Detailed Test Information
DUTCH PLUS
Key Advantages
- Takes hormone testing to a whole new level: Dutch Complete™ + Cortisol Awakening Response (CAR)
- Convenient at-home, salivary and dried urine collection methods
- Represents an entire day’s hormone production during peak Luteal phase
- Includes metabolites of Oestrogens, Androgens, Progesterone, Cortisol, Melatonin, Adrenaline, Noradrenaline and 8-OHdG as well as organic acid markers for neurotransmitters and nutrient metabolism
- Includes the diurnal pattern of Free Cortisol and Cortisone and metabolites, with Cortisol Awakening Response (CAR)
- Optional nighttime Insomnia Cortisol measurement
test background
The DUTCH Plus® is a comprehensive analysis combining the DUTCH Complete™ PLUS a closer look into adrenal function with Cortisol Awakening Response (CAR). The DUTCH Plus® provides a comprehensive analysis of the major sex hormones and their metabolites, adrenal hormones, and some key nutrients involved in sex hormone metabolism, along with the evaluation of Melatonin, Dopamine, and oxidative stress.
The DUTCH Plus® provides practitioners and their patients with detailed information, putting a spotlight on areas of imbalance or concern, and helps to guide towards more positive treatment outcomes.
HOW DO YOU COLLECT THE DUTCH Plus® TEST?
The DUTCH Plus® uses 4 dried urine samples and 5 saliva samples. These samples are collected over the course of 24-hours, from waking to bedtime.
What can the DUTCH Plus® tell us that the DUTCH Complete™
and other adrenal tests cannot?
Even though a patient may have “normal” free cortisol levels throughout the day, that doesn’t always mean everything is functioning properly. The graph below shows two good examples. A blunted or exaggerated CAR can appear, even when single samples return “normal” results. The HPA axis might not be appropriately responding when faced with a stressor, even when cortisol levels are fluctuating nicely throughout the day. The “stress response” of waking, allows us to test the HPA axis in a way that has been independently correlated to clinical outcomes and cannot be assessed by other cortisol tests on the market.
DAILY FREE CORTISOL AWAKENING RESPONSE
CLINICAL VALUE
Improved Accuracy
Urinary collection improves accuracy for progesterone and oestrogen markers when compared to saliva and blood. All Precision Analytical testing methods go through a rigorous and ongoing validation process to verify accuracy, precision, recovery, linearity, etc.
Salivary and Urinary Cortisol Analysis
Salivary samples allows for accurate CAR measurement. This in combination with urinary cortisol and cortisone metabolites gives a more in-depth insight into adrenal function.
Analysis of Hormonal Imbalances
The DUTCH Plus® is a comprehensive panel inclusive of hormones and their metabolites for additional insight into hormonal activity (sex and stress hormones) throughout the body.
Effective HRT Monitoring
DUTCH Plus® testing was specifically made to be optimally effective for most forms of hormone replacement therapy. Unique methods are used for improved monitoring of oral progesterone and vaginal hormones.
Includes Organic Acids
The DUTCH Plus® allows for more in-depth analysis into neurotransmitter metabolites and nutritional cofactors in relation to hormonal balance, detoxification and inflammation.
KEY ASSESSMENTS INCLUDED
- Diurnal Cortisol pattern including CAR
- 10 x Oestrogens and metabolites (including E1, E2, E3, 2-OH-E1, 4-OH-E1, 16-OH-E1, 2-methoxy-E1)
- 8 x Androgens and metabolites (including Testosterone, DHT and DHEA-S)
- 2 x Progesterone metabolites (α-Pregnanediol and β-Pregnanediol)
- 4 x Cortisol and Cortisone markers
- 4 x Cortisol and Cortisone metabolites
- Melatonin
- 8-OHdG (oxidative stress)
- 3 x Neurotransmitter metabolites (HVA, VMA, Quinolinate)
- 6 x Nutritional Organic Acids (b-Hydroxyisovalerate, Indican, MMA, Xanthurenate, Kynurenate, Pyroglutamate)
What is the Cortisol Awakening Response and how do we test for it?
When we open our eyes upon waking, cortisol levels naturally begin to rise by an average of 50%. Cortisol levels increase sharply within 30 minutes after waking. By 60 minutes after waking, cortisol levels have peaked and begin to decline. Measuring this rise and fall of cortisol levels at waking can be used as a “mini stress test”.
Research shows that the size of this increase correlates with HPA-axis function, even if the sample measurements are all within range. Cortisol testing using saliva swabs upon waking, 30 minutes after waking and 60 minutes after waking, allows accurate assessment of a patient’s Cortisol Awakening Response.
A low CAR can be a result of an underactive HPA axis, excessive psychological burnout, seasonal affective disorder (SAD), sleep apnoea or poor sleep in general, PTSD, chronic fatigue and/or chronic pain. A decreased CAR has also been associated with systemic hypertension, functional GI diseases, postpartum depression, and autoimmune diseases.
An elevated CAR can be a result of an over-reactive HPA axis, ongoing job-related stress (anticipatory stress for the day), glycaemic dysregulation, pain (i.e. waking with painful joints or a migraine), and general depression (not SAD). A recent study showed that neither the waking nor post-waking cortisol results correlated to Major Depressive Disorder, but the CAR calculation (the change between the first two samples) did. This measurement of the response to waking has independent clinical value showing dysfunction that may be hidden by current testing options.
What is the Cortisol Awakening Response and how do we test for it?
A true CAR assessment requires salivary samples to be collected on waking (without delay), and twice more, at 30 minutes after waking and 60 minutes after waking. These specifically timed collections are difficult and impractical with urine, blood and traditional salivary options.
The DUTCH Plus® uses specialty, FDA-approved, and patented collection devices called Salivettes™. Salivettes™ are specifically made for testing cortisol when timing needs to be precise and are used in nearly all of the published CAR studies. The small synthetic cotton swab can be quickly saturated with saliva, providing a very fast and simple collection. Unfortunately for labs using saliva to test reproductive hormones, they are not a viable option as the swabs cannot be used when testing progesterone.
The DUTCH Plus® offers the most accurate salivary cortisol sampling with Salivette™ collection with LC-MS/MS analysis, providing an unparalleled clinical tool combining salivary cortisol with the extensive urine metabolites from DUTCH Complete™.
RELATED TESTS
- DUTCH CYCLE MAPPING™
- DUTCH CYCLE MAPPING™ PLUS
- DUTCH COMPLETE™
- DUTCH ADRENAL
RESOURCES
Videos
Resources
FAQs
Test Pricing
References
Videos
Introduction to DUTCH Plus
DUTCH Plus Report Overview
DUTCH Plus Collection Guide
Resources
FAQs
For patients with a cycle, the mid-luteal phase is the point in the cycle where both Progesterone and Estrogen are being produced in substantial amounts. This provides an opportunity to assess the balance and sufficiency of these hormones.
Therefore, the DUTCH Sex Hormone test results are aimed at providing insights in this window. Despite typical textbook references stating the average mid-luteal point to be on day 21 of the cycle, individual cycles may vary from this.
For this reason, it can be more useful to count 7 days forward from ovulation or 7 days back from expected menses (in patients with regular cycles), or better still test for the Luteinising Hormone (LH) surge, to guide a more precise indication of which day to complete the test (for maximum insights).
If the patient is menopausal or collects outside the luteal phase, there are additional reference ranges provided on page 2 in the report.
If the patient has an irregular, shorter or longer cycle, see when to collect.
Some practitioners may test at other times in situations where symptoms are present during different phases of the cycle (or if using DUTCH Cycle Mapping Plus).
Cycling patients
Mid-luteal phase – which may be: 5-7 days after ovulation (consider confirming this with LH strips), 7 days before the expected period.
Menopausal patients
Collect any day
Irregular cycles
See ‘Is my patient ovulating?’
Male patients
Collect any day
Therefore, the DUTCH Sex Hormone test results are aimed at providing insights in this window. Despite typical textbook references stating the average mid-luteal point to be on day 21 of the cycle, individual cycles may vary from this.
For this reason, it can be more useful to count 7 days forward from ovulation or 7 days back from expected menses (in patients with regular cycles), or better still test for the Luteinising Hormone (LH) surge, to guide a more precise indication of which day to complete the test (for maximum insights).
If the patient is menopausal or collects outside the luteal phase, there are additional reference ranges provided on page 2 in the report.
If the patient has an irregular, shorter or longer cycle, see when to collect.
Some practitioners may test at other times in situations where symptoms are present during different phases of the cycle (or if using DUTCH Cycle Mapping Plus).
Cycling patients
Mid-luteal phase – which may be: 5-7 days after ovulation (consider confirming this with LH strips), 7 days before the expected period.
Menopausal patients
Collect any day
Irregular cycles
See ‘Is my patient ovulating?’
Male patients
Collect any day
Patients with regular cycles (approximately 28 days) will ovulate regularly, usually on day 14. Often there can be signs of ovulation, such as increased basal body temperature and cervical mucus changes, however the recommended way to determine ovulation for the DUTCH test is to confirm a rise in LH using LH detection strips or an ovulation prediction kit.
Patients with longer or shorter cycles may ovulate at a different time. See when to collect.
Detecting ovulation can be difficult in some patients (such as during perimenopause) as some can ovulate without a bleed, and some can bleed without ovulating (anovulatory cycles). These situations are also common with the use of the Mirena IUD (see below). Others can ovulate without showing overt signs.
Due to these common difficulties, Precision Analytical recommend using ovulation prediction kits to detect whether ovulation is likely occurring, and when.
Patients with longer or shorter cycles may ovulate at a different time. See when to collect.
Detecting ovulation can be difficult in some patients (such as during perimenopause) as some can ovulate without a bleed, and some can bleed without ovulating (anovulatory cycles). These situations are also common with the use of the Mirena IUD (see below). Others can ovulate without showing overt signs.
Due to these common difficulties, Precision Analytical recommend using ovulation prediction kits to detect whether ovulation is likely occurring, and when.
The recommended way to determine ovulation for the DUTCH test is to confirm a rise in LH using LH detection strips or an ovulation prediction kit (OPK). These are available online, from pharmacies and supermarkets.
How to use LH strips / OPK
Use a LH strip every morning until a positive result. Once there is a positive result, it means the patient is likely to ovulate very soon. Stop using the kit and wait 5-7 days to collect the DUTCH test.
If no ovulation/positive OPK occurs the first month and the patient does not get their period, try again for a second month. If no ovulation or period occurs after 60 days, consider testing on any day but be aware that the estrogen and progesterone levels will likely be below the luteal ranges. If the patient suddenly has their period, stop the OPK kit. Count forward from day 1 of bleeding and collect on days 19, 20 or 21.
In irregular cycles also consider completing the DUTCH Cycle Mapping test.
If the patient collects the DUTCH test and unexpectedly starts their period within 3 days of collecting, they will need to recollect. Dispose of the test and call RN Labs to organise a recollection.
If the patient collects and does not start their period within 10 days of collection, they will need to notify their practitioner to determine if a recollection is required. If so, contact RN Labs to disregard the collection, and organise a recollection kit.
Progestin Only
Precision Analytical do not recommend testing DUTCH Complete or DUTCH Plus while using progestin only medication as the sex hormone results are of diminished value. However, the DUTCH Adrenal and DUTCH CAR can still provide valuable insights.
Progestin-only contraception including the Mini Pill and Implanon often suppress ovulation and progesterone. Some patients still ovulate using these methods. The DUTCH test does not measure the synthetic progestin in these OCPs and implants.
Combined Progestin & Ethinyl Estradiol
Precision Analytical do not recommend testing DUTCH Complete or DUTCH Plus while using these medications as the sex hormone results are of diminished value. However, the DUTCH Adrenal and DUTCH CAR can still provide valuable insights.
The oral contraceptive pill (OCP) suppresses estrogen and progesterone production. Vaginal rings, birth control patches and injections all have similar effects.
Stopping the OCP on day 19-22 will not induce ovulation and will likely bring on an early menstrual cycle or increase risk of pregnancy. Testing during the sugar pill week (withdrawal period) will also result in predictably low estrogen and progesterone results.
Hormonal IUD
Progestin-containing intrauterine devices (e.g., Mirena) sometimes suppress ovulation and progesterone, however some patients still ovulate and cycle regularly with a hormonal IUD. For this reason, Precision Analytical recommend using an ovulation prediction kit to determine if the patient is ovulating (see when to collect).
The Mirena IUD may not always suppress estrogen as seen with OCP use, however, if the patient is not ovulating, sex hormones are likely to fall below the luteal range, diminishing the value of these results. The sex hormone metabolites can still provide valuable insight, as well as androgens, adrenals and organic acids.
Precision Analytical do not recommend testing DUTCH Complete or DUTCH Plus while using progestin only medication as the sex hormone results are of diminished value. However, the DUTCH Adrenal and DUTCH CAR can still provide valuable insights.
Progestin-only contraception including the Mini Pill and Implanon often suppress ovulation and progesterone. Some patients still ovulate using these methods. The DUTCH test does not measure the synthetic progestin in these OCPs and implants.
Combined Progestin & Ethinyl Estradiol
Precision Analytical do not recommend testing DUTCH Complete or DUTCH Plus while using these medications as the sex hormone results are of diminished value. However, the DUTCH Adrenal and DUTCH CAR can still provide valuable insights.
The oral contraceptive pill (OCP) suppresses estrogen and progesterone production. Vaginal rings, birth control patches and injections all have similar effects.
Stopping the OCP on day 19-22 will not induce ovulation and will likely bring on an early menstrual cycle or increase risk of pregnancy. Testing during the sugar pill week (withdrawal period) will also result in predictably low estrogen and progesterone results.
Hormonal IUD
Progestin-containing intrauterine devices (e.g., Mirena) sometimes suppress ovulation and progesterone, however some patients still ovulate and cycle regularly with a hormonal IUD. For this reason, Precision Analytical recommend using an ovulation prediction kit to determine if the patient is ovulating (see when to collect).
The Mirena IUD may not always suppress estrogen as seen with OCP use, however, if the patient is not ovulating, sex hormones are likely to fall below the luteal range, diminishing the value of these results. The sex hormone metabolites can still provide valuable insight, as well as androgens, adrenals and organic acids.
The DUTCH test is commonly used to assess sex hormones, adrenal function and organic acids during use of HRT.
Practitioners should consider what insights they are seeking through DUTCH testing and decide if they want to assess function and sex hormone metabolites while patients are taking HRT (most common), or if they want to assess baseline function without the use of HRT (contact Tech Support).
There are specific instructions for when to test around various forms of HRT. Please review the test collection instructions regarding hormone use.
For further clarification, please contact Tech Support.
Practitioners should consider what insights they are seeking through DUTCH testing and decide if they want to assess function and sex hormone metabolites while patients are taking HRT (most common), or if they want to assess baseline function without the use of HRT (contact Tech Support).
There are specific instructions for when to test around various forms of HRT. Please review the test collection instructions regarding hormone use.
For further clarification, please contact Tech Support.
This test is not intended to monitor HRT medications however it can be used to gain insight into sex hormone metabolites, adrenal function and organic acids. The DUTCH test measures bio-identical hormones but does not detect synthetic hormones.
It is important to understand what form of HRT your patient is using to determine how the results will be affected. For further clarification, please contact Tech Support.
It is important to understand what form of HRT your patient is using to determine how the results will be affected. For further clarification, please contact Tech Support.
The reference ranges are calculated based on testing “healthy” folks. Estradiol, for example is based on over 1,000 measurements with patients pre-screened to be off of birth control and other hormones. Precision Analytical only use the data for estradiol if the progesterone is within the luteal range. The postmenopausal ranges are based on women’s samples that are >55 years old with progesterone levels that are NOT in the luteal range. These women are also pre-screened to make sure they are not on hormones. Precision Analytical also offer follicular and ovulatory ranges for some hormones. These are based on fewer measurements of cycling women.
For estradiol, Precision Analytical use a 20th-80th percentile range. For progesterone, they use a 20th-90th percentile range (since modestly elevated progesterone is not as likely to be associated with issues compared to estrogen). That type of approach is used and a case-by-case approach is used for each hormone. For example, our range for 4-OH-E1 begins with zero (range = 0-80th percentile), not an actual value. We don’t want to tell anyone they are deficient for a carcinogenic estrogen! Precision Analytical also have age-dependent ranges for DHEA and testosterone (men only for T). The ranges are based on extensive testing. Precision Analytical’s actual reports show a woman’s reproductive hormones relative to both pre and postmenopausal ranges, which can be very helpful if you’re using HRT. The results shown here, for example, are from a postmenopausal woman who is obese. Her progesterone is where it belongs, but her estrogens are way high (up and into the premenopausal range) because she is inflamed and obese.
The DUTCH test performs at a high level (reproducible and accurate) but Precision Analytical are engaged in an endless pursuit of improved performance and some of these improvements require slight adjustments to reference ranges.
A combination of Pantothenic B5, Magnesium Citrate and Ascorbic Acid would be ideal for supporting cortisol production.
Test Pricing
To authorise this test for a patient, please visit the Practitioner Hub.
References
- Adam EK, Doane LD, Zinbarg RE, Mineka S, Craske MG, Griffith JW. Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence. Psychoneuroendocrinology. 2010 Jul;35(6):921-31.
- Chida Y, Steptoe A. Cortisol awakening response and psychosocial factors: a systematic review and meta-analysis. Biol Psychol. 2009 Mar;80(3):265-78 3. Clow A, Hucklebridge F, Stalder T, Evans P, Thorn L. The cortisol awakening response: more than a measure of HPA axis function. Neurosci Biobehav Rev. 2010 Sep;35(1):97-103. 4. Fries E, Dettenborn L, Kirschbaum C. The cortisol awaking response (CAR): Facts and future directions. International Journal of Psychophysiology 2009 Apr, 72(1):67-73 5. Huber TJ, Issa K, Schik G, Wolf OT. The cortisol awakening response is blunted in psychotherapy inpatients suffering from depression. Psychoneuroendocrinology. 2006 Aug;31(7):900-4 6. Jakuszkowiak-Wojten K, Landowski J, Wiglusz MS, Cuba?a WJ. Cortisol awakening response in drug-naïve panic disorder. Neuropsychiatr Dis Treat. 2016 Jun 27;12:1581-5 7. Roberts AD, Wessely S, Chalder T, Papadopoulos A, Cleare AJ. Salivary cortisol response to awakening in chronic fatigue syndrome. Br J Psychiatry. 2004 Feb;184:136-41.
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