Quick answer: The cortisol-to-cortisone ratio compares active cortisol with its inactive form, cortisone, and reflects the work of the enzymes that switch cortisol on and off inside tissues. A higher ratio generally means less cortisol is being inactivated, so more of it stays active, while a lower ratio generally reflects more inactivation. Results depend on timing and test method, so they are best read alongside the daily cortisol pattern.
Key takeaways
The cortisol-to-cortisone ratio reflects enzymes that switch cortisol between its active and inactive forms.
Small studies show the ratio changes with body fat and after significant weight loss.
Evidence is limited, so it is read as one piece of a broader stress-hormone picture.
Have you ever wondered why two people with similar cortisol results can handle stress so differently? Part of the answer lies in what the body does with cortisol after it has been made. Cortisol is the active stress hormone, and cortisone is its inactive partner. Enzymes inside our tissues keep converting one into the other, so a urine test that measures both can hint at whether the body is leaning toward keeping cortisol active or switching it off. This article looks at that balance, which is a different question from the daily cortisol curve I cover in my other articles on stress hormones.
This article is educational. It explains what the marker reflects and how researchers connect it to the deeper mechanisms of aging, so you can have a more informed conversation with your own provider.
What does the balance between cortisol and cortisone tell you?
In a detailed review, Stewart and Krozowski described two enzymes, called 11-beta-hydroxysteroid dehydrogenase type 1 and type 2, that convert active cortisol into inactive cortisone and back again. The type 2 enzyme switches cortisol off, and in the kidney it protects the receptor that helps the body hold onto sodium from being overstimulated by cortisol. The type 1 enzyme works mostly in the other direction in tissues such as the liver and fat, turning cortisone back into active cortisol where it is needed.
Because urine collects the end result of this traffic, the ratio of cortisol to cortisone is often read as a rough window into how much cortisol the body is inactivating. A higher ratio generally reflects less conversion to cortisone, which means more cortisol stays active, while a lower ratio generally reflects more inactivation. A classic 1987 study in The Lancet by Stewart and colleagues gave liquorice to seven healthy volunteers and found a change in cortisol metabolism that pointed to a blocked type 2 enzyme, along with sodium retention. Results also differ with the time of collection and the test method, so they are best compared with the reference range of the specific test.
How is the cortisol and cortisone balance connected to aging and root causes?
This balance matters for aging because it controls how strongly each tissue hears the stress signal, regardless of how much cortisol the adrenal glands release. That makes it a clear example of changes in intercellular signaling, one of the core mechanisms researchers connect with aging. In their 2013 review in Physiological Reviews, Chapman, Holmes and Seckl explained that the type 1 enzyme is selectively raised in fat tissue in obesity, where it contributes to metabolic problems, and that it is also raised in the aging brain, where it adds to cortisol-related memory decline. In rodents, lowering this enzyme improved several metabolic measures and memory with age, although the authors noted that the benefit of blocking it in people remains unclear. This connects the topic to nutrient sensing and to how the body handles blood sugar and fat.
Skin offers another window. In a 2013 study in the Journal of Clinical Investigation, Tiganescu and colleagues found higher type 1 enzyme activity in skin samples from older people and in sun-exposed skin compared with protected skin from the same donors. In mice that lacked the enzyme, the thinning and disorganized collagen that normally comes with age did not develop, and cortisol at normal body levels slowed key steps in collagen production in skin cells. That ties local cortisol activation to proteostasis, the upkeep of the proteins that give tissues their structure.
It helps to be honest about what a urine ratio can and cannot show. It reflects the body as a whole, and the kidney’s type 2 enzyme has a large influence on it, so it cannot reveal what is happening inside one particular tissue. From a root-cause perspective, the questions I find most useful are about what shapes the balance. Ongoing stress, short or irregular sleep, training load and recovery, body fat around the middle, blood sugar regulation and liquorice intake are all worth considering. Kidney function, medications and genetics play a role too, since rare changes in the gene for the type 2 enzyme cause an inherited form of high blood pressure. Reading the ratio next to the daily cortisol pattern and DHEA usually gives a fuller picture.
What does the research show about Cortisol to Cortisone Ratio?
Researchers followed 31 women before and two years after weight-loss surgery and measured cortisol and cortisone breakdown products in urine. After weight loss, total cortisol metabolites fell and the cortisol-to-cortisone metabolite ratio decreased, consistent with less activity of the enzyme that turns cortisone back into cortisol in fat tissue. The study was small and involved surgical weight loss. (Rask et al., 2013)
In 21 adults with severe obesity studied before and after weight-loss surgery, total urinary cortisol metabolites fell from about 15,224 to 8,814 micrograms per day, and the cortisol-to-cortisone ratio in fat tissue dropped about three-fold. The sample was small, and changes after surgery may not match those from gradual weight change. (Woods et al., 2015)
These small studies show that the ratio reflects how tissues handle cortisol, especially in fat, but there is no large research base for using it as a routine test.
Related reading
If you would like to explore related topics, my articles on daily cortisol patterns, adrenal dysfunction and fasting insulin and HOMA-IR go deeper. You can also see the specialty tests I commonly recommend on my functional labs page.
Common questions about Cortisol to Cortisone Ratio
Is the cortisol-to-cortisone ratio the same as a cortisol test?
No. A cortisol test measures the active hormone, while the ratio compares it with its inactive form, which gives a sense of how much cortisol the body is switching off rather than how much it makes.
Why is liquorice mentioned with this ratio?
A small 1987 study in healthy volunteers found that eating liquorice changed cortisol metabolism in a way that pointed to a blocked enzyme for turning cortisol into cortisone, and this change came with sodium retention.
Can exercise training change the ratio?
A study of triathletes found that trained men converted more cortisol into cortisone overnight than untrained men, while two athletes who became overtrained showed a higher ratio.
Sources
This article is for educational purposes only and is not medical advice. It does not replace an individual evaluation. Talk with your healthcare provider before making changes to your diet, exercise, supplements, or medications, especially if you are pregnant, nursing, or managing a health condition.
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