The DUTCH Test: Complete Hormone & Adrenal Mapping

Beyond Blood Draws and Saliva Swabs

A serum estradiol level tells you how much estrogen is circulating in the blood at the moment the needle enters the vein. It tells you nothing about how that estrogen is being metabolized — whether it is traveling down the protective 2-hydroxy pathway or the genotoxic 4-hydroxy pathway that damages DNA. A morning salivary cortisol tells you free cortisol at one time point. It misses total cortisol production, cortisone patterns, the cortisol awakening response, and metabolized cortisol output.

The DUTCH test — Dried Urine Test for Comprehensive Hormones — created by Mark Newman at Precision Analytical, solves these blind spots. By measuring hormone metabolites in dried urine collected across a full day, it maps how the body produces, processes, and eliminates hormones. In the IFM framework, hormonal and neurotransmitter imbalance is one of the seven core clinical imbalances. The DUTCH provides the most complete single-test assessment of this node.

Collection and Methodology

The patient collects four to five urine samples on filter paper strips over a 24-hour period: evening before bed, overnight (if awake), waking, two hours after waking (captures the cortisol awakening response), and one more evening sample. The dried strips are mailed to the lab. Results include sex hormones and their metabolites, adrenal hormones with diurnal patterns, melatonin, and — in the DUTCH Plus — organic acid markers for neurotransmitter and nutrient status.

Estrogen Metabolism: The Cancer Risk Pathway

This is the section of the DUTCH that oncologists, integrative practitioners, and women’s health specialists pay closest attention to. Estrogen metabolism is a two-phase hepatic process, and the pathway it takes determines whether estrogen is protective or carcinogenic.

Phase I: The Three Hydroxylation Pathways

The liver’s cytochrome P450 enzymes hydroxylate estrogens (estrone and estradiol) at three positions:

2-Hydroxy estrogen (2-OH) — produced by CYP1A1 and CYP1A2. This is the favorable pathway. 2-OH estrogens have weak estrogenic activity and are considered antiproliferative. Cruciferous vegetables, DIM, I3C, and exercise upregulate this pathway.

4-Hydroxy estrogen (4-OH) — produced by CYP1B1. This is the danger pathway. 4-OH estrogens form unstable quinones that directly damage DNA through depurination — creating mutations that initiate cancer. CYP1B1 is upregulated by environmental toxins, obesity, and inflammation. If 4-OH is high on the DUTCH, you are seeing active genotoxic estrogen metabolism.

16-Hydroxy estrogen (16-OH) — produced by CYP3A4. This pathway is proliferative — 16-OH estrogens stimulate cell growth. Moderately elevated 16-OH increases estrogenic effects. Extremely high 16-OH is seen in obesity (adipose tissue favors this pathway) and hypothyroidism.

The 2-OH to 16-OH ratio should be above 2.0. Below that, the balance tips toward proliferative and potentially carcinogenic estrogen metabolism.

Phase II: Methylation — The Safety Net

Here is where the DUTCH reveals something no other hormone test shows. Even if 4-OH estrogen is elevated, if Phase II methylation is robust, the 4-OH gets rapidly methylated into 4-methoxy estrogen — which is inert and safely excreted. The DUTCH reports 2-methoxy estrone (2-MeOE1) as a marker of methylation capacity.

The critical clinical scenario: 4-OH high AND methylation poor (low 2-MeOE1 relative to 2-OH). This patient has the highest risk — genotoxic estrogen metabolites accumulating without adequate methylation to neutralize them. This demands aggressive intervention.

Interventions to Modify Estrogen Metabolism

DIM (diindolylmethane): 100-200mg daily. The active metabolite of indole-3-carbinol from cruciferous vegetables. Shifts Phase I metabolism toward the 2-OH pathway and away from 4-OH and 16-OH. Start at 100mg — some patients experience estrogen-withdrawal symptoms as metabolism shifts.

I3C (indole-3-carbinol): 200-400mg daily. The precursor to DIM. Some clinicians prefer I3C because it supports multiple estrogen metabolism pathways, though it requires stomach acid for conversion.

Sulforaphane: From broccoli sprout extract or fresh broccoli sprouts. Induces Phase II detoxification enzymes (NQO1, glutathione transferases) that neutralize quinone metabolites. Also induces CYP1A2 (favorable 2-OH pathway).

Calcium d-glucarate: 500mg twice daily. Inhibits beta-glucuronidase, preventing estrogen reabsorption in the gut. Works at the GI elimination step.

Methylation support: Methylfolate (400-1000mcg), methyl-B12 (1000-5000mcg), SAMe (200-400mg), magnesium (cofactor for COMT). COMT is the enzyme that methylates catechol estrogens — slow COMT polymorphisms (Val/Met or Met/Met) mean slower 4-OH clearance.

Ground flaxseed: 2 tablespoons daily. Lignans bind estrogen receptors and promote favorable metabolism. SDG lignans from flax specifically reduce 16-OH production.

Progesterone Metabolites

The DUTCH measures a-pregnanediol and b-pregnanediol — the metabolic end products of progesterone. Serum progesterone is a single snapshot. DUTCH metabolites reflect total progesterone production over the collection period.

Low progesterone metabolites in the luteal phase (cycle days 19-22) confirm anovulation or inadequate corpus luteum function — the most common cause of estrogen dominance, PMS, and PMDD. One of progesterone’s metabolites, allopregnanolone, is a potent GABA-A receptor modulator — essentially the body’s endogenous anxiolytic. Women with low allopregnanolone experience premenstrual anxiety, insomnia, and mood destabilization because they lose this natural GABA support in the late luteal phase.

Support for low progesterone: vitex (chasteberry, 400mg AM — increases luteinizing hormone pulsatility), vitamin B6 as P5P (50-100mg — supports corpus luteum function), vitamin C (750mg — shown to increase progesterone in luteal phase defect), and if botanical support is insufficient, bioidentical progesterone (oral, topical, or vaginal, dosed in the luteal phase).

Androgen Metabolites

The DUTCH reports DHEA-S, testosterone, and the downstream metabolites that reveal enzyme activity patterns. The key clinical insight is 5-alpha-reductase activity — the enzyme that converts testosterone to DHT (dihydrotestosterone).

5-alpha pathway: Testosterone to 5a-DHT to 5a-androstanediol. High activity here means more DHT production — clinically manifesting as hair loss (androgenic alopecia), acne, oily skin, and in men, prostate enlargement. Saw palmetto (320mg/day), zinc (30-50mg), green tea (EGCG), and reishi mushroom inhibit 5-alpha-reductase.

5-beta pathway: Testosterone to 5b-metabolites. This is the clearance pathway — metabolic inactivation and excretion. Low 5-beta activity means testosterone persists longer.

In women, high total androgens with elevated 5a-reductase activity is the DUTCH pattern of PCOS. The upstream driver is usually insulin resistance — insulin stimulates ovarian theca cells to produce androgens. Address insulin first (berberine 500mg three times daily, inositol — myo-inositol 4g plus d-chiro-inositol 100mg daily, exercise, low-glycemic diet), then modulate androgens with DIM, spearmint tea (two cups daily — clinically shown to reduce free testosterone), and saw palmetto.

The Adrenal Map: Cortisol and Cortisone

Diurnal Cortisol Pattern

The DUTCH plots free cortisol at four time points: waking, morning, afternoon, and night. A healthy pattern shows high morning cortisol that progressively declines through the day, reaching its nadir at night. This rhythm drives alertness, energy, immune cycling, and sleep onset.

Flat patterns — low morning, low evening, no curve — indicate HPA axis dysfunction (commonly called adrenal fatigue, though the adrenals themselves are not fatigued; it is the hypothalamic-pituitary signaling that is dysregulated). This pattern is seen in burnout, chronic stress, PTSD, and chronic illness.

Inverted patterns — low morning, elevated evening cortisol — produce the “tired but wired” presentation. The patient cannot wake up in the morning and cannot fall asleep at night.

The Cortisol Awakening Response (CAR)

The DUTCH Plus adds a fifth sample 30 minutes after waking. Cortisol should spike 50-75% above the waking baseline in this first half hour — the CAR. This spike activates the brain for the day’s cognitive demands.

A blunted or absent CAR (less than 20% rise) is associated with HPA axis exhaustion, PTSD, depression, and chronic fatigue. An exaggerated CAR (more than 100% rise) suggests anticipatory stress, anxiety disorders, or job strain. The CAR is one of the most reproducible and clinically useful markers of HPA axis function.

Metabolized Cortisol: The Hidden Production

This is the DUTCH insight that overturns many misdiagnoses. Free cortisol (what saliva tests measure) represents only 1-3% of total cortisol output. The vast majority is metabolized in the liver (THE, THF, 5a-THF) and excreted in urine.

A patient can have normal free cortisol but massively elevated metabolized cortisol — meaning they are producing large amounts of cortisol but clearing it rapidly. Salivary testing would call them “normal.” The DUTCH reveals they are in a high-production, high-clearance state — often driven by obesity (adipose tissue expresses 11-beta-HSD1, which regenerates cortisol from cortisone), liver upregulation, or thyroid excess.

Conversely, low free cortisol with low metabolized cortisol confirms true hypocortisolism — the adrenals genuinely are not producing enough.

Cortisol-to-Cortisone Ratio

Cortisone is the inactive storage form of cortisol. The enzyme 11-beta-HSD1 converts cortisone to cortisol (activation) in tissues, while 11-beta-HSD2 converts cortisol to cortisone (inactivation), primarily in the kidneys.

When the DUTCH shows cortisone consistently higher than cortisol throughout the day, 11-beta-HSD2 is dominant — the body is deactivating cortisol faster than it can be replaced. The patient may have adequate total production but insufficient active cortisol at the tissue level. Licorice root (glycyrrhizin inhibits 11-beta-HSD2, prolonging cortisol’s half-life) can be therapeutic here — but monitor blood pressure, as this same mechanism can cause hypertension with excessive use.

Melatonin

The DUTCH measures 6-hydroxy-melatonin-sulfate, the primary urinary metabolite of melatonin. Low levels indicate insufficient melatonin production — affecting sleep onset, antioxidant protection (melatonin is a potent free radical scavenger), and immune modulation.

Low melatonin is common in shift workers, blue-light exposure before bed, aging (pineal calcification), and beta-blocker users (beta-blockers suppress melatonin production — this is why they cause insomnia). Intervention: sleep hygiene, blue-light blocking after sunset, and melatonin supplementation (0.5-3mg at bedtime for physiologic dosing; 5-20mg for antioxidant or immune purposes).

Organic Acid Markers (DUTCH Plus)

The DUTCH Plus adds a subset of organic acid markers that overlap with the full OAT but provide targeted hormone-relevant data:

HVA and VMA: Dopamine and norepinephrine metabolites — assess catecholamine status alongside adrenal hormones. Low dopamine with high cortisol = burnout pattern.

Methylmalonate: Functional B12 status — methylation capacity directly affects hormone metabolism.

Xanthurenate and kynurenate: B6 status and neuroinflammation. B6 as P5P is a cofactor for over 100 enzyme reactions including hormone synthesis.

8-OHdG (8-hydroxy-2-deoxyguanosine): Oxidative DNA damage marker. Elevated 8-OHdG means free radicals are damaging DNA — increases cancer risk and accelerates aging. This marker, unique to the DUTCH, adds an oxidative stress dimension to hormonal assessment.

Clinical Patterns and Protocols

PCOS: High androgens, elevated 5a-reductase metabolites, often with elevated metabolized cortisol (HPA-HPG axis crosstalk) and poor estrogen clearance. Address insulin resistance first, then modulate androgens and estrogen metabolism.

Estrogen dominance: High estrogens relative to progesterone, poor 2-OH to 16-OH ratio, high 4-OH with poor methylation, and possibly elevated beta-glucuronidase on GI-MAP. This is not just a hormone problem — it is a liver, gut, and methylation problem.

Adrenal dysfunction stages: High cortisol with preserved rhythm (Stage 1 — alarm). High cortisol with disrupted rhythm (Stage 2 — resistance). Low cortisol with flat rhythm (Stage 3 — exhaustion). Each stage requires a different intervention — adaptogens for Stage 1-2 (ashwagandha 300-600mg, rhodiola 200-400mg), glandular support and cortisol-sparing strategies for Stage 3.

Perimenopause/menopause: The DUTCH tracks declining estrogen and progesterone production while showing whether existing hormones are metabolized safely. Essential before initiating hormone replacement therapy — ensure the metabolism pathways are favorable before adding substrate.

The DUTCH is not a standalone test. It is the hormonal layer in a comprehensive functional medicine workup that includes GI-MAP (gut health), OAT (metabolic function), comprehensive blood panel (thyroid, metabolic, inflammatory markers), and targeted genomic testing (COMT, CYP1B1, MTHFR). Each test informs the others. Together, they create the complete picture that the IFM Matrix demands.