What are the guidelines for DHEA (Dehydroepiandrosterone) sulfate supplementation?

DHEA Sulfate Supplementation Guidelines

Primary Recommendation for Women with Primary Adrenal Insufficiency

For women with primary adrenal insufficiency (PAI) who have persistent lack of libido and/or low energy levels despite optimized glucocorticoid and mineralocorticoid replacement, offer a 6-month trial of DHEA 25 mg orally once daily in the morning, guided by serum DHEA sulfate levels. 1

Specific Clinical Indications

Women with Primary Adrenal Insufficiency

• DHEA replacement is specifically indicated for female patients with PAI who experience severe androgen deficiency due to absent adrenal androgen secretion 1
• The typical starting dose is 25 mg orally as a single daily dose, with a range of 10-50 mg depending on individual response 1
• Treatment should be guided by monitoring serum DHEA sulfate (DHEAS), androstenedione, and testosterone levels, which should be maintained in the normal range when measured in the morning prior to DHEA ingestion 1

Postmenopausal Women with Vaginal Symptoms

• DHEA (prasterone) vaginal formulation is FDA-approved for treating vaginal dryness and pain with sexual activity in postmenopausal women 2, 3
• This formulation significantly improves sexual desire, arousal, pain, and overall sexual function 2, 3
• Vaginal DHEA is particularly useful for women on aromatase inhibitors who have not responded to non-hormonal treatments 3

Treatment Algorithm and Monitoring

Initial Assessment

• Confirm the diagnosis of PAI or postmenopausal status with appropriate hormonal deficiency 1
• Ensure glucocorticoid and mineralocorticoid replacement is optimized before adding DHEA 1
• Document baseline symptoms: libido, energy levels, sexual function 1, 4
• Obtain baseline morning DHEAS, androstenedione, and testosterone levels 1

Treatment Initiation

• Start with DHEA 25 mg orally once daily in the morning 1, 4
• For vaginal symptoms specifically, use vaginal DHEA (prasterone) formulation 2, 3
• Implement a 6-month trial period to assess clinical benefit 1, 4

Dose Adjustment

• Adjust dose between 10-50 mg daily based on clinical response and laboratory values 1, 4
• Monitor serum DHEAS, androstenedione, and testosterone levels in the morning before DHEA ingestion 1
• Target hormone levels should be maintained in the normal range for the patient's age and sex 1

Continuation Criteria

• Continue DHEA only if the patient reports subjective improvement in libido, energy, or sexual function after the 6-month trial 1, 4
• Discontinue if no clinical benefit is observed, as there is only limited objective evidence of benefit from large studies 1

Important Safety Considerations and Contraindications

Monitoring for Adverse Effects

• Monitor closely for signs of virilization: hirsutism, voice deepening, acne, or clitoral enlargement 4
• These signs indicate excessive androgen exposure and require immediate dose reduction or discontinuation 4
• Regular monitoring of hormone levels helps prevent over-replacement 1

Cancer-Related Precautions

• Use DHEA with extreme caution in patients with hormone-dependent cancers due to potential risks 2
• Avoid DHEA in patients on aromatase inhibitors (for oral systemic DHEA), as it increases circulating androgen levels that can be converted to estrogen 2
• The exception is vaginal DHEA formulation, which may be considered for aromatase inhibitor users with vaginal symptoms who have failed non-hormonal treatments 3
• DHEA should not be used by men with breast cancer 2

Long-Term Safety Unknown

• The long-term effects of DHEA replacement therapy in patients with PAI are not known, so use with caution 1
• This uncertainty necessitates careful patient selection and ongoing monitoring 1

Evidence Quality and Limitations

Strength of Evidence

• The recommendations are based on 2014 consensus guidelines from the Journal of Internal Medicine for PAI patients 1
• More recent 2025 guidelines from Praxis Medical Insights support DHEA use in postmenopausal women with specific indications 4, 2
• However, there is only limited objective evidence of clinical benefit from large studies 1

Key Limitation

• The pragmatic approach acknowledges that while physiologic rationale exists and some patients report benefit, robust clinical trial evidence demonstrating improved morbidity, mortality, or quality of life outcomes is lacking 1
• This explains why DHEA is offered as a trial rather than routine replacement 1

Common Clinical Pitfalls to Avoid

Inappropriate Patient Selection

• Do not prescribe DHEA without first optimizing glucocorticoid and mineralocorticoid replacement in PAI patients 1
• Symptoms of low energy may be due to inadequate cortisol or mineralocorticoid replacement rather than androgen deficiency 1

Inadequate Monitoring

• Do not prescribe DHEA without establishing baseline hormone levels, as this prevents appropriate dose titration 4
• Failure to monitor for virilization can lead to excessive androgen exposure 4

Continuing Without Benefit

• Do not continue DHEA indefinitely without documented clinical improvement after the 6-month trial 1, 4
• Given limited evidence of benefit, continuation should be based on clear patient-reported improvement 1

Ignoring Cancer History

• Do not ignore signs of virilization or history of hormone-dependent cancers when prescribing DHEA 4, 2
• These require immediate attention and potential discontinuation 4, 2

Special Populations

Pregnancy

• DHEA supplementation during pregnancy in PAI patients is not specifically addressed in guidelines 1
• Focus during pregnancy should be on adjusting glucocorticoid and mineralocorticoid doses as needed 1

Breast Cancer Survivors

• For vaginal symptoms in breast cancer survivors, non-hormonal options (moisturizers, lubricants) should be tried first 3
• Vaginal DHEA may be considered for those on aromatase inhibitors who have not responded to conservative measures, with thorough discussion of risks and benefits 3

Not Recommended for General Use

Healthy Aging

• DHEA supplementation is not recommended for general anti-aging purposes in healthy individuals 5, 6, 7, 8
• Despite declining DHEA levels with age, randomized controlled trials in healthy elderly individuals have yielded very few positive results 7
• There is no scientific evidence to recommend DHEA replacement in the general elderly population 7