Does Dehydroepiandrosterone (DHEA) lower cortisol levels?

DHEA's Effect on Cortisol Levels

DHEA supplementation can lower cortisol levels, particularly in women, though the evidence is limited and the effect may vary between individuals. 1

Relationship Between DHEA and Cortisol

• DHEA (Dehydroepiandrosterone) is not a hormone itself but an important prohormone secreted by the adrenal glands in large amounts in humans and other primates 2
• DHEA and cortisol are both end products of the adrenal stress response, often working in opposing physiological actions 3
• The relationship between DHEA and cortisol is complex, with evidence suggesting they may have counterbalancing effects 3

Research Evidence on DHEA's Effect on Cortisol

• A single-blind placebo-controlled crossover study found that DHEA administration (200 mg daily) resulted in decreased plasma cortisol concentrations in healthy older adults 1
• The cortisol-lowering effect was more pronounced in women than in men, with significant reductions observed after multiple days of DHEA administration 1
• In a different study, a 100 mg daily dose of DHEA for 6 months increased serum DHEA levels to those of young adults without altering cortisol levels, thus increasing the DHEA/cortisol ratio 4

Clinical Implications

• DHEA replacement is considered in clinical guidelines primarily for women with primary adrenal insufficiency who have persistent low libido and/or energy levels despite optimized glucocorticoid and mineralocorticoid replacement 5
• Guidelines suggest DHEA supplementation (10-50 mg daily, often 25 mg) for women with adrenal insufficiency, guided by serum DHEA sulfate, androstenedione, and testosterone levels 5
• The American Society of Clinical Oncology guidelines note that DHEA replacement is controversial but may be considered in specific clinical scenarios 5

Dosing and Monitoring

• When prescribed, DHEA is typically administered as a single daily dose of 10-50 mg (often 25 mg) 5
• Monitoring should include morning measurements of DHEA sulfate, androstenedione, and testosterone levels, which should be maintained in the normal range 5
• A pragmatic approach is to offer female patients with persistent symptoms a 6-month trial of DHEA replacement, which can be continued if clinically effective 5

Important Considerations and Caveats

• Long-term effects of DHEA replacement therapy are not well established, so such regimens should be used with caution 5
• The evidence for clinical benefit from large studies is limited 5
• Recent research suggests DHEA may act as a protective factor against depression when cortisol levels are high, indicating a potential moderating role in stress-related conditions 6
• Individual responses to DHEA supplementation may vary, with gender-specific differences observed in several studies 1, 4

Clinical Decision-Making

• DHEA supplementation should be considered primarily for women with confirmed adrenal insufficiency who have persistent symptoms despite optimal standard hormone replacement 5
• Baseline and follow-up hormone measurements should guide dosing decisions 5
• The potential cortisol-lowering effect may be beneficial in some clinical scenarios but should be monitored, particularly in patients with adrenal insufficiency 1, 3