DUTCH Test: Which Tests to Order Alongside It

What the DUTCH Test Actually Measures

The DUTCH test quantifies hormone metabolites excreted in urine over a roughly 24-hour collection compressed into four or five timed filter-paper spots. This captures not just hormone levels but how the body is processing and clearing those hormones, information a single serum draw cannot provide. Precision Analytical, the test's developer, has published analytical validation data showing high correlation with 24-hour urine steroid profiles.

Sex Hormone Metabolites

The panel reports estrone (E1), estradiol (E2), and estriol (E3) alongside their downstream 2-OH, 4-OH, and 16-OH metabolites. The 2:16 hydroxyestrone ratio is used clinically by some practitioners to assess estrogen metabolism patterns, though the Endocrine Society notes that routine use of this ratio in clinical decision-making lacks definitive outcome data. A 2011 review in the Journal of Clinical Endocrinology and Metabolism examined hydroxylation pathway variation across populations.

Progesterone metabolites (pregnanetriol, pregnanediol) and testosterone metabolites (androsterone, etiocholanolone, 5a-DHT) are also quantified. In men on testosterone replacement therapy, tracking 5a-reductase and aromatase activity through these metabolites is one of the DUTCH test's most clinically useful features.

Adrenal Markers

Cortisol and cortisone are measured at four time points, producing a diurnal curve. Free cortisol is distinguished from total cortisol metabolites, allowing differentiation between cortisol production and cortisol clearance problems. DHEA metabolites (androsterone and etiocholanolone, the DHEA-specific fractions) round out the adrenal assessment.

The DUTCH Plus variant adds a saliva cortisol awakening response (CAR), a five-point morning measurement that the Endocrine Society's 2016 guideline on adrenal insufficiency identifies as a marker of hypothalamic-pituitary-adrenal axis reactivity. See Endocrine Society: Diagnosis of Adrenal Insufficiency in Adults, 2016.

Why the DUTCH Test Alone Is Not a Complete Hormone Workup

The DUTCH test is a specialized metabolite map. It does not measure binding proteins, upstream pituitary signals, thyroid function, metabolic health markers, or red cell and liver parameters. Ordering it without companion labs is like reading only chapter seven of a patient chart.

The Binding Protein Gap

Sex hormone-binding globulin (SHBG) determines how much estradiol and testosterone is biologically available. A patient can show adequate urine testosterone metabolites on the DUTCH report while having very high SHBG, leaving free testosterone clinically low. A 2013 study in the Journal of Clinical Endocrinology and Metabolism (N=2,012) demonstrated that SHBG independently predicted free testosterone below normal range in 31% of men whose total testosterone was in the normal reference interval. Serum SHBG is ordered separately and is not included in the DUTCH output.

The Pituitary Signal Gap

LH and FSH are the upstream drivers of gonadal hormone production. If estradiol or testosterone metabolites are low on the DUTCH panel, LH and FSH results reveal whether the problem is primary gonadal failure (high LH/FSH) or secondary/central hypogonadism (low or inappropriately normal LH/FSH). The DUTCH test does not measure either gonadotropin.

The Essential Companion Labs to Order With the DUTCH Test

The following framework reflects the HealthRX clinical team's ordering protocol for patients presenting with suspected hormone imbalance who are undergoing initial DUTCH testing or follow-up on an existing hormone therapy protocol.

Tier 1: Order Every Time

Serum SHBG. SHBG changes with thyroid status, insulin resistance, liver disease, and exogenous hormone use. Without it, free hormone calculations are impossible. The Endocrine Society's 2018 testosterone therapy guideline explicitly recommends measuring SHBG when total testosterone is borderline, to calculate free testosterone.

TSH with reflex free T4. Thyroid dysfunction alters SHBG, changes cortisol clearance rates, and produces symptoms (fatigue, weight change, mood disruption) that overlap completely with sex hormone imbalance. The USPSTF has not mandated universal thyroid screening, but the American Thyroid Association's 2012 guideline recommends TSH testing for patients with symptoms consistent with thyroid dysfunction.

Fasting insulin and fasting glucose. Insulin resistance suppresses SHBG, raises androgens in women, and blunts adrenal recovery. The American Diabetes Association's 2024 Standards of Care recommend fasting plasma glucose and, when available, fasting insulin for insulin resistance assessment in at-risk patients. See ADA Standards of Medical Care in Diabetes, 2024.

Serum DHEA-S. The DUTCH test reports DHEA metabolites in urine, but serum DHEA-S is the gold-standard measure of adrenal androgen reserve. Both values together allow a clinician to distinguish between impaired production and impaired conversion or metabolism. AACE guidelines on adrenal disease reference serum DHEA-S as the standard biomarker for adrenal androgen output.

Tier 2: Order Based on Clinical Context

Serum LH and FSH. Required for anyone with low sex hormone metabolites on DUTCH, anyone considering fertility, and all patients stopping exogenous hormones to assess recovery of the hypothalamic-pituitary-gonadal (HPG) axis. The Endocrine Society's 2010 guideline on female hypogonadism identifies LH and FSH as essential for distinguishing primary from central causes.

Serum estradiol (E2). Urine estradiol metabolites and serum estradiol are not interchangeable. Serum E2 reflects circulating hormone; urine metabolites reflect processing. In women on oral estrogen, first-pass liver metabolism elevates urine metabolites disproportionately compared with transdermal routes. A concurrent serum E2 anchors interpretation.

Complete blood count (CBC). Testosterone therapy raises hematocrit; the Endocrine Society's 2018 TRT guideline recommends holding or reducing testosterone if hematocrit exceeds 54%. Baseline and follow-up CBC is explicitly recommended in that guideline.

Comprehensive metabolic panel (CMP). Liver enzymes (AST, ALT) matter because the liver drives estrogen hydroxylation and sulfation. Elevated transaminases can explain aberrant DUTCH metabolite ratios. Creatinine and BUN matter for patients on any concentrated supplement regimen.

Lipid panel. Estrogen, testosterone, and cortisol all affect lipid metabolism. The American Heart Association's 2019 guideline on cardiovascular risk management identifies dyslipidemia as a modifiable risk factor in patients on hormone therapy. See AHA/ACC 2019 Guideline on Primary Prevention of Cardiovascular Disease.

Morning serum cortisol (8 a.m.). When the DUTCH diurnal curve shows a flat or blunted pattern, a single 8 a.m. Serum cortisol confirms whether true cortisol insufficiency is present before any treatment escalation. The Endocrine Society's 2016 adrenal insufficiency guideline sets a serum cortisol of <3 mcg/dL as highly suggestive of adrenal insufficiency and >18 mcg/dL as likely sufficient. See the guideline here.

Tier 3: Specialty or Follow-Up Panels

Prolactin. Hyperprolactinemia suppresses GnRH, reducing LH, FSH, and downstream sex hormones. Any patient with low DUTCH sex hormone metabolites and no obvious cause should have prolactin checked once.

IGF-1. Growth hormone deficiency produces fatigue, body composition changes, and impaired sleep, all symptoms that overlap with adrenal or sex hormone dysfunction. IGF-1 is the standard screening marker, not growth hormone itself.

24-hour urine free cortisol. When the DUTCH cortisol metabolite pattern suggests possible Cushing syndrome, a 24-hour urine free cortisol is the next diagnostic step per the Endocrine Society's 2008 Cushing syndrome guideline, which recommends at least two confirmatory tests. Endocrine Society Cushing Syndrome Guideline, 2008.

What Normal DUTCH Test Ranges Look Like

"Normal" on a DUTCH report is reference-interval-based, drawn from Precision Analytical's proprietary population database stratified by sex, menopausal status, and collection time. These are not universal guideline-defined ranges like serum TSH or fasting glucose.

Cortisol Pattern Norms

Free cortisol across the four collection points should show a clear diurnal decline: highest in the morning first void and lowest in the evening. Total cortisol metabolites reflect overall production. A flat curve (all four points in low-normal range with no morning peak) points to HPA axis hypo-reactivity rather than frank adrenal insufficiency. An elevated evening free cortisol alongside normal morning levels is a common pattern in chronic stress.

Sex Hormone Metabolite Norms

For premenopausal women, estrogen metabolites shift across the menstrual cycle; the DUTCH test is ideally collected on days 19 to 22 to capture luteal-phase levels. Precision Analytical's published reference ranges show luteal-phase estradiol metabolite targets roughly 2.0 to 7.0 mcg/mg creatinine for estradiol in premenopausal women, though these values carry analytical context and should not be used interchangeably with serum E2 in pg/mL.

Testosterone metabolites in men should reflect androsterone and etiocholanolone outputs consistent with a serum total testosterone of 400 to 900 ng/dL. The Endocrine Society defines male hypogonadism as a morning total testosterone below 300 ng/dL on two separate measurements.

Interpreting Ratios

The 2-OH:16-OH hydroxyestrone ratio and the 2-methoxy:2-OH ratio (reflecting COMT enzyme activity) appear on many DUTCH reports. These ratios are hypothesis-generating, not diagnostic. A 2012 review in Cancer Epidemiology, Biomarkers and Prevention noted that estrogen metabolite ratios in urine are associated with breast cancer risk in observational data but do not yet have sufficient evidence to guide clinical intervention.

How to Raise Low Values on the DUTCH Test

Low sex hormone metabolites on DUTCH generally reflect either low production or excess clearance. The clinical path depends on which companion labs are also abnormal.

Low Estrogen Metabolites

In menopausal women, low estrogen metabolites combined with low serum E2 and elevated FSH (>40 mIU/mL) confirm ovarian estrogen loss. The NAMS 2022 Menopause Hormone Therapy Position Statement supports transdermal estradiol at 0.05 to 0.1 mg/day as a first-line approach. See the NAMS 2022 position statement here.

Transdermal versus oral estrogen produces markedly different DUTCH metabolite patterns. Oral estrogen undergoes first-pass liver conversion, generating higher 16-OH metabolites relative to 2-OH metabolites compared with the same serum E2 achieved transdermally.

Low Cortisol Metabolites

A flat, low cortisol pattern on DUTCH with a confirmed low 8 a.m. Serum cortisol warrants formal ACTH stimulation testing before any treatment. The Endocrine Society does not recommend empiric adrenal support supplements as a first-line response to a low DUTCH cortisol curve without confirmatory biochemistry. Endocrine Society guideline, 2016.

Lifestyle factors with documented cortisol effects include sleep, caloric restriction, and chronic exercise overreaching. A 2018 review in Psychoneuroendocrinology (N=200 across included studies) found that sleep restriction below six hours per night elevated evening cortisol and flattened the morning awakening response.

How to Lower Elevated Values on the DUTCH Test

Elevated cortisol metabolites or elevated androgen metabolites each have separate diagnostic trees.

High Cortisol Metabolites

Elevated total cortisol metabolites with a normal diurnal curve most often reflect high cortisol production driven by chronic psychological stress, obesity, or glucocorticoid medication use. When the pattern meets criteria for suspected Cushing syndrome (elevated late-night salivary cortisol, loss of diurnal rhythm, clinical features), the Endocrine Society's 2008 guideline recommends 1 mg overnight dexamethasone suppression testing as a next step, with a cutoff of <1.8 mcg/dL to rule out the diagnosis. Endocrine Society Cushing Guideline, 2008.

High Androgen Metabolites in Women

Elevated DHEA metabolites and testosterone metabolites in premenopausal women suggest either polycystic ovary syndrome (PCOS) or adrenal androgen excess. The Endocrine Society's 2013 PCOS guideline recommends measuring serum total testosterone, free testosterone (or calculated free testosterone using SHBG), and DHEA-S alongside LH:FSH ratio. Endocrine Society PCOS Guideline, 2013. An LH:FSH ratio >2:1 with elevated androgens and polycystic ovarian morphology on ultrasound supports a PCOS diagnosis.

High Estrogen Metabolites in Men

In men on testosterone replacement therapy, high estrogen metabolites on DUTCH combined with elevated serum E2 (above 40 pg/mL by sensitive assay) may warrant aromatase inhibitor consideration. The Endocrine Society's TRT guideline notes that estradiol management in TRT patients remains an area of clinical uncertainty; aromatase inhibitors are not FDA-approved for this indication in men, and use is off-label. See the 2018 Endocrine Society TRT guideline.

Retesting and Monitoring Intervals

After an initial DUTCH test, a 90-day retest is the minimum clinically useful interval when any hormone therapy has been initiated or adjusted. Most hormone therapies require 60 to 90 days to reach steady-state metabolite output. Retesting sooner produces data that reflects a transitional state rather than the achieved therapeutic effect.

For patients on stable, long-term hormone therapy with no symptoms, a 180-day (six-month) retest interval paired with concurrent serum SHBG, E2 or testosterone, and CBC (if on TRT) provides adequate safety monitoring without excessive testing frequency.

The Endocrine Society's 2018 TRT guideline recommends assessing testosterone levels, hematocrit, and symptom response at three and six months after initiation, then annually thereafter. Endocrine Society TRT Guideline, 2018.