The DUTCH Plus test by Precision Analytical provides in-depth hormone testing and offers clinicians and patients additional insight into an individual’s hormone balance and hormone metabolism.
DUTCH stands for "Dried Urine Test for Comprehensive Hormones," offering a comprehensive assessment of hormone levels and their metabolites. Unlike other hormone testing methods, the DUTCH Plus test utilizes dried urine samples collected over a 24-hour period, providing a more accurate and comprehensive snapshot of hormone production and metabolism throughout the day.
This innovative approach allows for the evaluation of not only steroid hormones like cortisol, testosterone, and estrogen but also their metabolites, offering deeper insights into hormone metabolism and potential imbalances.
The inclusion of salivary testing in the DUTCH Plus test provides a complementary perspective on adrenal hormone levels, offering insights into the free, biologically active fraction of cortisol throughout a 24 hour period. Salivary testing assesses hormone levels at specific times throughout the day, enhancing the understanding of diurnal hormone rhythms and facilitating a more comprehensive evaluation of hormone balance and function.
Also included as part of the DUTCH Plus test is a cortisol awakening response (CAR), which provides deeper insight into an individual’s HPA (hypothalamic-pituitary-adrenal) balance and current state of resilience against stress.
In addition to testing for adrenal and sex hormones, the DUTCH Plus also includes the DUTCH Organic Acids Test (DUTCH OATs). By analyzing a unique combination of neurotransmitter metabolites, nutritional organic acids, oxidative stress markers, and melatonin levels through urine samples, the DUTCH OATs test offers valuable insights into various health aspects including nutritional deficiencies, hormone and neurotransmitter imbalances, and oxidative stress.
The DUTCH Plus test offers a holistic view of hormone function, encompassing adrenal and sex hormones, as well as their metabolites, plus organic acids in a single test. This comprehensive assessment enables healthcare providers to identify hormonal imbalances, adrenal dysfunction, estrogen metabolism issues, and other factors that may underlie fatigue, mood swings, weight gain, and reproductive health issues.
The DUTCH Plus test empowers practitioners to develop targeted treatment plans tailored to each patient's unique hormone profile, facilitating personalized interventions aimed at restoring hormonal balance and optimizing overall health and well-being.
This test cannot be ordered for patients under 12 years of age.
Progesterone Metabolites
Estrogens and Metabolites
Androgens and Metabolites
Creatinine
Cortisol Metabolites and DHEA-S
Nutritional Organic Acids
Neuro-related Markers
Additional Markers
Free Cortisol and Cortisone (Saliva)
Salivary measures are taken 5 times in a 24 hour period to describe the individual’s diurnal cortisol and cortisone patterns, as well as her or his cortisol awakening response (CAR). It also includes measurements of total salivary cortisol and cortisone.
An additional salivary cortisol and cortisone reading is available for people who wake in the middle of the night and have difficulty returning to sleep.
The three main active estrogens in the human body are estrone or E1; estradiol or E2; and estriol, or E3. The DUTCH Plus test measures levels of these 3 primary estrogens in the urine, as well as some important metabolites.
Estrogen is essential for maintaining reproductive function and overall hormonal balance. Both estrogen excess and estrogen deficiency can both cause clinical symptoms and increase the risk of certain chronic illnesses.
Excess estrogen can cause a clinical picture of estrogen dominance, with symptoms including fibrocystic, tender breasts and/or breast cysts; heavy menstrual bleeding, and menstrual cycle irregularity; headaches; mood swings; weight gain; and fibroids. Long-term elevated estrogen levels increase a person’s risk of gallbladder and thyroid disease, estrogen receptor-positive cancers, endometriosis, blood clots and stroke. [4.]
In contrast, estrogen deficiency causes a clinical picture typically seen in menopause: hot flashes, night sweats, insomnia, heart palpitations, loss of libido, vaginal dryness, rapidly aging skin, mood swings and irritability, and others. A woman with chronically low estrogen levels may be at increased risk for osteoporosis, cardiovascular disease, early cognitive decline, and sexual and urogenital concerns. [32.]
Estradiol: Estradiol has the strongest action at estrogen receptors, making it the primary estrogen hormone responsible for regulating the menstrual cycle, reproductive health, and bone density in women.
Estrone and Estriol: These hormone levels typically rise above normal levels in the body with hormone supplementation, with few exceptions: estrone levels may rise normally in menopause.
Estriol levels rise normally in pregnancy.
Phase 1 Estrogen Metabolites: these are 2-OH estrone, 16-alpha-OH estrone, and 4-OH estrone. These are still active at estrogen receptors, so it is possible for parent estrogen levels and progesterone levels to be within range, but still have a functional estrogen dominance if these metabolites are elevated.
2-OH estrone is primarily metabolized through the CYP1A1 pathway, potentially exerting protective effects. 4-OH estrone is metabolized via the CYP1B1 pathway, potentially associated with increased estrogenic activity, more DNA damage and oxidative stress. 16-alpha OH-estrone is metabolized through the CYP3A4 pathway, which is considered proliferative: good for supporting bone health, but dangerous in the setting of estrogen receptor-positive cancers. [23.]
Phase 2 Estrogen Metabolites: this is demonstrated through 2-methoxy estrone, which is also an indicator of methylation activity. Slowed methylation activity in the liver can cause phase 1 estrogen metabolites to build up, potentially leading to estrogen dominance and the proliferation of estrogenic cancer cells.
Progesterone: Progesterone plays a crucial role in regulating the menstrual cycle, supporting pregnancy, and maintaining hormonal balance. It helps prepare the uterus for implantation of a fertilized egg and is essential for maintaining pregnancy.
High progesterone levels are most often seen with progesterone supplementation. Through complex negative feedback loops, progesterone excess symptoms often mimic an estrogen dominance presentation. [2.]
Low progesterone levels are more common in the clinical setting and may be related to infertility and/or recurrent miscarriages and sleep problems. In addition, symptoms of estrogen excess are common in the setting of progesterone deficiency. [2.]
Progesterone levels are also affected by HPA axis function; chronic stress can alter progesterone availability, highlighting the intricate relationship between healthy stress levels and healthy hormones. [3.]
It is important to note that progesterone levels are not detected in urine hormone testing. Instead, progesterone’s two main metabolites are measured: alpha-pregnanediol and beta-pregnanediol. Research shows that the sum of these two metabolites correlates well with serum progesterone (although not with orally or sublingually supplemented progesterone). [20., 21.]
Alpha-pregnanediol has actions at the GABA receptor in the central nervous system, which correlates with positive effects on mood and sleep. In contrast, beta-pregnanediol, the main progesterone metabolite, does not.
Testosterone: Testosterone contributes to libido, muscle mass, bone density, and overall sense of well-being. Low testosterone levels in women can lead to symptoms such as low libido, fatigue, and mood disturbances.
In contrast, high testosterone levels are associated with androgenic hair loss, acne, depression, insulin resistance and PCOS, or polycystic ovarian syndrome, and infertility in women. [27., 28., 31., 36.]
Testosterone Metabolites: The DUTCH Plus tests for urinary testosterone, or bioavailable testosterone. This can also be understood by looking at its metabolites: 5 alpha-dihydrotestosterone (5a-DHT), the most potent form of testosterone; 5 alpha-androstanediol, the metabolite of 5a-DHT, which may better reflect tissue activity of 5a-DHT; and 5 beta-androstanediol.
5 beta-androstanediol is not as active as 5a-DHT or 5 alpha-androstanediol at the tissues, so it is not correlated with androgenic symptoms such as acne, hair loss, libido, and others.
DHEA-S and Metabolites: DHEA is a prohormone made in the adrenal glands and sulfated to DHEA-S peripherally, which is often measured in the serum. The best correlation to total DHEA production from the adrenal glands appears to be the sum of DHEA-S and its two metabolites, etiocholanolone, and androsterone. [26.]
Knowing a person’s DHEA level is an important indicator of adrenal function; additionally, because DHEA can be converted to testosterone and then to estrogen, DHEA has many known health benefits: bone health, sexual health and fertility, brain health, immune and cardiovascular health. [26.]
Cortisol is widely recognized as the body's primary stress hormone, playing a key role in the "fight or flight" response. It facilitates various bodily functions to respond to stress by increasing blood sugar levels, enhancing the brain's use of glucose, and limiting nonessential or harmful processes in a crisis, such as the immune response, digestion, and reproduction.
Cortisol's production follows a diurnal rhythm, with levels peaking in the early morning and gradually tapering off throughout the day, reaching their lowest at night. This pattern helps regulate various bodily functions, including sleep-wake cycles and energy management.
Because of its many roles in physiological functions including the stress response, metabolism, digestion, circadian rhythms and immune regulation, chronically elevated levels of cortisol may have many implications on human health. [24.]
Cortisol is locally deactivated to cortisone at the salivary glands and kidneys. Knowing the cortisone levels in saliva or urine is necessary for a complete understanding of adrenal function; for example, if the diurnal cortisol curve is low but the cortisone curve is elevated, this demonstrates increased activity of the enzyme 11b-HSD2 that deactivates cortisol to cortisone. When only the diurnal cortisol curve is available, the total amount of adrenal cortisol produced is not known. [22.]
DHEA-S is the sulfated form of the prohormone DHEA. Unlike cortisol, DHEA-S levels do not fluctuate significantly throughout the day, making them a reliable marker for long-term adrenal function.
In healthy individuals, cortisol is expected to rise in the morning by as much as 50%, peak approximately 30 minutes after waking, and fall back to morning waking levels within 60 minutes of waking [5.] . This is called the Cortisol Awakening Response, or CAR. [29.]
The Cortisol Awakening Response (CAR) is clinically relevant because it reflects HPA axis function, which is associated with various physiological and psychological factors. Research suggests that a robust CAR is indicative of healthy stress regulation and adaptation, while blunted or exaggerated CARs are linked to conditions such as chronic stress, PTSD, depression, chronic fatigue, and burnout. [10., 17., 30., 34., 35.]
Assessing CAR through laboratory testing such as the DUTCH Plus by Precision Analytical can aid in identifying dysregulations in the hypothalamic-pituitary-adrenal (HPA) axis, which plays a central role in the body's stress response system.
The DUTCH Plus test includes organic acids testing for the following biomarkers:
Two neurotransmitter metabolites: HVA (Homovanillic Acid) and VMA (Vanillylmandelic Acid)
Four nutritional organic acids: Kynurenic Acid, Quinolinic Acid, 3-Hydroxyisovaleric Acid, MMA (Methylmalonic Acid)
Additional markers for health assessment: Xanthurenic Acid, Pyroglutamic Acid, Indican (a marker of gut dysbiosis), 8-OHdG (a marker of oxidative stress), and Melatonin (a hormone related to sleep and circadian rhythm).
In addition to providing valuable information about a patient’s current metabolic status, this information also has clinical relevance regarding optimal hormone function and balance.
For example, HVA and VMA are also markers for enzymes that function in hormone processing, such as COMT. Imbalances here could also drive functional hormone imbalance.
The organic acids selected are also markers that can assess for the nutrient status of particular B vitamins which may also have effects on hormones. [8., 14.]
Dysbiosis has been associated with alterations in estrogen circulation. [1.] Increased oxidative stress may indicate a need to reduce inflammation and a deeper dive into estrogen processing. [LIRA]
There may be times where one form of hormone testing is recommended over others. [5., 7., 12., 16., 19., 20., 21.]
Urinary testing involves measuring hormone metabolites excreted in urine to provide a comprehensive assessment of hormone metabolism over a period of time, often 24 hours. This non-invasive test is suitable for assessing metabolism and detoxification of hormones, and is an indirect marker of hormone levels in the body.
Urinary testing offers insights into a person’s likelihood of developing certain hormone-related conditions by assessing hormone metabolites, such as the 2:16α-hydroxyestrone ratio and assessment of phase 1 and phase 2 detoxification pathways which have implications for breast cancer risk.
Testosterone metabolites can also be assessed, which have been implicated in the pathogenesis of conditions including breast cancer and polycystic ovary syndrome (PCOS). [5., 19.]
Urinary hormone levels may be influenced by factors such as hydration status and kidney function, and results may not always reflect serum hormone levels accurately.
Studies demonstrate that urine testing may be an appropriate method to monitor hormone replacement therapy for certain hormones, particularly estrogen. [20., 21.] However, urine testing may not reflect real-time hormone levels available to tissues as well as saliva or blood tests.
Blood testing measures hormone levels in serum, providing a snapshot of total hormone concentrations at a specific point in time. It is widely used in clinical practice due to its convenience and reliability. Blood testing is useful for assessing serum levels of sex hormones, including estrogen, progesterone, and testosterone, and is commonly used for diagnosing hormone-related conditions such as hypogonadism, PCOS and menopause. However, blood testing may not capture fluctuations in hormone levels throughout the day and may be influenced by factors such as stress or medication use.
Single-point hormone measurements in blood may not capture diurnal variations in hormone levels. And certain hormones, particularly cortisol, may be affected by the stress of blood collection, leading to potential inaccuracies.
Saliva testing measures the unbound, biologically active fraction of hormones present in saliva, providing insights into hormone levels that are readily available to target tissues. Saliva testing is non-invasive and can be performed easily at home, making it convenient for patients. It is particularly useful for assessing free, bioavailable hormone levels, which may better reflect tissue-level hormone activity compared to serum levels. [12.] However, saliva testing may not accurately reflect total hormone levels, and interpretation may vary depending on the assay used.
The DUTCH Plus Test by Precision Analytical is beneficial for individuals seeking a comprehensive assessment of sex hormone metabolism and oxidative stress levels. Specifically, it is suitable for:
Individuals with hormone-related conditions: Those experiencing symptoms related to hormonal imbalances, such as irregular menstrual cycles, infertility, mood swings, or symptoms of androgen excess or deficiency, may benefit from this test. Conditions such as polycystic ovary syndrome (PCOS), menopause-related symptoms, and hormone-sensitive cancers may also warrant testing. [5., 6., 15., 19.]
Individuals undergoing hormone therapy: Individuals undergoing hormone replacement therapy, particularly estrogen replacement, can benefit from monitoring their hormone metabolites to assess treatment effectiveness and ensure hormonal balance. [20., 21.]
Individuals interested in preventive health: As hormonal imbalances and oxidative stress are associated with various health conditions including cancer, cardiovascular disease, and neurodegenerative disorders, people interested in preventive health and optimizing their overall well-being may benefit from this test to identify potential risk factors and guide preventive strategies. [9., 11., 13., 25.]
Those seeking personalized health management: Individuals interested in personalized health management and optimizing their hormone balance may benefit from this test to gain insights into their sex hormone metabolism and oxidative stress levels, allowing their practitioner to tailor interventions and lifestyle modifications to their unique needs to promote overall health and well-being.
Individuals struggling to lose weight: hormonal imbalances and oxidative stress can contribute to weight loss challenges. Research suggests that hormonal imbalances, including abnormalities in estrogen, progesterone, and testosterone levels, can impact metabolism, appetite regulation, and energy expenditure, potentially hindering weight loss efforts. [6., 33.] Oxidative stress has been implicated in obesity and metabolic dysfunction, leading to insulin resistance and inflammation, which can further exacerbate weight management difficulties. [9., 11.] By assessing sex hormone metabolites, adrenal hormones, and certain organic acids levels, the DUTCH Plus can provide insights into hormonal imbalances and stress levels that may be contributing to weight management challenges.
Overall, the DUTCH Plus is suitable for individuals seeking a comprehensive assessment of their hormone metabolism and oxidative stress levels, helping to guide personalized treatment strategies and optimize health outcomes.
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The DUTCH Plus™ offers an extensive assessment of sex and adrenal hormones and their metabolites. It also assesses the Cortisol Awakening Response (CAR) and includes the insomnia cortisol sample. This test cannot be ordered for patients under 12 years of age.
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In this class, you'll gain insight into how gut health and immune balance may be connected, the role of key markers like Zonulin and oxidative stress indicators, and strategies to help support gut barrier integrity and immune resilience.
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