Why supplement with Dehydroepiandrosterone (DHEA) when levels are already elevated?

DHEA Supplementation in Elevated DHEA Levels

DHEA supplementation should not be given when DHEA levels are already elevated, as this contradicts the physiological purpose of replacement therapy and may lead to adverse effects.

Understanding DHEA Replacement Therapy

DHEA supplementation is primarily indicated in specific clinical scenarios where DHEA levels are deficient, not when they are elevated. The rationale behind DHEA therapy is based on the following principles:

Primary Adrenal Insufficiency Context

• In primary adrenal insufficiency (PAI), patients are deficient in adrenal androgen secretion, including DHEA 1
• DHEA supplementation is only considered in specific circumstances:
  • For female patients with PAI who have persistent lack of libido and/or low energy levels
  • Only after optimizing glucocorticoid and mineralocorticoid replacement
  • As a trial therapy (typically 6 months) that should only be continued if clinically effective 1, 2

Dosing and Monitoring

• When indicated, DHEA is typically given as:
  • 10-50 mg oral tablets, often 25 mg as a single daily dose
  • Dosing should be guided by serum DHEA sulphate (DHEAS), androstenedione, and testosterone levels
  • These levels should be maintained in the normal range when measured in the morning prior to DHEA ingestion 1

Why Not to Supplement When DHEA Is Already Elevated

1. Contradicts Replacement Principle: DHEA supplementation is intended as replacement therapy for deficiency states, not augmentation of already normal or elevated levels 2

2. Limited Evidence Base: There is only limited objective evidence of clinical benefit from large studies even in deficiency states 1

3. Potential Adverse Effects: Supplementing when levels are already elevated may lead to:

   • In women: Virilization, acne, hirsutism, and menstrual irregularities
   • In both sexes: Unpredictable effects on hormone balance
   • Unknown long-term effects on health 1, 3

4. Regulatory Concerns: DHEA is marketed as a dietary supplement with claims to "temporarily support the body to rebalance Adrenal and DHEA output" 4, but these claims lack substantial scientific support for use in individuals with already elevated levels

Evidence Quality Assessment

The recommendation against DHEA supplementation in elevated DHEA states is supported by:

• Guidelines from the Journal of Internal Medicine (2014) that specify DHEA is for replacement in deficiency states 1
• Praxis Medical Insights summary (2025) that clearly indicates DHEA supplementation is for persistent symptoms despite optimized conventional therapy in adrenal insufficiency 2
• Research evidence showing inconsistent results and highlighting that DHEA is not appropriate for all conditions 3

Clinical Approach to Elevated DHEA

Instead of supplementation, when DHEA levels are elevated:

1. Investigate the cause of elevated DHEA levels (could indicate adrenal hyperplasia, certain tumors, or medication effects)
2. Address the underlying condition rather than adding more DHEA
3. Consider alternative approaches for any symptoms the patient may be experiencing

Conclusion

Adding DHEA supplementation when levels are already elevated is physiologically unsound and potentially harmful. The therapeutic principle of DHEA supplementation is replacement in deficiency states only, particularly in female patients with adrenal insufficiency who have persistent symptoms despite optimized conventional therapy.