Hormones are critical messengers that regulate just about every function in the body, from growth and development to metabolism and reproduction. Hormone imbalances can cause weight gain, fatigue, mood swings, and infertility, to name just a few.
Nutritional endocrinology is the study of the impact of nutrition and lifestyle on hormonal function. One of the critical components is a variety of types of testing for hormone balance.
Among the most important tests for hormone balance are those that test not just the free and bound hormones, but the hormone metabolites as well. Metabolite testing is a valuable tool that can help identify hormonal imbalances and provide insight into the root causes of many health problems.
What is hormone metabolite testing?
Hormone metabolite testing is a non-invasive, comprehensive evaluation of the breakdown products, or metabolites, of hormones, most commonly in urine samples. Hormones are metabolized by the liver and excreted through urine, so hormone metabolite testing can provide a more accurate and complete picture of hormone levels than traditional hormone tests.
Why is hormone metabolite testing important?
Hormone metabolite testing can provide valuable information about hormone production, metabolism, and elimination in the body. It can help identify imbalances in hormone levels that may be causing health problems, such as fatigue, weight gain, insomnia, and mood swings.
Hormone metabolite testing can also help identify the root causes of hormonal imbalances, such as nutrient deficiencies, stress, environmental toxins, and genetic factors.
Hormone metabolite testing can also be used to determine whether hormone replacement therapy is safe, to monitor doses and evaluate its effectiveness.
HRT is often prescribed to alleviate menopausal symptoms, such as hot flashes, vaginal dryness, and mood swings. However, HRT can also increase the risk of breast cancer, heart disease, and stroke. Hormone metabolite testing can help determine the optimal dosage and type of hormone therapy for each individual, minimizing the risks and maximizing the benefits.
Who can benefit from hormone metabolite testing?
Anyone experiencing symptoms related to hormonal imbalances, such as fatigue, weight gain, mood swings, and insomnia, can benefit from hormone metabolite testing.
The most commonly measured metabolites are cortisol and cortisone, estrogen and testosterone.
Female hormone metabolite testing is particularly useful for women experiencing menopausal symptoms, as well as women with irregular menstrual cycles, fertility problems, and polycystic ovary syndrome (PCOS).
Hormone metabolite testing is also recommended for men experiencing symptoms of low testosterone, such as decreased libido, erectile dysfunction, and muscle loss. Metabolite testing can evaluate whether a man is a good candidate for testosterone replacement or whether there is a risk of excess estrogen or DHT, a highly potent and potentially dangerous metabolite of testosterone.
Plus, people with a family history of hormone-related cancers, such as breast, ovarian, or prostate cancer, can benefit from hormone metabolite testing to assess their risk.
What Tests are Used to Measure Hormone Metabolites
The DUTCH is a type of steroid hormone test that has gained popularity in recent years. It is a comprehensive urine test that measures hormone metabolites produced by the adrenal glands and sex hormones produced by the ovaries and testes.
The DUTCH uses dried urine to measure the levels of various hormones and metabolites. The test is unique in that it measures both the free and metabolized forms of hormones, giving a more comprehensive picture of hormone levels in the body. The test is able to measure the levels of cortisol and cortisol metabolites, providing valuable information about adrenal gland function.
The DUTCH Test measures a variety of hormone metabolites, including:
- Cortisol metabolites – The test measures the levels of cortisol and cortisol metabolites, providing information about adrenal gland function and stress levels.
- Sex hormone metabolites – The test measures the levels of sex hormone metabolites, including estrogen, progesterone, and testosterone, providing information about adrenal, ovarian and testicular function.
The DUTCH provides a comprehensive picture of hormone levels in the body, allowing for more targeted management of hormone imbalances. The test can also provide valuable information about adrenal gland function, which is important for managing stress and overall health.
Cortisol and Cortisone Metabolite Testing
Cortisol and cortisone are two important hormones produced by the adrenal glands that play a vital role in regulating the body's stress response. These hormones are produced in response to stress and help the body cope with physical and emotional stressors. Measuring cortisol and cortisone metabolites can provide valuable information about adrenal gland function and overall health.
Cortisol is the primary stress hormone and helps regulate the body's response to stress, maintain blood sugar levels, and control blood pressure.
Cortisone is a less potent, less active form of cortisol that is produced by the adrenal glands and is converted to cortisol as needed by the body.
Cortisol and cortisone metabolites are the by-products of the metabolic breakdown of cortisol and cortisone in the body.
There are several cortisol and cortisone metabolites that can be measured, including:
- 11-beta-hydroxyandrostenedione (11-beta-OH-AD) – This metabolite is produced in the adrenal glands and is a precursor to cortisol and androgens.
- 11-beta-hydroxyetiocholanolone (11-beta-OH-ETIO) – This metabolite is produced in the adrenal glands and is a precursor to cortisol and androgens.
- Tetrahydrocortisone (THE) – This metabolite is produced from cortisol and is excreted in urine.
- Tetrahydrocortisol (THF) – This metabolite is produced from cortisol and is excreted in urine.
Why measure cortisol and cortisone metabolites?
Measuring cortisol and cortisone metabolites can provide valuable information about adrenal gland function, thyroid health, liver and kidney function, and overall health.
Cortisol Metabolites as an Indicator of Thyroid or Liver Dysfunction
Metabolites are downstream of the main hormone. All hormones have metabolites. They get broken down by the liver and eliminated either in the urine or the stool. When we look at the metabolites, it gives us so much more information than just looking at cortisol in the blood in the morning.
In functional medicine, we typically look at saliva as a good place to evaluate hormones, especially cortisol, because it allows us to see the pattern of hormone levels throughout the day. The downside of saliva testing is that you can't see the metabolites. You can only see the metabolites in the urine.
Measuring metabolites and comparing to total 24 hour cortisol production gives us information about more than just what's going on with adrenal function. It allows us to determine how well the person is eliminating the metabolites as well. This provides valuable information about potential liver and thyroid dysfunction.
Cortisone and Cortisol Ratios as a Marker of Adrenal, Liver and Kidney Function
The kidneys, salivary glands, and the colon deactivate cortisol to cortisone by an enzyme called 11?-HSD1. Why would we want to deactivate cortisol? To avoid large quantities of cortisol in circulation because it can raise blood pressure, blood sugar and so much more.
The body has a natural balance between cortisol and cortisone. When the cortisol levels are higher than needed, the body goes into protective mode and converts it into cortisone. This conversion occurs in the kidneys.
When more cortisol is needed, the liver and fat cells convert cortisone back into cortisol, via the enzyme 11?-HSD2.
The ratio of cortisol to cortisone is an effective way to evaluate adrenal function. The ratio of cortisol metabolites to cortisone metabolites allows us to evaluate the excretion of these hormones.
If the metabolites favor cortisol, it often indicates that there's a lot of reactivation of cortisone to cortisol, and it can be a sign of inflammation or taking licorice extract.
If the metabolites favor cortisone, it often indicates that the body's trying to protect itself from the high levels of cortisol, most especially from high blood pressure and high blood sugar.
These tests provide a fuller picture of what’s happening, and allows us to be better at identifying where the imbalances lie and what you need to do to support returning to a state of balance and good health.
Enzymes in the liver, 5?- or 5?-reductase are responsible for creating the metabolites, ?- tetrahydrocortisol, which is abbreviated ?-THF on the report, or ?-tetrahydrocortisol, ?-THF.
For cortisone, the main metabolite is tetrahydrocortisone or THE.
Cortisol Metabolite Testing Provides Valuable Information About Adrenal Function
What can you learn from the metabolites that you can't learn from just looking at the circadian rhythm of cortisol production?
In a situation where you look at the test and see that cortisol is super high, and metabolized cortisol is super high, it means that we have overactivity. We're in the alarm state where too much cortisol is being produced.
If we have low free cortisol along with low metabolites that means that the system is drained and is starting to lose the ability to make cortisol. If the metabolites are favoring cortisol, it’s an indication that the body is trying really hard to maintain cortisol levels at a reasonable level. It’s trying to hang on. If the metabolites favor cortisone, it means that the cortisol is being deactivated, usually to protect from the impact of high cortisol.
In the case of high free cortisol and low metabolites or high free cortisol with high cortisone can mean a number of things.
It can be because the metabolism is sluggish and the clearance is sluggish, that the body is not able to eliminate the excess cortisol, and so it's maintained in the system. This may be due to hypothyroidism, sluggish liver function, or anorexia.
What about low free cortisol when it accompanies high metabolized or even normal or high normal metabolized cortisol? Well, that means that the clearance is elevated. Often this occurs because someone is overweight, or obese and the extra fat is putting a strain on the system.
It could be hyperthyroidism, causing a situation where too much cortisol is being metabolized and eliminated, or the person is hypothyroid and is overmedicated, and it can show on the cortisol metabolite test even before it shows on the thyroid blood test. This might account for people who are being medicated and they're still tired. It could be because of this imbalance between the metabolites and the total cortisol.
It could also be due to chronic stress and HPA activation, or taking steroids. All this is to say that we need to look more deeply than noticing low cortisol on a saliva test and recommending adaptogens.
This is, in a nutshell, how to interpret DUTCH results and be able to understand the variety of combinations of results.
It’s impossible to describe all the variations that can occur. Each individual has a different set of biochemistry that's playing in and might be contributing to symptoms like fatigue, low libido, irritability, and anxiety, and this test can go a long way in helping you to understand it.
In reality, I find that you need to look at hundreds of these tests before you can interpret at a glance.
Minimize Risk of Estrogen Dominance by Testing Estrogen Metabolites
Just like cortisol metabolite testing is important to give a full picture of adrenal function, so too estrogen metabolism testing provides an important tool for truly understanding balance, risk factors and how and when to supplement with hormones.
Estrogen is classified into three categories, and there are metabolites related to each type
- Estrone (E1) – Estrone is the primary estrogen produced after menopause. It is converted from androstenedione, a hormone produced in the adrenal glands, and fat tissue.
- Estradiol (E2) – Estradiol is the most potent and prevalent estrogen produced before menopause. It is produced in the ovaries and plays a crucial role in the menstrual cycle, fertility, and bone health.
- Estriol (E3) – Estriol is a weaker estrogen that has a protective effect, vs estriol and estrone which can be proliferative, meaning that they can contribute to excess growth of estrogen sensitive tissue.
Effects of Estrogen Metabolites on the Body
Estrogen metabolites can have either beneficial or harmful effects on the body, depending on their type and quantity. The balance between estrogen metabolites is essential for overall health and wellbeing.
Beneficial Estrogen Metabolites
2-hydroxyestrone (2-OHE1) and 2-methoxyestrone (2-MeOHE1) are two of the most beneficial estrogen metabolites. They are produced through a specific metabolic pathway called the 2-hydroxylation pathway. These metabolites have several health benefits, including anti-inflammatory properties, antioxidant effects, and a decreased risk of breast cancer.
Harmful Estrogen Metabolites:
4-hydroxyestrone (4-OHE1) and 16 alpha-hydroxyestrone (16alpha-OHE1) are two of the most harmful estrogen metabolites.
4-hydroxyestrone (4-OHE1) has been found to be a cause of DNA damage and oxidative stress. 16-OH Estrone can also damage DNA but to a much lesser extent, and also has beneficial effects in that it can protect bone.
Both of these metabolites have several health risks, including an increased risk of breast cancer, oxidative damage to cells, and inflammation.
Estrogen Metabolite Testing
Estrogen metabolite testing can help determine the balance between beneficial and harmful estrogen metabolites in the body. The test results can provide valuable information about the risk of breast cancer and other health issues related to hormonal imbalances. The testing can also help guide treatment decisions, such as hormone replacement therapy, by optimizing the balance of estrogen metabolites in the body.
If you test metabolites and find that the ratio of the 4-OH metabolite is high, it may be prudent to work at lowering it before considering estrogen replacement therapy. 4-OH Estrone can be reduced by sulforaphane, found in broccoli sprouts and other brassica vegetables, and supplementation of DIM (D0-indole-methane) and I3C(Indole-3-carbonyl).
In conclusion, hormone metabolite testing is a valuable tool for assessing hormone levels and identifying hormonal imbalances. It can provide valuable insight into the root causes of health problems and help guide treatment decisions. If you are experiencing symptoms related to hormonal imbalances or are interested in optimizing your health and wellness, consider talking to your healthcare provider about hormone metabolite testing.
If you’ve done a DUTCH test, and are looking for help with interpretation, we can help. Sign-up for a DUTCH test Interpretation session with a certified Nutritional Endocrinology Practitioner.
Check out our Reinvent Healthcare Podcast Adrenal episodes to deep dive into adrenal testing and management. Our Nutritional Endocrinology Practitioner Certification provides a comprehensive approach to functional testing.