DUTCH Complete Male Sample Report 6 - 21 - 18

Accession # 00280402
Male Sample Report

123 A Street
Sometown , CA 90266
Ordering Physician: DOB: 1966-05-06 Collection Times:

Precision Analytical Age: 50 2016-10-01 06:01AM
2016-10-01 08:01AM
Gender: Male 2016-10-01 06:01PM
2016-10-01 10:01PM
Hormone Testing Summary
Key (how to read the results): Sex Hormones

Testosterone
Age Range
25
patient
19 47 18-25 50-115
low limit high limit
result 10 34 115 26-40 40-95
41-60 30-80
Total Estrogen Testosterone
(Sum of 8 Estrogen Metabolites) >60 25-60
See Pages 2 & 3 for a thorough breakdown of sex hormone metabolites
Adrenal Hormones See pages 4 and 5 for a more complete breakdown of adrenal hormones
Total DHEA Production

200 H
ig 1000 5500
h
Age Range 3439
(ng/mg)
R
Daily Free
a
n Cortisol Pattern 20-39 3000-5500
g
160 e 40-60 2000-4000
Li
m >60 1000-2500
it Total DHEA Production
(DHEAS + Etiocholanolone + Androsterone)
Cortisol
120
80 Patient Values
100 4550
171 5215
40 Lo w 310 10000
Ra ng
e Limit
24hr Free Cortisol cortisol Metabolized Cortisol (THF+THE)
0 (A+B+C+D) metabolism (Total Cortisol Production)
Waking (A) Morning (B) Afternoon (C) Night (D)
Free cortisol best reflects tissue levels. Metabolized cortisol best reflects total cortisol production.
Please be sure to always read below for any specific lab comments. More detailed comments can be found on page 8.
=======================================================================================
Your DUTCH Complete report will inc lude a summary (page 1), a list of all of the hormones tested and their ranges (pages 2,4,6) as well as a
graphic al representation of the results (pages 3,5). You will also see a steroid pathway for your referenc e (page 7) and provider notes.
This report is not intended to treat, c ure or diagnose any spec ific diseases.
There is a series of videos in our video library at dutc htest.c om that you may find useful in understanding the report. The following videos (whic h
c an also be found on the website under the listed names) may be partic ularly helpful in aiding your understanding:
DUTCH Complete Overview
Estrogen Tutorial; Androgen and cortisol videos pending.
Precision Analytical (Raymond Grimsbo, Lab Director) Male Sample Report Page 1 of 13
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Male Sample Report
123 A Street
Sometown , CA 90266
Sex Hormones and Metabolites

2016-10-01 08:01AM
Gender: Male 2016-10-01 06:01PM
2016-10-01 10:01PM
Category Test Result Units Normal Range

Progesterone Metabolites (Urine)
b-Pregnanediol Low end of range 107.0 ng/mg 75 - 400
a-Pregnanediol Low end of range 40.0 ng/mg 20 - 130
Estrogens and Metabolites (Urine)
Estrone(E1) Within range 8.5 ng/mg 4 - 16
Estradiol(E2) Within range 0.94 ng/mg 0.5 - 2.2
Estriol(E3) Low end of range 2.0 ng/mg 2-8
2-OH-E1 High end of range 4.74 ng/mg 0 - 5.9
4-OH-E1 Within range 0.38 ng/mg 0 - 0.8
2-Methoxy-E1 Within range 1.05 ng/mg 0 - 2.8
2-Methoxy-E2 Within range 0.5 ng/mg 0 - 0.8
Androgens and Metabolites (Urine)
DHEA-S Within range 1195.0 ng/mg 30 - 1500
Androsterone Within range 1461.0 ng/mg 500 - 3000
Etiocholanolone Within range 783.0 ng/mg 400 - 1500
Testosterone Within range 46.8 ng/mg 25 - 115
5a-DHT Low end of range 7.9 ng/mg 5 - 25
5a-Androstanediol Low end of range 35.4 ng/mg 30 - 250
5b-Androstanediol Low end of range 57.7 ng/mg 40 - 250
Epi-Testosterone Low end of range 35.6 ng/mg 25 - 115
Hormone metabolite results from the previous page are presented here as they are found in the
steroid cascade. See the Provider Comments for more information on how to read the results.
Age-Dependent Ranges
Androgens
Age DHEA-S
20-39 150-1500
Pregnenolone
40-60 60-800
30 >60 30-300
1195
Etiocholanolone Androsterone
1500 20-39 800-1500 20-39 1500-3000
DHEA 40-60 600-1200 40-60 1000-2000
DHEA-S >60 400-1000 >60 500-1000
5ß-androstanediol 5α-androstanediol
20-39 70-250 20-39 60-250
40-60 55-210 40-60 50-180
Androstenedione 25
47 >60 40-150 >60 30-130
5α
5ß
ar 115 Testosterone 5α-DHT

om
at 18-25 50-115 20-39 9-25
as 26-40 40-95 40-60 7-20
e Testosterone
41-60 30-80 >60 5-16
ar
om >60 25-60
at
as
400 1500 500 3000 e
783 1461
Etiocholanolone Androsterone
Testosterone
5α 8.5 0.94 2.0
5ß
4.0 16.0 0.50 2.20 2.0 8.0

CYP3A4
Estrone(E1) Estradiol(E2) Estriol(E3)
Less Androgenic
Metabolites primary estrogens (E1, E2, E3)
5.0
7.9
CY
25.0
P3
A4
5a-DHT
Estrogens
0.65
1.20
0.00
40
58 30
35 16-OH-E1 Phase 1 Estrogen Metabolism Ratios
CYP
CYP1A1 (protective pathway)
1 B1
250 250
5b-Androstanediol 5a-Androstanediol
Patient 2-OH 4-OH 16-OH

5ß preference 5α Preference Percentages 82.2% 6.6% 11.3%
(androgenic)
Expected 60-80% 7.5-11% 13-30%
0.38 Percentages (2-OH) (4-OH) (16-OH)
5α-Reductase Activity
0.80
5α -metabolism makes androgens more potent, most 0.00
notably 5α -DHT is the most potent testosterone metabolite 4-OH-E1
Glutathione detox
Low High QUINONE

COMT
1.05 4.74 (reactive)
2.80 methylation 5.90

0.00 0.00
Methylation-activity 2-Methoxy-E1 2-OH-E1
2-Methoxy/2-OH
Methylation detox
4-OH-E1
If not detoxified, 4-OH-E1 can

bind to and damage DNA
Male Sample Report
123 A Street
Sometown , CA 90266
Adrenal
2016-10-01 08:01AM
Gender: Male 2016-10-01 06:01PM
2016-10-01 10:01PM

Creatinine (Urine)
Creatinine A (Waking) Within range 1.1 mg/ml 0.3 - 3
Creatinine B (Morning) Within range 0.93 mg/ml 0.3 - 3
Creatinine C (Afternoon) Within range 0.9 mg/ml 0.3 - 3
Creatinine D (Night) Within range 1.13 mg/ml 0.3 - 3
Daily Free Cortisol and Cortisone (Urine)
Cortisol A (Waking) Within range 54.9 ng/mg 18 - 80
Cortisol B (Morning) Low end of range 68.7 ng/mg 50 - 200
Cortisol C (Afternoon) Within range 26.6 ng/mg 13 - 55
Cortisol D (Night) High end of range 21.1 ng/mg 0 - 25
Cortisone A (Waking) Above range 162.6 ng/mg 50 - 140
Cortisone B (Morning) Within range 177.8 ng/mg 100 - 240
Cortisone C (Afternoon) Above range 149.3 ng/mg 40 - 115
Cortisone D (Night) Above range 94.4 ng/mg 0 - 70
24hr Free Cortisol Within range 171.3 ng/mg 100 - 310
24hr Free Cortisone Above range 584.0 ng/mg 250 - 500
Cortisol Metabolites and DHEA-S (Urine)
a-Tetrahydrocortisol (a-THF) Within range 419.0 ng/mg 175 - 700
b-Tetrahydrocortisol (b-THF) Low end of range 1961.0 ng/mg 1750 - 4000
b-Tetrahydrocortisone (b-THE) Low end of range 2835.0 ng/mg 2350 - 5800
Metabolized Cortisol (THF+THE) Low end of range 5215.0 ng/mg 4550 - 10000
DHEA-S Within range 1195.0 ng/mg 30 - 1500
ST R ESS
Stress (or inflammation)

Hypothalamus Total DHEA Production
CRH
causes the brain to release ACTH,

which stimulates the adrenal glands Age Range
Pituitary 20-39 3000-5500
to make hormones
40-60 2000-4000
Pineal >60 1000-2500
10
61
ACTH
85
Melatonin* (Waking) 1000

3439 5500
Total DHEA Production

Adrenal Gland DH EA (DHEAS + Etiocholanolone + Androsterone)
4550
5215
10000
Metabolized Cortisol (THF+THE)

Cor Cortisol Metabolism (Total Cortisol Production)
tis ol
Cir
cu
lat
ing
More cortisone More cortisol

Fre
metabolites (THE) metabolites (THF)

eC
NOTE: This 11b-HSD index measures the balance of cortisol and cortisone metabolites
ort
which best reflects the overall balance of active cortisol and inactive cortisone systemically.
iso
400 200 H
ig
h
(ng/mg)
Cortisone (ng/mg)
an R
Daily Free Cortisone Pattern Daily Free Cortisol
ge Pattern
320 160 Li
m
it
Cortisol
Hig
240 hR 120
a ng
eL
Patient Values imi
t
160 80 Patient Values
80 Lo w R 40 Lo w
a nge Ra n g
Limit e Limit
0 0
Waking (A) Morning (B) Afternoon (C) Night (D) Waking (A) Morning (B) Afternoon (C) Night (D)
e interconv ert
C ortis on (11b-
l and HS D
tis o )
Co r
250 100
584 171
500 310
24hr Free Cortisone 24hr Free Cortisol

(A+B+C+D) (A+B+C+D)
The first value reported (Waking "A") for c ortisol is intended to represent the "overnight" period. When patients sleep through the night, they
c ollec t just one sample. In this c ase, the patient woke during the night and c ollec ted (see the top of the report for the times c ollec ted). We c all
this value "A1" and the value from the sample c ollec ted at waking "A2." These values are used to c reate a "time-weighted average" to c reate the
"A" value. The individual values are listed here for your use:
The middle-of-the-night "A1" sample registered a cortisol value of 9.9ng/mg.
The waking "A2" sample registered a cortisol value of 87.1ng/mg.
These two values are averaged together, taking into account the amount of time each one represents, to create the "A" value of approximately
54.9ng/mg that you will see on the report.
In this particular case, this A2 value is larger than the sample (collected two hours after waking) expected to have the highest cortisol value.
Cortisol levels typically rise sharply after waking thanks to the cortisol awakening response. In a case like this where the waking sample (A2)
shows higher levels, this cortisol awakening response may have happened while the patient was in bed before rising.
Male Sample Report
123 A Street
Sometown , CA 90266
Organic Acid Tests (OATs)

2016-10-01 08:01AM
Gender: Male 2016-10-01 06:01PM
2016-10-01 10:01PM

Nutritional Organic Acids
Vitamin B12 Marker (may be deficient if high) - (Urine)
Methylmalonate (MMA) Within range 1.4 ug/mg 0-3
Vitamin B6 Marker (may be deficient if high) - (Urine)
Xanthurenate Within range 0.8 ug/mg 0 - 2.1
Glutathione Marker (may be deficient if low or high) - (Urine)
Pyroglutamate Low end of range 44.1 ug/mg 43 - 85
Neurotransmitter Metabolites
Dopamine Metabolite - (Urine)
Homovanillate (HVA) Low end of range 5.3 ug/mg 4.8 - 19
Norepinephrine/Epinephrine Metabolite - (Urine)
Vanilmandelate (VMA) Low end of range 3.1 ug/mg 2.8 - 8
Serotonin Metabolite - (Urine)
5-Hydroxyindoleacetate (5HIAA) Below range 2.8 ug/mg 3 - 10
Melatonin (*measured as 6-OH-Melatonin-Sulfate) - (Urine)

Melatonin* (Waking) Within range 61.2 ng/mg 10 - 85
Oxidative Stress / DNA Damage, measured as 8-Hydroxy-2-deoxyguanosine (8-OHdG) - (Urine)
8-OHdG (Waking) Within range 2.8 ng/mg 0 - 8.8
Provider Notes
How to read the DUTCH report
The graphic dutch dials in this report are intended for quick and eas y evaluation of which hormones are out of range. Res ults
below the left s tar are s haded yellow and are below range (left). Res ults between the s tars and s haded green are within the
reference range (middle). Res ults beyond the s econd s tar and s haded red are above the reference range (right). Some of
thes e hormones als o change with age, and the age-dependent ranges provided s hould als o be cons idered.
In a few places on the graphical pages , you will s ee fan-s tyle gauges . For s ex hormones , you will s ee one for the balance
between 5a/5b metabolis m as well as methylation. For adrenal hormones , you will s ee one to repres ent the
balance between cortis ol and cortis one metabolites . Thes e indexes s imply look at the ratio of hormones for a
preference. An average or "normal" ratio between the two metabolites (or groups of metabolites ) will give a
res ult in the middle (as s hown here). If the ratio between the metabolites meas ured is "low" the gauge will lean
to the left and s imilarly to the right if the ratio is higher than normal.
Patient or Sample Comments

Throughout the provider comments you may find s ome comments s pecific to your s ituation or res ults . Thes e comments will
be found in this s ection or within another s ection as appropriate. Comments in other s ections that are s pecific to your cas e
will be in bold.
Note: The dates lis ted on the s amples imply that they were older than our allowed 3 weeks when they were received. The
ins tructions as k that patients freeze or refrigerate s amples if they are to be held. If that is not the cas e, the free cortis ol and
cortis one levels may drop s omewhat over time if the s amples are too old. Other hormones tes ted are s table for more than
12 weeks at room temperature. Samples that are refrigerated or frozen are s table for months .
Androgen Metabolism
When evaluating androgen levels , it is important to as s es s the following:
The status (low, normal or high?) of DHEA:
DHEA and andros tenedione are made almos t exclus ively by the adrenal gland (although a s maller amount is made in the
ovaries ). Thes e hormones appear in urine as DHEA-S (DHEA-Sulfate), andros terone and etiocholanolone. The bes t way to
as s es s the total production of DHEA is to add up thes e three metabolites . This total can be s een on the firs t page of the
DUTCH Complete (and DUTCH Plus ). DHEA production decreas es quite s ignificantly with age. Age-dependent ranges can be
s een on the graphical page of res ults .
The Total DHEA Production (page 1) was about 3,439ng/mg which is within the overall range and also within
the age-dependent range for this patient. This implies that the adrenal glands are producing appropriate DHEA
levels.
The status (low, normal or high?) of testosterone:

The tes tes make mos t of the male's tes tos terone. Levels tend to be their highes t at around 20 years of age and s tart to
decline when men get into their 30's . Levels continue to drop as men age. Cons ider the appropriate age-dependent range for
your patient. In older men, you can als o cons ider the 18-25 year-old group to approximate what levels may have been when
the patient was young and relatively healthy.
The metabolic preference for the 5a (5-alpha) or 5b (5-beta) pathway:

5a-reductas e converts tes tos terone into 5a-DHT (DHT), which is even more potent (~3x) than tes tos terone. High levels of
DHT can lead to s ymptoms as s ociated with too much tes tos terone (thinning s calp hair, acne, etc.) and may als o be
as s ociated with pros tate is s ues in older men. Metabolites created down the 5b-pathway are s ignificantly les s androgenic
than their 5a counterparts . In the examples below, the example on the left s hows a patient with 5b-metabolis m preference. A
patient with a pattern like the example on the right may have high androgen s ymptoms even though tes tos terone is in the
normal range becaus e of the likely preference for turning a lot of his tes tos terone into DHT. The fan-s tyle gauge below the
hormones s hows the 5a or 5b preference bas ed on the balance between etiocholanolone (5b) and andros terone (5a) as well
as 5a-andros tanediol and 5b-andros tanediol.
You will als o s ee levels of epi-tes tos terone, which is not androgenic like tes tos terone. It happens to be produced in about the
s ame concentrations as tes tos terone (this is an approximate relations hip). This can be helpful to as s es s tes tos terone
therapy and rare cas es where tes tos terone may have other complexities .
Estrogen Metabolism
When evaluating estrogen levels, it is important to assess the following:
The status (low, normal or high?) of estrogen production:
Levels of the primary es trogen, es tradiol (the s tronges t es trogen), as well as "total es trogens " may be cons idered.
Phase I Metabolism:
Es trogen is metabolized (primarily by the liver) down three phas e I pathways . The 2-OH pathway is cons idered the s afes t
becaus e of the anti-cancer properties of 2-OH metabolites . Convers ely, the 4-OH pathway is cons idered the mos t genotoxic
as its metabolites can create reactive products that damage DNA. The third pathway, 16-OH creates the mos t es trogenic of
the metabolites (although s till cons iderably les s es trogenic than es tradiol) - 16-OH-E1.
When evaluating phas e I metabolis m, it may be important to look at the ratios of the three metabolites to s ee which
pathways are preferred relative to one another. It may als o be important to compare thes e metabolites to the levels of the
parent hormones (E1, E2). If the ratios of the three metabolites are favorable but overall levels of metabolites are much
lower than E1 and E2, this may imply s luggis h phas e I clearance of es trogens , which can contribute to high levels of E1 and
E2.
The pie chart will as s is t you in comparing the three pathway options of phas e I metabolis m compared to what is "normal." 2-
OH metabolis m can be increas ed by us ing products containing D.I.M. or I-3-C. Thes e compounds are found (or created from)
in cruciferous vegetables and are known for promoting this pathway.
Methylation (part of Phase II Metabolism) of estrogens:
After phas e I metabolis m, both 4-OH and 2-OH (not 16-OH) es trogens can be deactivated and eliminated by methylation. The
methylation-activity index s hows the patient's ratio of 2-Methoxy-E1 / 2-OH-E1 compared to what is expected. Low methylation
can be caus ed by low levels of nutrients needed for methylation and/or genetic abnormalities (COMT, MTHFR). The COMT
enzyme res pons ible for methylation requires magnes ium and methyl donors . Deficiencies in folate or vitamin B6 or B12 can
caus e low levels of methyl donors . MTHFR genetic defects can make it more difficult for patients to make s ufficient methyl
donors . Genetic defects in COMT can make methylation poor even in the pres ence of adequate methyl donors .
Proges terone levels are of marginal value in men, although deficiency can be as s ociated with s ome clinical conditions s uch
as depres s ion, fatigue, and low libido.
DUTCH Adrenal
The HPA-Axis refers to the communication and interaction between the hypothalamus (H) and pituitary (P) in the brain down to
the adrenal glands (A) that s it on top of your kidneys . When a phys ical or ps ychological s tres s or occurs , the hypothalamus
tells the pituitary to make ACTH, a hormone. ACTH s timulates the adrenal glands to make the s tres s hormone, cortis ol and
to a les s er extent DHEA and DHEA-S. Normally, the HPA-axis production follows a daily pattern in which cortis ol ris es rather
rapidly in the firs t 10-30 minutes after waking in order to help with energy, then gradually decreas es throughout the day s o
that it is low at night for s leep. The cycle s tarts over the next morning. Abnormally high activity occurs in Cus hing’s Dis eas e
where the HPA-axis is hyper-s timulated caus ing cortis ol to be elevated all day. The oppos ite is known as Addis on’s Dis eas e,
where cortis ol is abnormally low becaus e it is not made appropriately in res pons e to ACTH’s s timulation. Thes e two
conditions are s omewhat rare. Examples of more common conditions related to les s s everely abnormal cortis ol levels
include fatigue, depres s ion, ins omnia, fibromyalgia, anxiety, inflammation and more.
Only a fraction of cortis ol is "free" and bioactive. This fraction of cortis ol is very important, but levels of metabolized cortis ol
bes t repres ent overall production of cortis ol therefore both s hould be taken into account to correctly as s es s adrenal
function.
When evaluating cortisol levels, it is important to assess the following:
The overall up-and-down pattern of free cortisol throughout the day, looking for low and high levels:
Abnormal res ults s hould be cons idered along with related s ymptoms . Remember that with urine res ults , the “waking”
s ample reflects the night’s total for free cortis ol. The s ample collected two hours after waking captures the cortis ol
awakening res pons e, which is typically the time with the mos t cortis ol s ecretion.
The sum of the free cortisol as an expression of the overall tissue cortisol exposure:
This total of four free cortis ol meas urements is the bes t way to as s es s the total of free cortis ol throughout the day, and this
res ult correlates reas onably well to a true 24-hour urine free cortis ol. Do be aware that this meas urement does not take into
account trans itory s hifts in cortis ol in the late morning or early afternoon.
The total level of cortisol metabolites:
We call this calculation "Metabolized Cortis ol" which is the s um of a-THF, b-THF and b-THE (the mos t abundant cortis ol
metabolites ). While free cortis ol is the bes t as s es s ment for tis s ue levels of cortis ol, it only repres ents 1-3% of the total
produced. The majority of cortis ol res ults in a urine metabolite and the total of thes e metabolites bes t repres ents the total
glandular output of cortis ol for the day. When overall production is much higher than free cortis ol levels , cortis ol clearance
may be increas ed (as s een in hyperthyroidis m, obes ity, etc.) The mos t common reas on for s luggis h cortis ol clearance
(as s umed when free cortis ol levels are much higher than metabolized cortis ol) is low thyroid.
Overall cortisol levels are appropriate as both free and metabolized cortisol levels are within range. If the
diurnal pattern of the free cortisol is as expected, this implies normal HPA-Axis cortisol production.
A potential preference for cortisol or cortisone (the inactive form):

Looking at the comparis on between the total for free cortis ol and free cortis one is NOT the bes t indication of a pers on's
preference for cortis ol or cortis one. The kidney converts cortis ol to cortis one in the local tis s ue. This localized convers ion
can be s een by comparing cortis ol (free) and cortis one levels . To s ee the patient’s preference s ys temically, it is bes t to look
at which metabolite predominates (THF or THE). This preference can be s een in the fan s tyle gauge. This is known as the
11b-HSD index. The enzyme 11b-HSD II converts cortis ol to cortis one in the kidneys , s aliva gland and colon. 11b-HSD I is
more active in the liver, fat cells and the periphery and is res pons ible for reactivating cortis one to cortis ol. Both are then
metabolized by 5a-reductas e to become tetrahydrocortis ol (THF) and tetrahydrocortis one (THE) res pectively.
Nutritional Organic Acids

The following three organic acids are functional markers for vitamin deficiency. Thes e compounds es s entially back up in
human biochemis try when a key nutrient is mis s ing. Thes e three metabolites have fairly s traightforward interpretations .
When the markers are elevated, it is likely that the patient's cellular levels of the related nutrient may be ins ufficient.
Methylmalonate (MMA)
Methylmalonate (als o known as methylmalonic acid or MMA) is a functional marker of vitamin B12 (als o known as cobalamin)
deficiency. When cellular levels of B12 are low either from deficiency or due to a B12 trans porter gene mutation, levels of
MMA increas e. This marker is cons idered s uperior to meas uring s erum B12 levels directly. A 2012 publication by Miller
s howed that 20% of thos e tes ted had a genetic defect in the protein that trans ports B12 to cells . Thes e patients may have a
functional B12 deficiency even if s erum levels of B12 are normal.
If levels of MMA are elevated, it may be advis able to increas e B12 cons umption. Common foods high in B12 include beef
liver, s ardines , lamb, wild caught s almon, gras s -fed beef, nutritional yeas t and eggs . Vitamin B12 levels can als o be
increas ed through s upplementation of B12 (taken as cobalamin, methylcobalamin, hydroxycobalamin, or adenos ylcobalamin).
Symptoms of a vitamin B12 deficiency include: fatigue, brain fog, memory problems , mus cle weaknes s , uns teady gait,
numbnes s , tingling, depres s ion, migraines /headaches and low blood pres s ure.
Xanthurenate
Xanthurenate (als o known as xanthurenic acid) is a functional marker of vitamin B6 (als o known as pyridoxine). Vitamin B6 is
a critical co-factor to over 100 important reactions that occur in the human body and is s tored in the highes t concentrations
in mus cle tis s ue. Tryptophan is readily converted to NAD by the liver. One of the s teps in this pathway requires B6. When
there is ins ufficient B6, xanthurenate is made ins tead.
Not only is xanthurenate an indicator of a lack of B6, it is als o harmful to the human body. It complexes with ins ulin and
decreas es ins ulin s ens itivity. In fact, rats fed xanthurenate will actually develop diabetes becaus e of the effects on ins ulin. If
xanthurenate levels are elevated, B6 s upplementation may be cons idered. Food high in B6 include turkey breas t, gras s -fed
beef, pinto beans , avocado, pis tachios , chicken, s es ame and s unflower s eeds .
While there is always s ome tryptophan going down the kynurenine pathway towards NAD (and pos s ibly xanthurenate), this
proces s is up-regulated by inflammation, es trogen and cortis ol. If levels of es trogen or cortis ol are high, it may exacerbate
xanthurenate elevations and increas e the need for B6.
Xanthurenate can als o bind to iron and create a complex that increas es DNA oxidative damage res ulting in higher 8-OHdG
levels . If both markers are elevated, there is likely an antioxidant ins ufficiency.
Pyroglutamate
Pyroglutamate (als o known as pyroglutamic acid) is a functional marker of glutathione deficiency. Pyroglutamate is a s tep in
the production/recycling of glutathione. If the body cannot convert pyroglutamate forward, it will s how up elevated in the
urine. High pyroglutamate is an es tablis hed marker for glutathione deficiency.
Glutathione is one of the mos t potent anti-oxidants in the human body. It is es pecially important in getting rid of toxins ,
including the reactive quinone s pecies formed by 4-OH-E1 and 4-OH-E2. This reactive s pecies can damage DNA if not
detoxified by either methylation or glutathione.
Some have reported that low pyroglutamate may als o be indicative of a need for glutathione; however, this is not es tablis hed
in the s cientific literature.
Neurotransmitter Metabolites
The neurotrans mitters dopamine, norepinephrine and s erotonin are important for human health. Meas uring
neurotrans mitters directly (direct tes ting of s erotonin, for example) is difficult becaus e of their ins tability and their urinary
meas urements are controvers ial with res pect to how well they reflect the body’s levels of thes e neuro-hormones . Each of
thes e three neurotrans mitters can be as s es s ed indirectly by meas uring their urine metabolites . While thes e metabolites are
not a perfect reflection of what’s going on in the brain, the s cientific literature does affirm their us e for a good
repres entation of overall levels of thes e neurotrans mitters .
Homovanillate (HVA)
Homovanillate (als o known as HVA) is the primary metabolite of dopamine, a brain and adrenal neurotrans mitter that comes
from tyros ine (with BH4 and iron as co-factors ) and goes on to create norepinephrine (noradrenaline) and epinephrine
(adrenaline).
Low levels of HVA can be due to low levels of dopamine or poor convers ion of dopamine to HVA. The latter may be due to
ins ufficient levels of SAM, Magnes ium, FAD and NAD which are needed to metabolize dopamine. Low circulating dopamine
may be due to ins ufficient BH4, iron or tyros ine. It may als o be s een when adrenal function is generally low. Low dopamine
levels may be as s ociated with addictions , cravings and pleas ure s eeking (to boos t levels ) in addition to s leepines s ,
impuls ivity, tremors , les s motivation, fatigue and low mood.
Elevated HVA may be caus ed by generally increas ed adrenal hormone output or becaus e of a copper or vitamin C deficiency
(which are needed for dopamine convers ion to norepinephrine). Elevations may als o be caus ed by a number of medications
or s upplements including: MAO inhibitors , quercetin, tyros ine, DL-phenylalanine (DLPA), L-dopa, macuna, dopamine
medication (Levodopa, Sinemet, Methyldopa), SNRI medication (Wellbutrin), tricyclic antidepres s ants , amphetamines , appetite
s uppres s ants , and caffeine. Bananas als o contain dopamine. Elevated dopamine may be as s ociated with los s of memory,
ins omnia, agitation, hyperactivity, mania, hyper-focus , high s tres s and anxiety as well as addictions , cravings and pleas ure
s eeking (to maintain high levels ).
Vanilmandelate (VMA)
Vanilmandelate (als o known as VMA) is the primary metabolite of norepinephrine and epinephrine (adrenaline). The adrenal
gland makes cortis ol and DHEA as well as norepinephrine and epinephrine. When adrenal hormone output is generally low,
VMA levels may be low. If HVA levels are s ignificantly higher than VMA, there may be a convers ion problem from dopamine to
norepinephrine. This cas e can be caus ed by a copper or vitamin C deficiency. The enzymes COMT (methylation) and MAO are
needed to make VMA from norepinephrine. If thes e enzymes are not working properly, VMA may be low when circulating
norepinephrine and/or epinephrine are not low. Low levels of norepinephrine and epinephrine may be as s ociated with
addictions , cravings , fatigue, low blood pres s ure, low mus cle tone, intolerance to exercis e, depres s ion, los s of alertnes s .
When the body is under phys ical or ps ychological s tres s , VMA levels may increas e. Becaus e dopamine gets converted to
norepinephrine and ultimately to VMA, the lis t of medications and s upplements that increas e HVA may als o increas e VMA.
Elevated levels may be as s ociated with feeling s tres s ed, aggres s ion, violence, impatience, anxiety, panic, worry, ins omnia,
paranoia, increas ed tingling/burning, los s of memory, pain s ens itivity, high blood pres s ure and heart palpitations .
If VMA and HVA are both extremely high, it may be neces s ary to rule out a neuroblas tic tumor.
5-Hydroxyindoleacetate (5HIAA)
5-Hydroxyindoleacetate (als o known as 5HIAA) is the primary metabolite of s erotonin. Serotonin is often thought of as the
“antidepres s ant” neurotrans mitter (becaus e common antidepres s ants aim to increas e levels ) however it is important to note
that 90% is made in the gut and jus t 1% in the brain. In the gut, s erotonin is required for gut motility and activates s mooth
mus cle activity. In the brain, the dors al raphe nucleus (DRN) in the brain s tem contains the larges t s erotonergic nucleus .
There is als o a large portion of s erotonin innervation in the forebrain (cerebrum, thalamus , hypothalamus , pituitary and
limbic s ys tem). Approximately 40% of the DRN contains es trogen receptors demons trating the tight relations hip es trogen has
with s erotonin and the brain. The Es trogen Receptor Beta (ERb) upregulates mRNA of tryptophan hydroxylas e which is the
rate limiting s tep to making 5-HTP (a precurs or to s erotonin). If es trogen is low, it’s pos s ible les s 5-HTP will be made.
The patient has low values of 5HIAA. Low 5HIAA implies decreased serotonin production/turnover. When levels
of serotonin are low, mood disorders like depression may be more likely. Serotonin may be low due to a lack of
available precursors (tryptophan or 5-HTP) or due to the excessive metabolism of the tryptophan down the
kynurenine pathway. High levels of estrogen, cortisol or inflammation push tryptophan away from serotonin and
towards the kynurenine pathway. While not common, it is also possible that serotonin levels are adequate, but
serotonin is not being properly metabolized to 5HIAA by the enzyme MAO (monoamine oxidase).
Melatonin (measured as 6-OHMS)

Melatonin is not technically an adrenal or s ex hormone however it is highly involved in the entire endocrine s ys tem. It is
made in s mall amounts in the pineal gland in res pons e to darknes s and s timulated by Melanocyte Stimulating Hormone
(MSH). A low MSH is as s ociated with ins omnia, an increas ed perception of pain, and mold expos ure. Pineal melatonin
(melatonin is als o made in s ignificant quantities in the gut) is as s ociated with the circadian rhythm of all hormones (including
female hormone releas e). It is als o made in s mall amounts in the bone marrow, lymphocytes , epithelial cells and mas t cells .
Studies have s hown that a urine s ample collected upon waking has levels of 6-Hydroxymelatonin-s ulfate (6-OHMS) that
correlate well to the total levels of melatonin in blood s amples taken continuous ly throughout the night. The DUTCH tes t us es
the waking s ample only to tes t levels of melatonin production.
Low melatonin levels may be as s ociated with ins omnia, poor immune res pons e, cons tipation, weight gain or increas ed
appetite. Elevated melatonin is us ually caus ed by inges tion of melatonin through melatonin s upplementation or eating
melatonin-containing foods . Elevated melatonin production that is problematic is rare, but levels can be higher in patients
with Chronic Fatigue Syndrome and may be phas e s hifted (peaking later) in s ome forms of depres s ion.
8-OHdG (8-Hydroxy-2-deoxyguanosine)
8-OHdG (8-hydroxy-2-deoxyguanos ine) res ults can be s een on page 6 of the DUTCH Complete (or DUTCH Plus ) report. It is a
marker for es timating DNA damage due to oxidative s tres s (ROS creation). 8-OHdG is cons idered pro-mutagenic as it is a
biomarker for various cancer and degenerative dis eas e initiation and promotion. It can be increas ed by chronic inflammation,
increas ed cell turnover, chronic s tres s , hypertens ion, hyperglycemia/pre-diabetes /diabetes , kidney dis eas e, IBD, chronic s kin
conditions (ps orias is /eczema), depres s ion, atheros cleros is , chronic liver dis eas e, Parkins on's (increas ing levels with
wors ening s tages ), Diabetic neuropathy, COPD, bladder cancer, or ins omnia. Studies have s hown higher levels in patients
with breas t and pros tate cancers . When levels are elevated it may be prudent to eliminate or reduce any caus es and
increas e the cons umption of antioxidant containing foods and/or s upplements .
The reference range for 8-OHdG is a more aggres s ive range for Functional Medicine that puts the range limit at the 80th
percentile for each gender. A clas s ic range (average plus two s tandard deviations ) would res ult in a range of 0-6ng/mg for
women and 0-10ng/mg for men. Seeking out the caus e of oxidative s tres s may be more crucial if res ults exceed thes e
limits .
Urine Hormone Testing - General Information

What is actually meas ured in urine? In blood, mos t hormones are bound to binding proteins . A s mall fraction of the total
hormone levels are "free" and unbound s uch that they are active hormones . Thes e free hormones are not found readily in
urine except for cortis ol and cortis one (becaus e they are much more water s oluble than, for example, tes tos terone). As
s uch, free cortis ol and cortis one can be meas ured in urine and it is this meas urement that nearly all urinary cortis ol
res earch is bas ed upon. In the DUTCH Adrenal Profile the diurnal patterns of free cortis ol and cortis one are meas ured by LC-
MS/MS.
All other hormones meas ured (cortis ol metabolites , DHEA, and all s ex hormones ) are excreted in urine predominately after
the addition of a glucuronide or s ulfate group (to increas e water s olubility for excretion). As an example, Tajic (Natural
Sciences , 1968 publication) found that of the tes tos terone found in urine, 57-80% was tes tos terone-glucuronide, 14-42% was
tes tos terone-s ulfate, and negligible amounts (<1% for mos t) was free tes tos terone. The mos t likely s ource of free s ex
hormones in urine is from contamination from hormonal s upplements . To eliminate this potential, we remove free hormones
from conjugates . The glucuronides and s ulfates are then broken off of the parent hormones , and the meas urement is made.
Thes e meas urements reflect the bioavailable amount of hormone in mos t cas es as it is only the free, nonprotein-bound
fraction in blood/tis s ue that is available for phas e II metabolis m (glucuronidation and s ulfation) and s ubs equent urine
excretion.
Dis claimer: the filter paper us ed for s ample collection is des igned for blood collection, s o it is technically cons idered
"res earch only" for urine collection. Its proper us e for urine collection has been thoroughly validated.
Reference Range Determination (last updated 11.15.2017)
We aim to make the reference ranges for our DUTCH tes ts as clinically appropriate and us eful as pos s ible. This includes the
tes ting of thous ands of healthy individuals and combing through the data to exclude thos e that are not cons idered “healthy”
or “normal” with res pect to a particular hormone. As an example, we only us e a premenopaus al woman’s data for es trogen
range determination if the as s ociated proges terone res ult is within the luteal range (days 19-21 when proges terone s hould
be at its peak). We exclude women on birth control or with any conditions that may be related to es trogen production. Over
time the databas e of res ults for reference ranges has grown quite large. This has allowed us to refine s ome of the ranges
to optimize for clinical utility. The manner in which a metabolite’s range is determined can be different depending on the
nature of the metabolite. For example, it would not make clinical s ens e to tell a patient they are deficient in the carcinogenic
es trogen metabolite, 4-OH-E1 therefore the lower range limit for this metabolite is s et to zero for both men and women.
Modes tly elevated tes tos terone is as s ociated with unwanted s ymptoms in women more s o than in men, s o the high range
limit is s et at the 80th percentile in women and the 90th percentile for men. Note: the 90th percentile is defined as a res ult
higher than 90% (9 out of 10) of a healthy population.
Clas s ic reference ranges for dis eas e determination are us ually calculated by determining the average value and adding and
s ubtracting two s tandard deviations from the average, which defines 95% of the population as being “normal.” When tes ting
cortis ol, for example, thes e types of two s tandard deviation ranges are effective for determining if a patient might have
Addis on’s (very low cortis ol) or Cus hing’s (very high cortis ol) Dis eas e. Our ranges are s et more tightly to be optimally us ed
for Functional Medicine practices .
Below you will find a des cription of the range for each tes t:
Provider Notes:
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DUTCH Complete Male Sample Report 6 - 21 - 18

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Accession # 00280402

Male Sample Report

Ordering Physician: DOB: 1966-05-06 Collection Times:

Hormone Testing Summary

Key (how to read the results): Sex Hormones

See Pages 2 & 3 for a thorough breakdown of sex hormone metabolites

Total DHEA Production

Sex Hormones and Metabolites

Category Test Result Units Normal Range

ar 115 Testosterone 5α-DHT

4.0 16.0 0.50 2.20 2.0 8.0

Patient 2-OH 4-OH 16-OH

Low High QUINONE

2.80 methylation 5.90

If not detoxiﬁed, 4-OH-E1 can

Category Test Result Units Normal Range

Stress (or inﬂammation)

causes the brain to release ACTH,

Melatonin* (Waking) 1000

Total DHEA Production

Metabolized Cortisol (THF+THE)

More cortisone More cortisol

metabolites (THE) metabolites (THF)

24hr Free Cortisone 24hr Free Cortisol

Organic Acid Tests (OATs)

Category Test Result Units Normal Range

Melatonin (*measured as 6-OH-Melatonin-Sulfate) - (Urine)

Patient or Sample Comments

The status (low, normal or high?) of testosterone:

The metabolic preference for the 5a (5-alpha) or 5b (5-beta) pathway:

A potential preference for cortisol or cortisone (the inactive form):

Nutritional Organic Acids

Melatonin (measured as 6-OHMS)

Urine Hormone Testing - General Information

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