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Metabolized cortisol tells you something that no single salivary or blood cortisol reading can: how much total cortisol your adrenal glands actually produced over a full day. Free cortisol in saliva or blood is a snapshot, capturing what is circulating at one moment. Metabolized cortisol is the bigger picture. It is the sum of cortisol's three main permanent breakdown products in urine: a-THF (alpha-tetrahydrocortisol), b-THF (beta-tetrahydrocortisol), and b-THE (beta-tetrahydrocortisone). Once cortisol has been converted into these metabolites, they cannot be reactivated. They are simply excreted. Adding them up gives you an estimate of everything your adrenals produced and your body processed for the day.
This is why metabolized cortisol may be the best marker for assessing total adrenal cortisol production. The salivary or urinary free cortisol readings only capture about 5% of total circulating cortisol; the other 95% is bound to carrier proteins in the blood and does not appear in saliva. Metabolized cortisol captures the full throughput, including cortisol that was bound, released, used, deactivated to cortisone, and then permanently broken down.
One of the most clinically important things about metabolized cortisol is that it does not always match your free cortisol readings. This discrepancy is explained by the cortisol clearance rate (CCR). If your body clears cortisol quickly (a fast CCR), your free cortisol may look low while your metabolized cortisol is above range. This is because cortisol is being broken down and excreted rapidly, leaving less in circulation at any given moment even though total production is high.
The reverse also applies. If your clearance rate is slow, free cortisol may appear elevated while metabolized cortisol is normal or low, because cortisol is lingering in the bloodstream longer rather than being processed. When you see a mismatch between free cortisol (from saliva) and metabolized cortisol (from urine), the clearance rate is usually the explanation. Always interpret the two together.
Your thyroid function, body composition, and insulin status all influence the enzymes that break down cortisol (5a-reductase, 5b-reductase, and 3a-HSD). Because of this, metabolized cortisol reflects both adrenal output and metabolic clearance speed. A full thyroid panel is a reasonable companion test if metabolized cortisol is unexpectedly high or low.
| Result | What It May Reflect | Clinical Associations |
|---|---|---|
| Low | Total adrenal cortisol production may be low | Long-term stress, poor sleep hygiene, untreated chronic sleep apnea, pituitary or hypothalamic dysfunction, medications that suppress HPA axis activity (glucocorticoids, opioids, NSAIDs, tricyclic antidepressants). Less common: traumatic brain injury, congenital adrenal hyperplasia, Addison's disease (metabolized cortisol typically below 1,000 ng/mg) |
| High | Total adrenal cortisol production may be high | Stress, anxiety, acute inflammation, infection, pain, caffeine, blood sugar dysregulation, Cushing's syndrome, oral hydrocortisone supplementation |
| Within range | Total cortisol production appears appropriate for the clinical situation | Does not rule out conditions that could result in low or high metabolized cortisol; always assess alongside free cortisol and the cortisol clearance rate |
What this means for you: a within-range metabolized cortisol is reassuring but not definitive. If your free cortisol is elevated and your metabolized cortisol is normal or low, it suggests your clearance rate is slow. If your free cortisol is low but metabolized cortisol is above range, your adrenals may be producing plenty of cortisol, but it is being cleared so rapidly that circulating levels stay low. The relationship between these two numbers is where the clinical insight lives.
Metabolized cortisol can also be compared with your total DHEA production to assess whether your body is in a more catabolic (tissue-breaking) or anabolic (tissue-building) state. When cortisol is relatively higher than DHEA, the body may be in a catabolic state, which can result in the breakdown of body tissues, weakness, impaired tissue repair, and altered immune function. When DHEA is relatively higher than cortisol, the body may be in an anabolic state, which can promote gains in muscle mass from exercise and support tissue repair. If both are elevated or both are low, neither picture dominates.
When metabolized cortisol is high but free cortisol and cortisone are low, cortisol levels may differ depending on location within the body. Cortisol may be elevated in the adrenal glands, potentially driving increased conversion of noradrenaline to adrenaline. At the same time, cortisol may be low in the brain, which could trigger increased ACTH secretion from the pituitary. In this scenario, efforts aimed at increasing overall HPA axis activity should be approached with caution, as they may worsen some symptoms.
Metabolized cortisol is shaped by two forces: how much cortisol the adrenals produce, and how quickly the body's enzymes break it down. Interventions can target either side.
Factors that increase cortisol metabolism: Obesity, high insulin levels, and hyperthyroidism (or excessive thyroid medication) all speed up the enzymes that break cortisol down, increasing metabolized cortisol. Inflammation and long-term stress may also elevate metabolized cortisol by driving higher adrenal output. In obesity specifically, fat tissue sequesters cortisol, which may in turn stimulate the adrenals to produce more.
Factors that slow cortisol metabolism: Hypothyroidism (or insufficient thyroid medication), very low calorie intake (anorexia), low bile acid levels (cholestasis), and poor liver and mitochondrial function all slow the breakdown enzymes, which may lower metabolized cortisol even if adrenal output is adequate.
For low metabolized cortisol: Address underlying causes such as chronic stress, poor sleep, or medication-induced HPA suppression. Foundational HPA axis support may include B vitamins, vitamin C, adaptogenic herbs (ashwagandha, rhodiola, Korean ginseng, cordyceps, schizandra, bacopa, licorice root), blood sugar regulation, and sleep hygiene. Licorice root limits the deactivation of cortisol into cortisone, potentially raising active cortisol, but must be used with caution in those with high blood pressure.
For high metabolized cortisol: Calming herbs (ashwagandha, skullcap, holy basil, cordyceps, jujube, mimosa, chamomile, lemon balm, passionflower, valerian, magnolia, California poppy), parasympathetic nervous system support (meditation, breath work, vagal nerve stimulation), GABA support (GABA, L-theanine, honokiol), blood sugar regulation, anti-inflammatory strategies (turmeric, resveratrol, fish oil, EGCG), and stress reduction may help bring production and clearance back toward balance.
5a-reductase inhibitors such as finasteride and dutasteride inhibit one of the enzymes responsible for producing a-THF. These medications may lower the alpha metabolite portion of metabolized cortisol. If you are taking one, note this when interpreting your result.