What medication lowers cortisol levels? A guide to pharmaceutical options

October 11, 2025 •

4 min read

Chronic elevation of cortisol, a condition known as hypercortisolism, most notably affects patients with Cushing's syndrome, a disorder that impacts an estimated 1.5 million people in the United States. For these individuals, medication can play a vital role in normalizing hormone levels and managing the disease. Knowing what medication lowers cortisol levels is essential for effective treatment when other options, like surgery, are not suitable or have been unsuccessful.

Quick Summary

Chronic high cortisol, or hypercortisolism, is managed with various prescription drugs. Common treatments, particularly for Cushing's syndrome, include medications that inhibit cortisol production, block its effects on the body, or reduce the ACTH signal from the pituitary gland.

Key Points

Adrenal Enzyme Inhibitors: Block enzymes in the adrenal glands to prevent cortisol from being produced. Examples include osilodrostat and metyrapone.
Glucocorticoid Receptor Blockers: Prevent cortisol from binding to receptors in the body, blocking its effects on tissues rather than reducing its overall level. Mifepristone (Korlym) is a drug in this class.
ACTH Secretion Inhibitors: Reduce the production of adrenocorticotropic hormone (ACTH) by the pituitary gland, which in turn reduces cortisol production. Pasireotide (Signifor) works in this way.
Individualized Treatment Plans: The choice of medication is tailored to the specific cause of hypercortisolism (e.g., pituitary tumor vs. adrenal tumor) and the patient's health profile, including comorbidities like diabetes.
Risks and Side Effects: Cortisol-lowering medications carry significant risks, including hormonal imbalances, cardiovascular issues, and adrenal insufficiency, necessitating close medical supervision and frequent monitoring.
Medical Supervision is Essential: Never attempt to self-medicate or adjust the dose of cortisol-lowering medication without strict guidance from a qualified healthcare provider.

Understanding High Cortisol (Hypercortisolism)

Cortisol, often called the "stress hormone," is a vital glucocorticoid hormone produced by the adrenal glands. It plays a crucial role in regulating metabolism, immune function, and the body's response to stress. Hypercortisolism occurs when the body produces an excess of this hormone, which can lead to a range of severe health problems, including weight gain, high blood pressure, weakened bones, and mood disturbances.

The most common cause of sustained high cortisol is Cushing's syndrome. This condition can result from pituitary gland tumors that produce too much adrenocorticotropic hormone (ACTH), triggering overproduction of cortisol by the adrenal glands. Other causes include adrenal tumors or the long-term use of high-dose glucocorticoid medications. For patients whose hypercortisolism cannot be resolved through surgery or radiation, medication becomes a primary treatment option to regulate hormone levels.

Main Categories of Cortisol-Lowering Medication

Medications designed to lower cortisol work through different mechanisms, targeting specific points in the body's complex hormonal cascade. The three main classes are:

Adrenal Enzyme Inhibitors: These drugs block specific enzymes in the adrenal gland responsible for the final steps of cortisol synthesis.
Glucocorticoid Receptor Blockers: Instead of reducing cortisol production, these medications prevent the hormone from binding to its receptors, thereby blocking its effects on the body's tissues.
ACTH Secretion Inhibitors: These agents act on the pituitary gland to reduce the release of ACTH, which in turn lowers cortisol production by the adrenal glands.

Adrenal Enzyme Inhibitors

These medications are often a frontline defense for controlling cortisol production directly at the source, the adrenal glands.

Osilodrostat (Isturisa): An FDA-approved medication for Cushing's syndrome, osilodrostat works by inhibiting the enzyme 11-beta-hydroxylase, which is essential for cortisol biosynthesis. In clinical trials, this oral medication has been shown to effectively normalize cortisol levels in a significant number of patients.
Metyrapone (Metopirone): This potent, short-acting inhibitor blocks the final step in cortisol synthesis. It is effective for rapid control of hypercortisolism and is also used as a diagnostic tool. A key consideration for metyrapone is that it can increase androgen levels, leading to hirsutism and acne in women.
Levoketoconazole (Recorlev): This is another medication used to treat endogenous hypercortisolism in adults with Cushing's syndrome. It works by inhibiting cortisol production and is a newer option in this class of drugs.
Ketoconazole: Originally an antifungal agent, ketoconazole inhibits several steroid synthesis pathways, including cortisol production. It is a widely used option but requires careful monitoring due to potential hepatotoxicity (liver damage).

Glucocorticoid Receptor Blockers

For patients with specific related conditions, a different approach may be needed to counter cortisol's impact.

Mifepristone (Korlym): This medication is not designed to lower the amount of cortisol produced but rather to block the effects of excess cortisol on tissues. It is indicated for adult patients with Cushing's syndrome who have type 2 diabetes or glucose intolerance and have failed surgery or are not candidates for it. Because it blocks the receptors, it can't be monitored via standard cortisol level tests.

ACTH Secretion Inhibitors

In cases where the hypercortisolism is driven by excess ACTH from a pituitary tumor (Cushing's disease), these medications target the source of the hormonal signal.

Pasireotide (Signifor): Administered as a twice-daily shot, pasireotide works by mimicking the hormone somatostatin to inhibit ACTH release from pituitary tumors. While effective, it is associated with a high risk of hyperglycemia, which requires careful monitoring.
Cabergoline: This dopamine agonist has shown some success in controlling ACTH secretion in a subset of patients with Cushing's disease, but its efficacy can vary widely. It is generally better tolerated than pasireotide in terms of blood glucose control but requires cardiac valve monitoring at high doses.

Comparison of Cortisol-Lowering Medications


Feature	Osilodrostat (Isturisa)	Mifepristone (Korlym)	Pasireotide (Signifor)
Mechanism of Action	Inhibits cortisol synthesis via 11β-hydroxylase.	Blocks glucocorticoid receptors, preventing cortisol from binding.	Inhibits ACTH secretion from pituitary tumors.
Effect on Cortisol Levels	Reduces cortisol levels directly.	Does not lower circulating cortisol; blocks its effects.	Lowers circulating cortisol levels.
Indication	Endogenous hypercortisolemia in Cushing's.	Hyperglycemia in Cushing's syndrome with type 2 diabetes.	Cushing's disease.
Administration	Oral tablet.	Oral tablet, taken with a meal.	Subcutaneous injection twice daily.
Key Side Effects	QT prolongation, adrenal insufficiency, hypokalemia.	Hypokalemia, hypertension, endometrial thickening in women.	Hyperglycemia, diarrhea, nausea, headache.
Monitoring Challenges	Requires monitoring for QT prolongation and hypokalemia.	Cortisol levels cannot be used for monitoring efficacy.	Requires close monitoring of blood glucose levels.

Conclusion

High cortisol levels, particularly in the context of Cushing's syndrome, are a complex medical issue requiring precise management. What medication lowers cortisol levels? The answer depends on the underlying cause and the specific needs of the patient. Treatment can involve drugs that inhibit cortisol synthesis (osilodrostat, metyrapone), block its tissue effects (mifepristone), or inhibit ACTH production (pasireotide). A personalized treatment plan, under the strict supervision of an endocrinologist, is crucial for mitigating severe side effects and achieving the best possible outcome. Patients must never alter or discontinue these potent medications without a doctor's guidance. For more information on adrenal diseases, consult resources like the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Frequently Asked Questions

The most common condition requiring prescription cortisol-lowering medication is Cushing's syndrome, caused by chronic excess cortisol production.

Adrenal enzyme inhibitors like metyrapone block specific enzymes in the adrenal glands, which disrupts the final stages of cortisol production, leading to lower cortisol levels.

Mifepristone (Korlym) is a glucocorticoid receptor blocker, meaning it prevents cortisol from acting on tissues. It does not reduce the amount of cortisol in the body, unlike synthesis inhibitors.

No, prescription cortisol-lowering medications are potent drugs reserved for serious medical conditions like Cushing's syndrome and should not be used for managing everyday stress or anxiety.

Serious side effects can include adrenal insufficiency (very low cortisol), heart rhythm problems, high blood pressure, fluid retention, and liver damage.

Some supplements, like omega-3 fatty acids and prebiotics, are being researched for their potential to help modulate cortisol responses, but they are not a substitute for prescription medication for clinical hypercortisolism.

Medical therapy for Cushing's syndrome is generally not a cure. It is used to control cortisol levels and manage symptoms, but it may not fully reverse the condition.

Suddenly stopping these medications can cause hypocortisolism (very low cortisol levels), which can lead to severe side effects like adrenal insufficiency. Dosing must always be managed by a healthcare provider.