How can I lower my cortisol levels?

How to Lower Cortisol Levels

If you have pathologically elevated cortisol from Cushing's disease or syndrome, medical treatment with steroidogenesis inhibitors (ketoconazole, metyrapone, or osilodrostat) is required, while lifestyle interventions including mindfulness meditation, regular exercise, and stress management techniques can effectively lower cortisol in individuals with stress-related elevations.

Clinical Context: Distinguish Pathologic from Physiologic Elevation

The approach to lowering cortisol depends entirely on whether elevation is pathologic (disease-related) or physiologic (stress/lifestyle-related):

For Pathologic Hypercortisolism (Cushing's Syndrome/Disease)

Medical management is essential and requires endocrinology consultation 1:

• Ketoconazole (400-1200 mg/day) is most commonly used due to easy availability and relatively tolerable toxicity profile, though it carries risk of hepatotoxicity requiring weekly ALT monitoring 1, 2
• Metyrapone provides rapid cortisol reduction (within hours) by inhibiting 11-beta-hydroxylation in the adrenal cortex 1, 3
• Osilodrostat offers high efficacy with twice-daily dosing and rapid control in the majority of patients 1

Critical monitoring requirements 2:

• Baseline liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) before starting ketoconazole
• Weekly ALT monitoring throughout treatment duration
• Interrupt treatment if ALT exceeds upper limit of normal or increases 30% above baseline

Adrenal insufficiency risk 3:

• Metyrapone can induce acute adrenal insufficiency (nausea, vomiting, abdominal pain, hypotension)
• Patients require education on stress dosing and medical alert identification
• Endocrine consultation is mandatory before surgery or high-stress treatments 1

For Physiologic/Stress-Related Cortisol Elevation

Lifestyle and behavioral interventions are first-line and highly effective:

Mindfulness and Meditation (Strongest Evidence)

• Mindfulness meditation significantly reduces serum cortisol levels with a medium-to-large effect size (g = 0.345) 4
• Even short-term interventions (4 days) can lower cortisol from 381.93 nmol/L to 306.38 nmol/L 5
• Cortisol awakening response shows the largest reductions (g = 0.644) compared to diurnal measurements 4

Exercise Programs

• Physical exercise produces marked reductions in morning cortisol levels and flattens the diurnal cortisol slope 6
• High-intensity interval training (HIIT) combined with dietary advice shows statistically significant cortisol reduction (p = 0.006) 7
• Exercise effects are superior to cognitive behavioral therapy alone for cortisol normalization 6

Relaxation Techniques

• Relaxation interventions demonstrate strong efficacy (g = 0.347) comparable to mindfulness 4
• Active participation in stress management programs outperforms passive approaches (g = 0.477 vs g = 0.129) 4

Lifestyle Modification Considerations

• Avoid alcohol and smoking, as both significantly elevate cortisol levels independent of stress 8
• Optimize sleep quality and duration, as sleep deprivation increases cortisol secretion 8
• Nutritional factors including adequate protein intake and avoiding excessive caffeine can influence cortisol regulation 8

Common Pitfalls to Avoid

Do not use talking therapies as primary cortisol-lowering interventions - they show minimal effect sizes (g = 0.107) and are non-significant for cortisol reduction 4

Do not restart ketoconazole after hepatotoxicity - hepatotoxicity has been reported with rechallenge and can be fatal 2

Do not exceed recommended ketoconazole doses (200-400 mg daily) as higher doses increase adrenal suppression risk 2

Do not assess cortisol in shift workers or those with disrupted sleep-wake cycles using late-night salivary cortisol, as circadian disruption invalidates results 1

Monitoring and Follow-up

For medical management 1:

• Morning ACTH and cortisol levels to distinguish primary from secondary causes
• Electrolytes (sodium, potassium) to assess mineralocorticoid effects
• Consider ACTH stimulation testing for indeterminate results (cortisol 3-15 mg/dL)

For lifestyle interventions 4:

• Cortisol awakening response provides the most sensitive measure of intervention effectiveness
• Effects typically manifest within 2-4 months of consistent intervention
• Combination approaches (diet + exercise) show superior outcomes to single interventions 7