What are the treatment options for an adult over 40 with confirmed low Dehydroepiandrosterone (DHEA) levels and symptoms suggestive of adrenal insufficiency or androgen deficiency?

Treatment of Low DHEA in Adults Over 40

DHEA replacement should be considered in adults over 40 with confirmed low DHEA levels and symptoms of adrenal insufficiency or androgen deficiency, particularly in women with low libido, fatigue, or poor energy who are already adequately replaced on glucocorticoid and mineralocorticoid therapy. 1

Initial Diagnostic Approach

Before initiating DHEA replacement, you must first confirm adequate replacement of primary hormones:

• Verify glucocorticoid adequacy by assessing for morning fatigue, salt cravings, lightheadedness, and whether symptoms improve after taking hydrocortisone 1
• Evaluate mineralocorticoid status by checking for salt cravings, orthostatic hypotension, and peripheral edema 1
• Measure baseline morning serum DHEA sulfate, androstenedione, and testosterone levels before starting therapy 1
• Evaluate ACTH and cortisol levels (AM) to distinguish primary from secondary adrenal insufficiency 2

Critical pitfall: Do not start DHEA replacement until glucocorticoid and mineralocorticoid replacement are optimized, as other hormones can accelerate cortisol clearance and precipitate adrenal crisis 2

DHEA Replacement Protocol

Dosing Strategy

Start with DHEA 25 mg once daily in the morning for a 6-month trial 1. This is the evidence-based dose that has demonstrated clinical benefits in multiple studies 3, 4, 5.

• The target is to maintain DHEA sulfate levels in the normal range for premenopausal women 1
• Recheck DHEA sulfate, androstenedione, and testosterone levels at 3 months and adjust dose as needed 1
• Assess clinical efficacy at 6 months to decide whether to continue therapy 1

Expected Benefits

DHEA replacement has demonstrated improvements in:

• Quality of life, mood, and general well-being in patients with adrenal insufficiency 3, 4, 5
• Sexual function and libido, particularly in women 1, 4, 6
• Energy levels and fatigue 1, 4
• Body composition and muscle strength 4
• Menstrual patterns in women with shortened cycles due to androgen deficiency 1

Evidence Quality and Controversies

The evidence for DHEA replacement remains controversial but is supported by guideline recommendations 2. The ASCO guidelines (2021) explicitly state that "DHEA replacement is controversial but deficiency can be tested and replacement considered in women with low libido and/or energy who are judged to be otherwise well replaced" 2.

The inconsistency in published data stems from:

• Variable dosing protocols across studies 3, 4
• Different patient populations studied 3, 6
• Rapid metabolism of DHEA making measurement challenging 4
• Lack of recent large-scale randomized controlled trials 3

However, the safety profile is excellent: Despite widespread use as a supplement, no serious adverse events related to DHEA have been reported in the world literature or FDA monitoring 7

Monitoring Strategy

Follow-up Timeline

• 2-4 weeks: Reassess symptoms after any glucocorticoid or mineralocorticoid adjustments 1
• 3 months: Check morning DHEAS, androstenedione, and testosterone levels 1
• 6 months: Make final decision on continuing DHEA based on clinical efficacy 1

Side Effects to Monitor

• Androgenic effects: Acne, hirsutism, hair changes (typically moderate and acceptable) 5
• Hormonal imbalances: Monitor for signs of excess androgen conversion 1

Special Considerations

Drug Interactions

Avoid NSAIDs in patients on fludrocortisone, as they interact and may worsen symptoms 1. This is particularly important if joint symptoms are present.

Patient Education Requirements

All patients with adrenal insufficiency require education on:

• Stress dosing protocols: Double oral glucocorticoid dose for 24-48 hours during acute illness 1
• Emergency injectable use and when to seek medical attention 2
• Medical alert bracelet or necklace to trigger stress dose corticosteroids by emergency personnel 2

Gender Differences

DHEA replacement shows more measurable benefits in women than men 7. In men, testicular androgens continue throughout life, making DHEA deficiency less clinically significant 7. However, adrenal DHEA contributes approximately 40% of the total androgen pool in 65-75-year-old men 7.

When NOT to Replace DHEA

Do not initiate DHEA replacement in:

• Patients with inadequately controlled glucocorticoid or mineralocorticoid replacement 1
• Patients with contraindications to androgen therapy (prostate cancer, breast cancer, history of DVT) 2
• Asymptomatic patients with low DHEA who are otherwise functioning well 2