results above The Alison McAllister, ND. McAllister, Alison CLIA Lic # 38D0960950 # Lic CLIA David T. Zava, Ph.D. Zava, T. David

4.5 µg/g Cr Postmenopausal Cr µg/g 4.5 - 1.5 L

T R luteal or E or luteal - Premeno 0.29 - 0.10 H 0.33 MeO E2/4 MeO - OH E2 OH - 4

T R luteal or E or luteal - Premeno 0.13 - 0.05 H 0.26 OH E1 OH - E1/4 MeO - 4

<0.04 µg/g Cr µg/g <0.04 H 0.12 MeO Estrone MeO - 4

<0.04 µg/g Cr µg/g <0.04 H 0.05 MeO Estradiol MeO - 4

T R luteal or E or luteal - Premeno 0.38 - 0.21 H 0.47 OH E1 OH - E1/2 MeO - 2

T R luteal or E or luteal - Premeno Cr µg/g 0.68 - 0.26 0.51 MeO Estrone MeO - 2

T R luteal or E or luteal - Premeno Cr µg/g 0.08 - 0.03 0.06 MeO Estradiol MeO - 2

OH E1 OH

T R luteal or E or luteal - Premeno 5.49 - 1.29 4.19

- α - E2)/16 + (E1 OH - 2

T R luteal or E or luteal - Premeno Cr µg/g 1.07 - 0.35 L 0.31 OH Estrone OH - α 16

T R 0.17 luteal or E or luteal - Premeno Cr µg/g 0.47 - 0.47 OH Estrone OH - 4

T R 0.10 luteal or E or luteal - Premeno Cr µg/g 0.18 - 0.15 OH Estradiol OH - 4

T R 0.70 luteal or E or luteal - Premeno Cr µg/g 2.54 - 1.09 OH Estrone OH - 2

T R 0.17 luteal or E or luteal - Premeno Cr µg/g 0.70 - 0.21 OH Estradiol OH - 2

>0.3 (> median value) median (> >0.3 L 0.24 E3/(E1+E2)

T R 0.78 luteal or E or luteal - Premeno Cr µg/g 1.98 - 0.83 Estriol

T R 2.27 luteal or E or luteal - Premeno Cr µg/g 5.22 - 2.85 Estrone

T R 0.78 luteal or E or luteal - Premeno Cr µg/g 1.79 - L 0.68 Estradiol

Urinary Estrogens Urinary

RANGE 07/26/18 | RESULTS NAME TEST

29.2 lb 165 Postmenopausal yrs) (58 3/4/1960

BMI eight W Status Menses DOB

Unspecified in 3 ft 5 Unspecified Female

aist W Height Menses Last Gender

555 555 5555 555 555 Number: Phone Patient

Advanced Metabolites Advanced Name: Patient

- Urine 07/26/18 22:30 07/26/18

08/05/2018

- Urine 07/26/18 19:20 07/26/18 Jim Getuwell, DO Getuwell, Jim

Report Date Report

Getuwell Clinic Getuwell - Urine 07/26/18 10:00 07/26/18

Ordering Provider: Ordering - Urine 07/26/18 08:00 07/26/18 07/31/2018

# 2018 07 01 007 U 007 01 07 2018 # Samples Collected Samples Received Samples

TEST REPORT TEST 1636 - 466 - 503 Fax: 2445 - 466 - 503 Phone:

Beaverton, OR 97008 OR Beaverton, 8605 SW Creekside Place Creekside SW 8605

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11 of 2

The above results and comments are for informational informational for are comments and results above The Alison McAllister, ND. McAllister, Alison David T. Zava, Ph.D. Zava, T. David 38D0960950 # Lic CLIA

68.9 µg/g Cr (2nd Morning) (2nd Cr µg/g 68.9 - 23.4 L 15.28 Free Cortisol Free

29.5 µg/g Cr (1st Morning) (1st Cr µg/g 29.5 - 7.8 L 1.49 Free Cortisol Free

Urinary Free Diurnal Cortisol Diurnal Free Urinary

1474 µg/g Cr Postmenopausal Cr µg/g 1474 - 551 L 530 etrahydrocortisone T

1 µg/g Cr Postmenopausal Cr µg/g 1 1 7 - 281 L 192 etrahydrocortisol T

0.7 - 0.5 H 0.91 Cortisol/Cortisone

59.61 µg/g Cr Postmenopausal Cr µg/g 59.61 - 23.32 L 13.04 otal Cortisone otal T

39.26 µg/g Cr Postmenopausal Cr µg/g 39.26 - 13.23 L 1.88 1 otal Cortisol otal T

Urinary Glucocorticoids Urinary

8.17 µg/g Cr Postmenopausal Cr µg/g 8.17 - 2.32 3.87 Androstanediol - α ,3 α 5

0.26 0.98 µg/g Cr Postmenopausal Cr µg/g 0.98 - L 0.24 DHT - 5 α

0.5 3.0 - 1.17 T - T/Epi

0.39 1.32 µg/g Cr Postmenopausal Cr µg/g 1.32 - 0.78 T - Epi estosterone

0.66 2.89 µg/g Cr Postmenopausal Cr µg/g 2.89 - 0.91 estosterone T

239 777 µg/g Cr Postmenopausal Cr µg/g 777 - L 195 Etiocholanolone

152 482 µg/g Cr Postmenopausal Cr µg/g 482 - 212 Androsterone

2.07 7.94 µg/g Cr Postmenopausal Cr µg/g 7.94 - L 1.95 Androstenedione

8.63 37.28 µg/g Cr Postmenopausal Cr µg/g 37.28 - L 6.44 DHEA

Urinary Androgens Urinary

1000 1500 (Optimal Luteal Only) Luteal (Optimal 1500 - H 1869.12 1 Pgdiol/E2

T R Pg or luteal - Premeno Cr µg/g 9.59 - 3.19 L 1.48 Corticosterone

0.69 T R Pg or luteal - Premeno Cr µg/g 2.23 - 1.72 Deoxycorticosterone

Dihydroprogesterone

T R Pg or luteal - Premeno Cr µg/g 1.62 1 - 3.93 H 15.13

- α 20

Dihydroprogesterone

T R Pg or luteal - Premeno Cr µg/g 2.03 - 0.67 H 3.29

- α 3

T R Pg or luteal - Premeno Cr µg/g 76.71 - 14.65 H 148.31 Allopregnanediol

T R Pg or luteal - Premeno Cr µg/g 14.87 - 2.23 H 35.33 Allopregnanolone

T R Pg or luteal - Premeno Cr µg/g 1609 - 465 H 8071 Pregnanediol

Urinary Progestogens Urinary

RANGE 07/26/18 | RESULTS NAME TEST

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11 of 3

nded) (1 Days Last Used) Last Days (1 nded) (compou Progesterone oral Used)125mg Last Days (1 (Pharmaceutical) (Estradiol) Divigel topical 0.5mg

Therapies

= Not applicable; 1 or more values used in this calculation is less than the detectable lim detectable the than less is calculation this in used values more or 1 applicable; Not = N/A lab. the of limit detectable the than Less =

0.3 (Night) L mg/m 2.0 - 1.80 Creatinine

0.3 (Evening) L mg/m 2.0 - H 2.49 Creatinine

0.3 (2nd morning) (2nd L mg/m 2.0 - 1.98 Creatinine

0.3 (1st morning) (1st L mg/m 2.0 - 1.23 Creatinine

0.3 2.0 mg/mL 2.0 - 1.34 Creatinine (pooled) Creatinine

Urinary Creatinine Urinary

1.1 µg/g Cr (Night) Cr µg/g 1.1 1.7 1.7 1 - L 1.03 Melatonin

0.7 0.7 2.2 µg/g Cr (Evening) Cr µg/g 2.2 - 0.85 Melatonin

7.3 7.3 31.9 µg/g Cr (2nd Morning) (2nd Cr µg/g 31.9 - L 3.39 Melatonin

18.0 18.0 40.9 µg/g Cr (1st Morning) (1st Cr µg/g 40.9 - L 7.19 Melatonin

Urinary Diurnal Melatonin MT6s Melatonin Diurnal Urinary

15.5 44.7 µg/g Cr (Night) Cr µg/g 44.7 - L 4.56 Free Cortisone Free

30.6 88.5 µg/g Cr (Evening) Cr µg/g 88.5 - L 8.68 Free Cortisone Free

175.8 µg/g Cr (2nd Morning) (2nd Cr µg/g 175.8 - 63.3 L 51.45 Free Cortisone Free

91.6 µg/g Cr (1st Morning) (1st Cr µg/g 91.6 - 31.6 L 5.27 Free Cortisone Free

Urinary Free Diurnal Cortisone Diurnal Free Urinary

8.4 µg/g Cr (Night) Cr µg/g 8.4 - 2.6 L 1.62 Free Cortisol Free

19.2 µg/g Cr (Evening) Cr µg/g 19.2 - 6.0 L 2.51 Free Cortisol Free

Urinary Free Diurnal Cortisol Diurnal Free Urinary

RANGE 07/26/18 | RESULTS NAME TEST

2018 07 01 007 U 007 01 07 2018 Results | REPORT TEST # continued

dvanced Metabolites dvanced A

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11 of 4

The above results and comments are for informational informational for are comments and results above The CLIA Lic # 38D0960950 # Lic CLIA David T. Zava, Ph.D. Zava, T. David Alison McAllister, ND. McAllister, Alison

Time of Day of Time

03:00 00:00 21:00 18:00 15:00 12:00 09:00 06:00 03:00

20 µg/g Cr

Urinary Melatonin (MT6s) Melatonin Urinary

Time of Day of Time Time of Day of Time

03:00 00:00 21:00 18:00 15:00 12:00 09:00 06:00 03:00 03:00 00:00 21:00 18:00 15:00 12:00 09:00 06:00 03:00

30 80

µg/g Cr µg/g Cr

100 40

120

140

160

180

200 80

Urinary Free Cortisone Free Urinary Cortisol Free Urinary

higher. Please see supplementation ranges and lab comments if results are higher or lower than expected. than lower or higher are results if comments lab and ranges supplementation see Please higher.

Average Off Graph Off

Graphs below represent averages for healthy individuals not using hormones. Supplementation ranges may be may ranges Supplementation hormones. using not individuals healthy for averages represent below Graphs Disclaimer:

Graphs

2018 07 01 007 U 007 01 07 2018 Results | REPORT TEST # continued

dvanced Metabolites dvanced A CLIA Lic # 38D0960950 The above results and comments are for informational David T. Zava, Ph.D. Alison McAllister, ND. 5 of 11 8/10/2018 9:17:53 AM purposes only and are not to be construed as medical Laboratory Director (Ordering Provider unless advice. Please consult your healthcare practitioner for otherwise specified on page 1) diagnosis and treatment. © 1998-2018 ZRT Laboratory, LLC. All rights reserved.

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11 of 6

Feet or Hands or Feet - Numbness Numbness

Night Sweats Night

Nervous

Nails Breaking or Brittle or Breaking Nails

Muscle Size Decreased Size Muscle

Mood Swings Mood

Memory Lapse Memory

Libido Decreased Libido

Irritable

Infertility

Incontinence

Hot Flashes Hot

Hoarseness

Heart Palpitations Heart

Hearing Loss Hearing

Headaches

Scalp Loss Scalp - Hair Hair

Increased Facial or Body or Facial Increased - Hair Hair

Dry or Brittle or Dry - Hair Hair

Goiter

Thinking Foggy

Fibromyalgia

Morning - Fatigue Fatigue

Evening - Fatigue Fatigue

Depressed

Constipation

Cholesterol High Cholesterol

Chemical Sensitivity Chemical

ender T - Breasts Breasts

Fibrocystic - Breasts Breasts

Breast Cancer Breast

Bone Loss Bone

emperature Cold emperature T Body

Blood Sugar Low Sugar Blood

Blood Pressure Low Pressure Blood

Blood Pressure High Pressure Blood

Bleeding Changes Bleeding

Anxious

Allergies

Acne

Aches and Pains and Aches

SYMPTOM CHECKLIST SYMPTOM

MILD SEVERE TE A MODER

40% Metabolic Syndrome Metabolic

30% Hypometabolism

28% High Cortisol High

29% Low Cortisol Low

11% estosterone) T (DHEA/ Androgens High

30% estosterone) T (DHEA/ Androgens Low

20% Estrogen Dominance / Progesterone Deficiency Progesterone / Dominance Estrogen

18% Estrogen / Progesterone Deficiency Progesterone / Estrogen

SYMPTOM CATEGORIES SYMPTOM RESULTS | 07/26/18 | RESULTS

.zrtlab.com/patient w symptoms. - ww to go breakdowns, category on information detailed

y ymptoms for each categor each for ymptoms s available total to ared comp patient the by reported - self symptoms of percent show below Categories Symptom Disclaimer: . For For .

2018 07 01 007 U 007 01 07 2018 Patient Reported Symptoms Reported Patient | REPORT TEST #

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11 of 7

has remained controversial and newer research suggests that while higher levels of 16 of levels higher while that suggests research newer and controversial remained has associated with associated slightly be indeed may e estron hydroxy -

ut not in postmenopausal postmenopausal in not ut b women, premenopausal in cancer breast of risk increased an with associated was ratio), E1 OH - E2/16 women. This This

OH OH - 2 + E1 OH - 2 low a (i.e. estrogens ed hydroxylat - 2 to relative hydroxyestrone - 16 of level urinary high a that suggested humans in research

clinical clinical Early Cascade). Hormone d Steroi (see estriol to precursor a is and metabolism estrone of pathway another is hydroxyestrone - 16

oxidize the catechol estrogens to quinones. to estrogens catechol the oxidize - co that (ROS) Species Oxygen Reactive of formation cause

es (1B1), and and (1B1), es enzym pathway droxylation hy - 4 induce that metals, heavy also but products based - petrochemical mostly toxins, environmental to

by exposure exposure by enhanced is metabolism en estrog hydroxylated - cance breast of prevention for therapy iodine dose higher The more dangerous 4 dangerous more The . r

196, 2008), which 2008), 196, - 189 5: Sci Med J Int et.al. FR (Stoddard hydroxylation - 4 in increase slight a with rotective e rotective p the with associated is fects of of fects f

carbinol (I3C) and its metabolite diindolylmethane (DIM). Iodine als Iodine (DIM). diindolylmethane metabolite its and (I3C) carbinol - 3 - indole of levels high contain lation of estrogens, estrogens, of lation hydroxy - 2 the increases o

s vegetables vegetables s cruciferou of extracts ed metabolism. estrogen for pathway hydroxylation - 2 safer the enhance The most commonly used concentrat used commonly most The

hydroxylated estrogen metabolism is increased with cruciferous vegetables and extracts of them, so them, of extracts and vegetables cruciferous with increased is metabolism estrogen hydroxylated - 2 ese foods will will foods ese th of consumption higher

About BREAS About our Life: Chapter 7. 7. Chapter Life: our Y Save Help Can Balance Hormone How CANCER: T

y Not y D va Za JR, Lee, and 2010; 79, - 75 6(1): Oncol Future EG Rogan EL, Cavalieri see: reviews For risk. cancer ou Y ell T Ma Doctor our Y What T

breast breast increased with associated are that mutations to leading DNA, damage and to bind which E1), OH - 4 and E2 OH - (4 hydroxyestrogens

- 4 the than on hydroxylati of pathway er saf a are E1) OH - 2 and E2 OH - (2 estrogens hydroxylated - 2 the that show studies clinical and Research

hydroxylated E1 and E2 metabolites are referred to as catechol estrogens. estrogens. catechol as to referred are metabolites E2 and E1 hydroxylated

- 4 and - 2 The below). (see groups oxyl di the of measurement hydr the of methylation to addition in estrogens, hydroxylated of types ferent f

their solubility and excretion in urine. In the laboratory these sulfate and glucuronide groups are are groups glucuronide and sulfate these laboratory the In urine. in excretion and solubility their sis, which allows for for allows which sis, hydroly enzyme by removed

tion) that increases increases that tion) glucuronida sulfation, n, (methylatio modification further undergo estrogens the position, 16 - or , - 4 , - 2 the at hydroxylation

The hydroxylation of estradiol and estrone represent the first phase of metabolism and elimination o elimination and metabolism of phase first the represent estrone and estradiol of hydroxylation The ne. Following Following ne. uri via estrogens these f

excrettion more in the bile/feces than in urine. urine. in than bile/feces the in more excrettion

estrogens from which they are derived. are they which from estrogens is likely due to to due likely is which little, very ogens opically delivered estrogens raise the level of urinary estr urinary of level the raise estrogens delivered opically T

stream hydroxylated estrogens are usually within the low end of the reference ran reference the of end low the within usually are estrogens hydroxylated stream - down the of Levels are the parent parent the are E topical with ges , as as , T R

The hydroxylated estrogens are all within/near normal reference ranges for a postmenopausal woman su woman postmenopausal a for ranges reference normal within/near all are estrogens hydroxylated The estrogen(s). estrogen(s). topical with pplementing

OH E2 & E1, 4 E1, & E2 OH - HYDROXYL OH R OH - OH/16 - 2 and E1) OH - 16 E1, & E2 OH - TECHOL) ESTROGENS (2 ESTROGENS TECHOL) A (C TED A TIO A

are more likely to be excreted in bile/feces than in urine. in than bile/feces in excreted be to likely more are

saliva and capillary blood levels of the supplemented estrogens, but increase urinary and serum leve serum and urinary increase but estrogens, supplemented the of levels blood capillary and saliva elivered hormones hormones elivered less. much ls opically d opically T

taking low dose topical estrogens (usually a topical estradiol or biestrogen containing estradiol + + estradiol containing biestrogen or estradiol topical a (usually estrogens topical dose low taking ered estrogens increase increase estrogens ered estriol). opically deliv opically T

estrogens are excreted predominately in bile and feces by this route of administration) . administration) of route this by feces and bile in predominately excreted are estrogens usal women women usal postmenopa in seen mmonly This is co is This

supplementing with topical estrogen replacement therapy (Note: transdermal and topical estrogens rai estrogens topical and transdermal (Note: therapy replacement estrogen topical with supplementing little as these these as little very estrogens urinary se

The parent estrogens are within/near the expected median to 90 percentile of the reference ranges se ranges reference the of percentile 90 to median expected the within/near are estrogens parent The n n wome postmenopausal in en

E1, ESTRIOL E1, - ESTRONE E2, - P E3) - ESTROGENS (ESTRADIOL ESTROGENS T AREN

Lab Comments Lab

aist W - eight Gain Gain eight W

Hips - eight Gain Gain eight W

ater Retention ater W

aginal Dryness aginal V

Uterine Fibroids Uterine

Urinary Urge Increased Urge Urinary

riglycerides Elevated riglycerides T

earful T

fy Eyes/Face fy f Pu or Swelling

Sweating Decreased Sweating

Sugar Cravings Sugar

Stress

Stamina Decreased Stamina

Sleep Disturbed Sleep

Thinning Skin

Rapid Heartbeat Rapid

Aging Rapid

Pulse Rate Slow Rate Pulse

SYMPTOM CHECKLIST SYMPTOM

MILD SEVERE TE A MODER

2018 07 01 007 U 007 01 07 2018 Patient Reported Symptoms Reported Patient | REPORT TEST # continued

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11 of 8

in these test these in seen as high, usually are supplementation progesterone oral from formed metabolites - Pregnane circulation. systemic the enters

ed progesterone progesterone ed deliver orally of 10% - 5 t abou Only conjugates. glucuronide as mostly urine into excreted and metabolites to rapidly converted

Approximate (allopregnanolone) in the gut lining and liver before entering the systemic circulation. systemic the entering before liver and lining gut the in (allopregnanolone) taken orally is is orally taken progesterone of 95% - 90 ly

, with exogenous oral progesterone supplementation much of the progesterone is metabolized to metabolized is progesterone the of much supplementation progesterone oral exogenous with , r Howeve etabolites etabolites m other and pregnanediol

progesterone as levels increase in parallel with endogenous progesterone production by the ovaries. ovaries. the by production progesterone endogenous with parallel in increase levels as progesterone

good surrogate marker met marker surrogate good a as serves PgDiol (PgDiol). pregnanediol elevated especially progesterone, oral of use with common abolite of the the of abolite

therapy (1965 therapy metabolites are are metabolites progesterone of levels ry urina Higher therapy). post hr 24 - 12 at progesterone oral mg 200 - 100 with Cr ug/g 7373 -

. Pregnanediol is within/near the expected re expected the within/near is Pregnanediol . y 1609 ug/g Cr with oral progesterone therap progesterone oral with Cr ug/g 1609 - (465 ranges ogesterone ogesterone pr oral for range ference

The urinary levels of the progesterone metabolites pregnanediol and allopregnanolone, a neuroactive neuroactive a allopregnanolone, and pregnanediol metabolites progesterone the of levels urinary The luteal reference reference luteal than higher are steroid,

ALLOPREGNANOLONE) (PREGNANEDIOL, ABOLITES T PROGESTERONE ME PROGESTERONE

are elevated, identification of its source and reducing exposure is worth considering. worth is exposure reducing and source its of identification elevated, are

ferent health issues, including diabetes, breast ca breast diabetes, including issues, health ferent f levels levels A P r cance prostate and , r . When B When . nce di many for risks increased with associated been

A P estr of symptoms to contribute can A P mimicking the actions of endogenous estrogens, high levels of B of levels high estrogens, endogenous of actions the mimicking levels have have levels B High dominance. ogen

mann a in receptors estrogen nuclear and membrane both activating a to binding by EDC an as acts A P B Thus by by Thus estradiol. to similar er

. . r 48 h 48 - 24

in A P B of amounts excessive released that plastics to exposure recent indicate A P urinary levels of B of levels urinary umed in the past past the in umed cons beverages or food to

is not retained in the body for a prolonged period o period prolonged a for body the in retained not is A P wraps for foods, and linings for food cans. B cans. food for linings and foods, for wraps reted into urine. High High urine. into reted exc rapidly is and time f

is an endocrine disrupting chemical (EDC) derived f derived (EDC) chemical disrupting endocrine an is A P B range. reference within is A) P (B A ing bottles, bottles, ing mak for used plastics rom Bisphenol

A) P (B A L BISPHENO

render them potentially less harmful. less potentially them render

. Even if higher levels of 4 of levels higher if Even . r hydroxylated estrone or estradiol are p are estradiol or estrone hydroxylated - cance potentially and mutations ion (higher ratio) ratio) (higher ion methylat adequate resent,

causing causing A properly are associated with increased risk for conversion to more dangerous 4 dangerous more to conversion for risk increased with associated are properly N D damage that measured) t (no quinones estrogen -

This is particularly true for the 4 the for true particularly is This range. reference the of , r towards the upper end, or highe or end, upper the towards f not methylated methylated not f i which estrogens, ylated hydrox -

good methylation methylation good A . r which renders them biochemically inert and reduces their risk for breast cance breast for risk their reduces and inert biochemically them renders which the ratio value value ratio the with associated is index

The ratios of the 4 the of ratios The methylated counterparts is evaluated to dete to evaluated is counterparts methylated - 4 their to hydroxyestrogens - ratios. ately methylated, methylated, ately adequ being they if rmine

E1) are well methylated based on the high 4 high the on based methylated well are E1) - OH - 4 and E2 - OH - (4 estrogens hydroxylated - 4 The 1 1 E - OH - E1/4 - MeO - 4 and E2 - OH - E2/4 - MeO -

TED HYDROXYESTROGENS/4 TED A 4 OF TIO A HYDROXYESTROGENS - METHYL - R

MeO - 4 the that Note risk. cancer breast lower a with associated thylation). me optimal indicates and (beneficial high is ratio E1 OH - E1/4 -

methylation of these estrogens, and consequent higher ratios of 4 of ratios higher consequent and estrogens, these of methylation be be should theoretically E2 - H O - E2/4 - MeO - 4 and/or E1 - OH - E1/4 - MeO -

estrone, and their degree of methylation of degree their and estrone, - or estradiol - 4 or - 2 formed, estrogen - hydroxyl of type The t cancer risk. Higher Higher risk. cancer t breas with associated is

is measured is A the quinone estrogens nor their interaction with DN with interaction their nor estrogens quinone the etabolites. etabolites. m methylated their and ns estroge - hydroxyl precursor the only -

in close proximity to t to proximity close in A likely to be detoxified (inactivated) and have potential to damage cells/DN damage to potential have and (inactivated) detoxified be to likely breast cell/DNA). Neither cell/DNA). breast the (i.e. formation heir

ficient levels of minerals (selenium, iodine) and vitami and iodine) (selenium, minerals of levels ficient f insu to due , w lo is glutathione if , r Howeve estrogens are less less are estrogens quinone the E), and (C ns

. . y hungry molecules in the body are inactivated when bound to glutathione, the mo the glutathione, to bound when inactivated are body the in molecules hungry - electron and oxidized in the bod the in antioxidant ubiquitous st

These estrogen qui estrogen These and this occurs rapidly in the presence of oxidized lipids, especially those from trans from those especially lipids, oxidized of presence the in rapidly occurs this and nones, like all all like nones, fats. hydrogenated -

The 2 The hydroxy estrogens are converted to their more dangerous oxidized quinone for quinone oxidized dangerous more their to converted are estrogens hydroxy - 4 and - sulfation. ions in the cell, cell, the in ions condit oxidizing under ms

or by glutathione glutathione by or methylation by nactivated i not are they if risk cancer breast increased with associated are estrone and estradiol of quinones

forming adducts that lead to permanent mutations in the DNA. Many studies have shown that high urina high that shown have studies Many DNA. the in mutations permanent to lead that adducts forming ones of of ones quin - 4 these of levels ry

A highly reactive estrogen quinones. Estrogen quinones, especially the 4 the especially quinones, Estrogen quinones. estrogen reactive highly lic and bind to DN to bind and lic electrophi highly are one estr and estradiol of quinone -

h is oxidation to to oxidation is h whic metabolism, of thway pa dangerous and insidious more a take can estrogens hydroxyl - 4 and - 2 the betaine) folate, B12, B6,

or lack lack or T ion (i.e. vitamins vitamins (i.e. ion methylat of precursors of COM of levels low to due inadequate are pathways methylation If urine. in excreted rapidly

he methylated catechol es catechol methylated he t form this In 2010). 79, - 75 6(1): Oncol Future EG Rogan EL, (Cavalieri harmless and inert estrogens trogens are are trogens

ransferase (COMT), (COMT), ransferase T which renders these catec these renders which Methyl - o - Catechol enzyme the by methylated are estrogens hydroxyl - 4 and - 2 The hol hol

. . r risk for breast cance breast for risk

ngerous estrogen quinones estrogen ngerous da more to converted likely less and inert, rendered are metabolites estrogen hydroxylated dangerous that increase increase that

the potentially potentially the indicates this as ficial bene is E2 - and E1 - MeO - 4 the particularly estrogens, - methoxy of levels elevated to range - Mid E1. - MeO

scade). Estrone is then m then is Estrone scade). Ca Metabolism Steroid (see estrone to estradiol converts which II, type dehydrogenase hydroxysteroid - 4 to ethylated

. Progesteron . y e induces synthesis/activ induces e therap progesterone natural with combination in therapy replacement estrogen of result ation of 17 beta beta 17 of ation

Th E1, which is high. is which E1, - MeO - 4 of exception the with range mid within are hydroxyestrogens - 4 - and - 2 the of forms methylated The is is likely a a likely is is

TION OF HYDROXYESTROGENS OF TION A METHYL

predicting breast cancer risk. cancer breast predicting

1: 60 1: 1 7 Acta Chimica Analytica t shown the 2/16 ratio to ratio 2/16 the shown t no have studies recent more Overall, 2012). 68, - et.al. J (Huang women be useful for for useful be

, associated wi associated , y stmenopausal stmenopausal po in risk decreased a th paradoxicall are, levels higher women, premenopausal in risk cancer breast increased

2018 07 01 007 U 007 01 07 2018 Comments | REPORT TEST # continued

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11 of 9

cortisol is not first corrected by lifestyle interventions or medications. or interventions lifestyle by corrected first not is cortisol

These th These . y be successful if low low if successful be to likely not are erapies deficienc cortisol of symptoms exacerbate and levels cortisol lower further may therapies

Thyro and nutritional supplements (vitamins C and B5) are some of the natural ways to help support adrenal support help to ways natural the of some are B5) and C (vitamins supplements nutritional and id or androgen androgen or id Caution: function.

Adequate sleep and rest, gentle exercise, proper diet (adequate protein), protein), (adequate diet proper exercise, gentle rest, and sleep Adequate optimal thyroid function. thyroid optimal enal extracts, herbs, herbs, extracts, enal adr progesterone, natural

and sugar craving. Low cortisol is often associated with symptoms of thyroid deficiency as normal ph normal as deficiency thyroid of symptoms with associated often is cortisol Low craving. sugar and tisol are essential for for essential are tisol cor of levels ysiological

, y cold body temp, temp, body cold sensitivit chemical n), dysfunctio (immune allergies fatigue, include cortisol low chronic with associated commonly Symptoms

cortisol levels fall below normal, as in these test results. results. test these in as normal, below fall levels cortisol

stressor persists the adrenal glands either continue to meet the demands of the stressor with high c high with stressor the of demands the meet to continue either glands adrenal the persists stressor exhausted, wherein wherein exhausted, become or output, ortisol

, if the the if , r (bacterial, viral, fungal). In a healthy individual the adrenal glands initially respond to stressor to respond initially glands adrenal the individual healthy a In fungal). viral, (bacterial, output. Howeve output. cortisol increasing by s

, diseases, inflammatory conditions), chemical exposure, low cortisol precursors (pregnenolone precursors cortisol low exposure, chemical conditions), inflammatory diseases, , y genic infections infections genic patho and progesterone) , injur

, , y psychological stress, sleep deprivation, low protein diet, nutrient deficiencies (particularly low v low (particularly deficiencies nutrient diet, protein low deprivation, sleep stress, psychological al insults (surger insults al physic B5), and C itamins

Low cortisol suggests adrenal exhaustion/low adrenal reserve, which is usually caused by some form o form some by caused usually is which reserve, adrenal exhaustion/low adrenal suggests cortisol Low nal/ emotio as such stressor f

day and are very similar to 24 hour urine values. values. urine hour 24 to similar very are and day

The total levels of these glucocorticoids are determined from the ave the from determined are glucocorticoids these of levels total The the expected reference ranges. reference expected the tions throughout the the throughout tions collec urine four of rage

otal cortisol (F) and cortisone (E), and their down their and (E), cortisone and (F) cortisol otal stream metabolites, tetrahydrocortisol (THF) an (THF) tetrahydrocortisol metabolites, stream - T E), are lower than than lower are E), (TH tetrahydrocortisone d

TICOIDS R GLUCOCO L A T O T

, which represents which , increases, which reflects an increase in the exogenous testosterone, but not Epi not but testosterone, exogenous the in increase an reflects which increases, endogenous production. endogenous T -

T/Epi ratio ratio T - the topical, cept ex system delivery any with supplemented is testosterone When circumstances. normal under 1 about be

should should of ratio The T) and testosterone (T) are created in about equal amounts from androstenedion from amounts equal about in created are (T) testosterone and T) - (Epi testosterone - Epi T - T/Epi DHEA. and e

OSTERONE. T TES O T P TIONSHI A REL AND OSTERONE T TES - EPI

likely contributes to the self the to contributes likely T or testostero or A supplementin Consider . y reported symptoms of androgen deficienc androgen of symptoms reported - Low ne. ne. DHE with g

. . r manufactured in the adrenals. Following menopause the ovarian contribution of androgens is lowe is androgens of contribution ovarian the menopause Following adrenals. the in manufactured

A of the testosterone is derived from androstenedione produced by the ovaries, and the other half from half other the and ovaries, the by produced androstenedione from derived is testosterone the of DHE of conversion peripheral

estosterone itself is derived mostly from androstenedione and D and androstenedione from mostly derived is itself estosterone T from testosterone via 5a reductase. 5a via testosterone from en about half half about en wom premenopausal In HEA.

The most potent of the androgens is dih is androgens the of potent most The are also precursors to the estrogens, estradiol and estrone. and estradiol estrogens, the to precursors also are hich is created created is hich w (DHT), ydrotestosterone

Androgens Androgens role in the brain to increase the level of neurotransmitters such as dopamine, which are important f important are which dopamine, as such neurotransmitters of level the increase to brain the in role drive. sex and elevation mood or

They also pl also They Androgens are important for strengthening structural tissues such as muscles, bone, connective tissu connective bone, muscles, as such tissues structural strengthening for important are Androgens ay an important important an ay skin. and e,

memory lapses, loss of sex drive, hot flashes, allergies). allergies). flashes, hot drive, sex of loss lapses, memory

incontinence, cardiovascular disease, insulin resistance/metabolic syndrome, breast cancer) and symp and cancer) breast syndrome, resistance/metabolic insulin disease, cardiovascular incontinence, a, depression, depression, a, stamin low (fatigue, toms

, is associated with many di many with associated is , T ferent adverse conditions (bone loss (bone conditions adverse ferent f Low androgens, particularly low DH low particularly androgens, Low dryness, dryness, vaginal skin, thinning ,

. . y reported symptoms of androgen deficienc androgen of symptoms reported - self with consistent

is the most potent of the androgens and responsible for binding and activation of intracell of activation and binding for responsible and androgens the of potent most the is T DH . w is is T lo Low DH Low receptors. androgen ular

estosterone (T) is within reference range for a postmenopausal woman, but its more potent metabolit potent more its but woman, postmenopausal a for range reference within is (T) estosterone T erone (DHT) is is (DHT) erone dihydrotestost alpha 5 e,

ABOLITES T ME AND ANDROGENS

, are within mid rang mid within are , T stream and more potent metabolite DH metabolite potent more and stream - down its or testosterone, if particularly pausal woman. pausal postmeno a for lower or e

to raise testo raise to A sterone levels, levels, sterone DHE ental supplem consider persist, symptoms androgen low If women. in levels testosterone raise to supplement

is commonly used as used commonly is A Low levels of these androgen precursors are associated with self with associated are precursors androgen these of levels Low a a DHE androgens. low of symptoms reported -

occurs in individuals with higher amounts of adipose (fat) tissue. tissue. (fat) adipose of amounts higher with individuals in occurs

rogen, estrone, estrone, rogen, est the to conversion ore M estrone. into or individuals, most in amounts equal near in testosterone - Epi and testosterone into

Androstenedione, the down the Androstenedione, rther converted converted rther fu is DHEA, of metabolite stream - blood. in life - half its extend to (DHEAS) sulfate - DHEA to sulfated

is synthesized is A in the adrenal glands an glands adrenal the in DHE glands. adrenal the by produced DHEA(S) from derives androstenedione the of most d is rapidly rapidly is d

At alf from the adrenals. the from alf h other the and ovaries the from derived is androstenedione the of half about women premenopausal In menopause, menopause,

menopausal woman. woman. menopausal post a for ranges reference normal than lower are DHEA, and androstenedione precursors, androgen The

ANDROGEN PRECURSORS (ANDROSTENEDIOL, DHEA) (ANDROSTENEDIOL, PRECURSORS ANDROGEN

a mineralocorticoid (see DOC results). DOC (see mineralocorticoid a - (DOC) deoxycorticosterone and/or allopregnanolone

This is likely due to excessiv to due likely is This one to to one progester of conversion e headaches. and breasts, sore and swollen retention, water sleepiness,

, some women poorly tolerate oral progesterone as the metabolites the as progesterone oral tolerate poorly women some , r that form from it may ca may it from form that Howeve cancers. breast and uterine use excessive excessive use

risks for cardiovascular for risks regards as safe be to studies numerous by shown been has dosing oral mg 300 - 100 at progesterone Oral disease, disease,

fe f sleep and calming progesterone's oral to contributes This (anxiolytic). fect f cts. cts. e inducing - e calming

rece A ptors and induces a a induces and ptors GAB to binds it ere wh blood, the from brain the enters freely and bioactive is allopregnanolone, these, of One results.

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dvanced Metabolites dvanced A

diagnosis and treatment. and diagnosis

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11 of 10

production by exposure to light during the night. the during light to exposure by production

, b , " humans to carcinogenic probably is disruption circadian involves that work shift " concluded that that concluded of melatonin melatonin of suppression the of ecause

Agency for Research Research for Agency Internati WHO's The Low night time melatonin levels are seen in breast and prostate cancer patients. cancer prostate and breast in seen are levels melatonin time night Low on Cancer has has Cancer on onal

work. work.

225, 2012). Low melatonin is also thought to contribute to a susceptibility to obesity in p in obesity to susceptibility a to contribute to thought also is melatonin Low 2012). 225, - 194 (2): ose who do night shift shift night do who ose th or insomnia with eople

Agin dementia), pain disorders, cardiovascular disease, cancers of the breast and prostate, and type 2 di 2 type and prostate, and breast the of cancers disease, cardiovascular disorders, pain dementia), g and Disease 3 3 Disease and g R. (Hardeland abetes

ferent dysfunctions and diseases such as immune dysfunction, neurodegenerative disorder neurodegenerative dysfunction, immune as such diseases and dysfunctions ferent f with many di many with enile enile s disease, (Alzheimer's s

n associated associated n bee has calcification eal pin by caused melatonin Low estrogens). decreases and progesterone increases (melatonin progesterone

formation and growth of tumors such as breast and prostate cancers, and helps regulate the synthesis the regulate helps and cancers, prostate and breast as such tumors of growth and formation adiol and and adiol estr hormones - sex the of

. It helps slow the aging pr aging the slow helps It . y bod the in fects f e beneficial ferent f Melatonin is known to have many di many have to known is Melatonin xidant, inhibits inhibits xidant, o - anti potent a is ocess,

melatonin. melatonin.

out its restorative properties. Melatonin synthesis decreases with aging and calcification of the pi the of calcification and aging with decreases synthesis Melatonin properties. restorative its out very low production of of production low very in result can gland neal

Melatonin produced by the pineal gland in the brain and released into the circulation rapidly enters rapidly circulation the into released and brain the in gland pineal the by produced Melatonin ody where it carries carries it where ody b the throughout tissues

of urine and measurement of MT6s. of measurement and urine of

These circadian patterns of melaton of patterns circadian These 2 about , y hormones reach their nadir and peak, respectivel peak, and nadir their reach hormones h time collections collections time h wit tracked easily are in am. 3 -

and then gradually begins to rise again with nightfall and less light exposure. Cortisol continues t continues Cortisol exposure. light less and nightfall with again rise to begins gradually then and again, when both both when again, rises melatonin as fall o

nin reaches a nadir nadir a reaches nin melato afternoon - mid By . light to exposure and waking after hr 1 to min 30 about peaking rise, to begins cortisol and rapidly

. With morning an morning With . y 3 am, while cortisol falls to a nadir at this time of da of time this at nadir a to falls cortisol while am, 3 - 2 about peak and darkness , melatonin drops drops melatonin , exposure light of onset d

In a healthy individual, the circadian rhythm of melatonin is inversely related to cortisol, i.e. me i.e. cortisol, to related inversely is melatonin of rhythm circadian the individual, healthy a In th th wi rise saliva and urine, blood, in levels latonin

. . r afternoon nadi afternoon

The last collection, just before b before just collection, last The amount of light exposure, should represent the lowest MT6s level. MT6s lowest the represent should exposure, light of amount rising from the the from rising MT6s the show should ed,

The third urine void in the late aft late the in void urine third The should show MT6s dropping rapidly from the early morning value. morning early the from rapidly dropping MT6s show should the greatest greatest the represents which ernoon,

, , r early morning first void MT6s ideal for measuring melatonin levels when it is peaking about 2 about peaking is it when levels melatonin measuring for ideal MT6s void first morning early bout 2 hr late hr 2 bout a void, urine second The am). 3 -

, which makes makes which , gland and presence in the bloodstream is highest (note: MT6s levels in urine lag behind blood and sa and blood behind lag urine in levels MT6s (note: highest is bloodstream the in presence and gland r h 3 - 2 about levels livary

. MT6s in the first morning urine is representative of the average night time melatoni time night average the of representative is urine morning first the in MT6s . y during the da the during nthesis by the pineal pineal the by nthesis sy its when production, n

ferent time points points time ferent f MT6s, a metabolite of melatonin found in urine, is used as a surrogate marker to follow the circadia the follow to marker surrogate a as used is urine, in found melatonin of metabolite a MT6s, di at melatonin of rhythm n

.nlm.nih.gov/medlineplus/druginfo/natural/940.html). w http://ww

high levels of estrogens, progesterone, androgens, cortisol, thyroid hormones). Consider melatonin s melatonin Consider hormones). thyroid cortisol, androgens, progesterone, estrogens, of levels high raindications (see: (see: raindications cont no if upplementation

reported issues with sleep disturbances, which may be related to low melatonin production as well as well as production melatonin low to related be may which disturbances, sleep with issues reported s (e.g. low or or low (e.g. s imbalance hormonal other

This This The urine melatonin metabolite MT6s is low throughout the day and not showing a normal circadian rhy circadian normal a showing not and day the throughout low is MT6s metabolite melatonin urine The - self has individual pattern). (flat thm

ONIN (MT6s) ONIN T A OXYMEL T A F 6 ABOLITE T ME ONIN T A SUL - MEL

Axis in Chronic Disease Management Disease Chronic in Axis A P H the and Stress of Role The " McEwen; Bruce by " Thomas G Thomas by " It uilliams, PhD. uilliams,

The Cortisol Connection Cortisol The " Ph.D.; D.C., N.D., Wilson, L. James by , " Fatigue Adrenal e Know Know e W As Str of End The " albot T Shawn by , " " ess Ph.D.; t,

For additional information about strategies for supporting adrenal health and reducing stress(ors), stress(ors), reducing and health adrenal supporting for strategies about information additional For orth reading: reading: orth w are books following the

fects associated with chronic low cortisol. low chronic with associated fects f adrenal exhaustion or the adverse e adverse the or exhaustion adrenal

Adrenal support and reducing stressor(s) as much as as much as stressor(s) reducing and support Adrenal . r production to meet the demands of the stresso the of demands the meet to production ered to avoid avoid to ered consid be should possible

, cold body temp, and sugar craving. If stressors persist, this can result in adrenal fat adrenal in result can this persist, stressors If craving. sugar and temp, body cold , y sensitivit continue cortisol cortisol continue to inability the and igue

unction), chemical chemical unction), dysf (immune allergies e, fatigu as such symptoms to leads often B5) and C vitamins (particularly deficiencies nutrient and/or

, r sleep deprivation, deprivation, sleep stresso chronic a by is synthes cortisol adrenal of Depletion function. immune optimize and production), energy and function

, help regulate st regulate help , y (important for brain brain for (important levels glucose state eady activit metabolic normal maintain to essential is cortisol of output daily normal

A and fungi). and viruses (bacteria, tions infec pathogenic and progesterone) and (pregnenolone precursors cortisol of levels low medications),

, diabetes), chemical exposu chemical diabetes), , r (cance diseases injury), , y nts, excessive excessive nts, polluta (environmental re (surger insults physical B5), and C vitamins

(particularly low low (particularly deficiencies nutrient s), vegetarian in problematic particularly - protein (low diet poor deprivation, sleep (emotional), stress

de: psychological psychological de: inclu which stressors by caused commonly most is fatigue) adrenal or exhaustion adrenal as to referred (often Hypocortisolism

adrenal glands. glands. adrenal the by synthesis cortisol endogenous suppresses which indicated), (none use glucocorticoid synthetic

. Hypocortisolism is usually precipitated by some type of chronic stressor followed by adrenal ex adrenal by followed stressor chronic of type some by precipitated usually is Hypocortisolism . y the result of of result the be also can but haustion, da

ges throughout the the throughout ges ran reference than lower are but rhythm circadian normal a following somewhat are (E) cortisone and (F) cortisol free Urinary

TISONE (E) TISONE R CO AND (F) L TISO R CO FREE Y R URINA

by Kenna Stephenson, MD. Stephenson, Kenna by " Athena wakening A " McEwen; Bruce by " It Know e W As Stress

albott, Ph. albott, T Shawn by , " Connectio Cortisol The " Ph.D.; D.C., N.D., Wilson, L. James by , " Fatigue Adrenal " The End of of End The " D.; D.; n reading: worth are

l, the following books books following the l, cortiso deplete that sors stres reducing and function gland adrenal supporting for strategies about information additional For

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11 of 11

. y during the da the during sleepiness persistent with associated is this and hours daylight the throughout excessive are levels

. Consider dosage re dosage Consider . w duction if MT6s MT6s if duction lo e b should levels when evening the into over - carry often and voids, urine second and first the in MT6s

This will be seen as as seen be will This melatonin normal the of disruption and , y very high levels of of levels high very ms. rhyth circadian cortisol - da the during sleepiness excessive

ylight hours, hours, ylight da into melatonin of over spill in result can dosing Excessive timing. and dosage melatonin with familiar provider care health

fectiveness, especially as a sleep aid. Response to supplemental melatonin can be very individual. very be can melatonin supplemental to Response aid. sleep a as especially fectiveness, f s best to work with a a with work to best s i it benefit optimal For e

mportant to its its to mportant i are dosage and timing e th condition, a treat or levels low correct to OTC) (available supplement a as taken is melatonin If

controversial. controversial.

, its utility for the treatment of treatment the for utility its , r hed and remains remains and hed establis not is insomnia howeve individuals; blind totally in found commonly most disorder

, and the non the and , r d worker shift lag, jet , r our sleep our h - 24 - isorde disorde phase sleep delayed as such disorders, sleep rhythm circadian with wake wake -

useful in people people in useful found been has melatonin exogenous with treatment rhythm, circadian the of regulation the in role established its of Because

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dvanced Metabolites dvanced A