Is DHEA (dehydroepiandrosterone) supplementation indicated for a healthy adult without documented hormonal deficiency, and what dosing and monitoring are recommended?

DHEA Supplementation in Healthy Adults

DHEA supplementation is not indicated for healthy adults without documented hormonal deficiency, as there is no evidence of benefit on morbidity, mortality, or quality of life in this population. 1, 2

When DHEA Is NOT Indicated

Healthy individuals with normal adrenal function should not take DHEA supplements. The age-related decline in DHEA levels (decreasing approximately 2% per year after age 30) is a normal physiological process and does not constitute a disease state requiring treatment. 3, 4 While DHEA is marketed as an "anti-aging" supplement in the United States where it is classified as a nutritional supplement rather than a regulated hormone, no long-term health benefits have been demonstrated in replacement doses for healthy adults. 5

• The physiological decline in DHEA is universal but does not automatically warrant replacement therapy in asymptomatic individuals. 6
• Studies showing benefits have been limited to specific disease states, not healthy populations. 7
• The lack of FDA regulation as a nutritional supplement creates risks of inaccurate dosing and impurities. 5

Established Clinical Indications for DHEA

DHEA supplementation is appropriate only in specific clinical contexts:

Primary Adrenal Insufficiency in Women

Women with documented primary adrenal insufficiency who have persistent symptoms (low libido, low energy) despite optimized glucocorticoid and mineralocorticoid replacement should receive a 6-month trial of DHEA at 25 mg daily. 1, 2

• Measure morning serum cortisol (< 138 nmol/L indicates insufficiency) and plasma ACTH (> 2× upper limit confirms primary insufficiency). 1
• Check aldosterone and plasma renin activity to confirm mineralocorticoid deficiency. 1
• Initiate glucocorticoid (hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoid (fludrocortisone 0.05-0.2 mg daily) replacement first. 1
• Only after optimizing these replacements should DHEA be considered for persistent symptoms. 1, 2
• Continue DHEA only if clinically effective after the 6-month trial. 1, 2

Postmenopausal Women with Specific Symptoms

For postmenopausal women with vaginal atrophy, intravaginal DHEA is the most evidence-based indication, showing improvements in vaginal dryness, dyspareunia, and sexual function. 2

• The standard dose is 25 mg orally once daily in the morning, with a range of 10-50 mg based on response. 2
• Implement a 6-month trial period before determining long-term use. 2
• Evaluate treatment effect after 3-6 months and continue only with subjective improvement. 2
• Consider limiting therapy to 24 months due to limited long-term safety data. 2

Men with Primary Adrenal Insufficiency

Routine DHEA supplementation is NOT required in men with primary adrenal insufficiency because testicular testosterone production provides sufficient androgenic activity. 1

• A trial of DHEA may be considered only in men with persistent symptoms despite optimized glucocorticoid/mineralocorticoid therapy, though evidence of benefit is limited. 1
• Measure morning total and free testosterone (by equilibrium dialysis) as men with PAI frequently have concurrent hypogonadism. 1

Dosing and Monitoring When Indicated

Dosing Protocol

• Starting dose: 25 mg orally once daily in the morning. 1, 2
• Dose range: 10-50 mg daily based on clinical response. 1, 2
• Doses are guided by morning serum DHEA-S, androstenedione, and testosterone levels, which should be maintained in the normal range measured prior to DHEA ingestion. 1

Monitoring Requirements

• Measure baseline hormone levels (DHEA-S, androstenedione, testosterone) before initiating therapy. 2, 8
• Collect samples in the early morning (8-10 AM) for accurate interpretation. 1
• Monitor for signs of virilization (hirsutism, acne, voice deepening, clitoromegaly) indicating excessive androgen exposure requiring immediate dose adjustment. 2, 8
• Repeat measurements every 3-6 months until normalized or stable. 1
• For women on concurrent hormone therapy, recognize that DHEA and testosterone have additive effects and monitor total androgen levels carefully. 2

Contraindications and Safety Concerns

Absolute Contraindications

DHEA is contraindicated in breast cancer survivors due to potential risks of hormone-dependent cancers. 2

• Use with extreme caution in patients receiving aromatase inhibitor therapy. 2
• For women with hormone-positive breast cancer on aromatase inhibitors who have not responded to lubricants and moisturizers, vaginal DHEA may be offered only after thorough discussion of risks and benefits. 2

Red Flags Requiring Further Workup

• Clinical signs of virilization suggest excessive androgen exposure requiring dose reduction. 8
• DHEA-S levels markedly elevated warrant evaluation for adrenal pathology with adrenal CT or MRI. 1, 8
• Irregular menses or breakthrough bleeding may indicate hormonal imbalance requiring adjustment. 8

Common Pitfalls to Avoid

• Do not prescribe DHEA without establishing baseline hormone levels. 2
• Do not ignore signs of virilization, as these indicate excessive androgen exposure. 2, 8
• Do not assume age-related DHEA decline requires treatment in asymptomatic healthy adults. 5
• Do not use DHEA as a substitute for proper evaluation of underlying endocrine disorders. 1
• Do not prescribe long-term without periodic reassessment of clinical benefit. 2