What is the treatment for low Dehydroepiandrosterone (DHEA) levels?

Treatment for Low DHEA Levels

For women with primary adrenal insufficiency and persistent low libido or energy despite optimized glucocorticoid/mineralocorticoid replacement, offer a 6-month trial of DHEA 25 mg daily; for isolated low DHEA without adrenal insufficiency, DHEA supplementation remains optional and should be used cautiously given limited long-term safety data. 1, 2

Diagnostic Workup Required First

Before treating low DHEA, you must determine the underlying cause:

• Measure paired morning cortisol, ACTH, basic metabolic panel, renin, and aldosterone to identify primary adrenal insufficiency 2, 3
• If results are indeterminate, perform standard-dose ACTH stimulation testing (0.25 mg cosyntropin with cortisol measured at 30/60 minutes; normal response >550 nmol/L) 1, 2
• Check 21-hydroxylase autoantibodies if primary adrenal insufficiency is confirmed 1
• In males, measure very long-chain fatty acids to exclude adrenoleukodystrophy 1

Treatment Algorithm

For Primary Adrenal Insufficiency with Low DHEA

Primary hormone replacement comes first—DHEA is always adjunctive:

• Start hydrocortisone 15-25 mg daily in split doses (first dose upon waking, last dose at least 6 hours before bedtime), using the lowest effective dose 1
• Add fludrocortisone 50-200 µg daily as a single dose for mineralocorticoid replacement 1
• Only after optimizing glucocorticoid/mineralocorticoid therapy, consider DHEA replacement 2, 3

DHEA supplementation protocol for women:

• Offer DHEA 25 mg once daily in the morning (dosing range 10-50 mg) to women with persistent lack of libido and/or low energy levels despite optimized primary replacement 1, 2, 3
• Monitor serum DHEA-sulfate, androstenedione, and testosterone levels in the morning before DHEA ingestion; maintain in normal range 1, 3
• Conduct a 6-month therapeutic trial and continue only if clinically effective 1, 3
• Watch for androgenic side effects: increased sebum production, facial acne, and hair changes 4

Important caveat: There is insufficient evidence to recommend routine DHEA replacement in all patients with primary adrenal insufficiency 1. The 2014 consensus statement from the Journal of Internal Medicine explicitly states this limitation, though it acknowledges a pragmatic approach for symptomatic women 1.

For Isolated Low DHEA Without Adrenal Insufficiency

DHEA supplementation is more controversial in this setting:

• DHEA 25-50 mg daily can be offered for women with sexual dysfunction or low energy, but evidence of benefit is inconsistent 2, 3, 4
• Establish baseline hormone levels before starting therapy 3
• Reassess clinical effectiveness after 6 months to determine continuation 3
• Use with particular caution as long-term effects are not fully established 1, 2, 3

Special Populations and Contraindications

Do not prescribe DHEA to:

• Men actively trying to conceive (suppresses normal sperm production) 3
• Cancer survivors on aromatase inhibitor therapy (use with extreme caution) 2, 3

In elderly patients:

• DHEA may improve physical/psychological well-being, muscle strength, bone density, and reduce body fat 5
• Lower DHEA levels correlate with functional limitations, depressive symptoms, and increased mortality in men 6
• However, large-scale randomized controlled trials are still needed before routine use can be recommended 4, 5

Alternative Treatment Options

If DHEA is contraindicated or ineffective for sexual dysfunction symptoms:

• Consider flibanserin for premenopausal women with female sexual dysfunction 2, 3
• Recommend pelvic floor muscle training which may improve sexual function 2, 3
• Use vaginal moisturizers and lubricants for vaginal symptoms 2, 3

Monitoring Protocol

During DHEA therapy:

• Measure morning DHEA-sulfate, androstenedione, and testosterone before daily dose to ensure levels remain in normal range 1, 3
• Assess clinical response at 6 months (libido, energy, well-being) 1, 3
• Monitor for androgenic side effects in women 4

Critical Pitfalls to Avoid

• Never use DHEA as monotherapy for primary adrenal insufficiency—glucocorticoid and mineralocorticoid replacement are life-saving and must be optimized first 2, 3
• Do not assume DHEA will benefit all patients—evidence shows inconsistent results, likely due to individual variability 4, 5
• Avoid long-term use without periodic reassessment given unknown long-term safety profile 1, 2
• Remember DHEA is regulated differently worldwide—it's a dietary supplement in the US but considered a hormone requiring prescription in many European countries 7