What is the typical dose and usage of Prasterone (dehydroepiandrosterone (DHEA))?

Prasterone (DHEA) Dosing, Mechanism, and Clinical Use

For women with primary adrenal insufficiency experiencing persistent low libido or low energy despite optimized glucocorticoid and mineralocorticoid replacement, start prasterone 25 mg orally once daily in the morning, with a dose range of 10-50 mg guided by serum hormone levels. 1

Mechanism of Action

Prasterone (dehydroepiandrosterone/DHEA) functions as a prohormone that undergoes peripheral conversion to active sex steroids:

• Metabolic conversion: DHEA is sulfated to DHEA-sulfate (DHEAS) in the intestine and liver by sulfotransferases, then converted in peripheral tissues to androstenedione, testosterone, dihydrotestosterone, estradiol, estrone, and estriol 2
• Neurosteroid activity: DHEAS penetrates the blood-brain barrier (cerebrospinal fluid levels reach 0.2-5% of plasma levels) and may act as a neurosteroid with direct brain receptor affinity 2
• Androgen replacement: In women with adrenal insufficiency, DHEA compensates for the complete loss of adrenal androgen production 1

Standard Dosing Protocol

Initial Dosing

• Starting dose: 25 mg orally once daily, taken in the morning 1, 3, 4
• Dose range: 10-50 mg daily based on clinical response and hormone monitoring 1, 3, 4
• Higher doses: The FDA-approved formulation uses 200 mg daily for specific indications (systemic lupus erythematosus), though this exceeds typical replacement doses 2

Pharmacokinetics

• Time to peak: Reaches peak serum concentration at 1.5-2 hours after oral administration 2
• Half-life: Approximately 11 hours in young women, 7 hours in elderly men, with progressive decline in elderly women (12 hours day 1, declining to 7 hours by day 15) 2
• No accumulation: Daily administration does not result in steroid accumulation over 2 weeks 2, 5
• Protein binding: 10-20% of DHEA is protein-bound; 80-90% of DHEAS is protein-bound 2

Clinical Indications

Primary Indication: Adrenal Insufficiency in Women

Offer a 6-month trial of DHEA to female patients with primary adrenal insufficiency who have persistent lack of libido and/or low energy levels despite optimized glucocorticoid and mineralocorticoid replacement. 1, 3, 4

• Continue therapy only if clinically effective after the 6-month trial 1, 3, 4
• Evidence of clinical benefit from large studies remains limited 1

Secondary Indication: Female Sexual Dysfunction

• DHEA supplementation has demonstrated significant improvements in sexual desire, arousal, pain, and overall sexual function in clinical trials involving female cancer survivors 3, 4
• Typical dosing remains 10-50 mg daily, with 25 mg as the common starting dose 3, 4

Contraindications and Cautions

• Not recommended in men trying to conceive: DHEA can suppress normal sperm production 3, 4
• Use with caution in cancer survivors on aromatase inhibitors: Vaginal DHEA increases circulating androgen levels 3, 4
• Not established for pregnancy or lactation: Safety and effectiveness have not been established 2
• Not recommended in pediatric patients: Safety and effectiveness have not been established 2
• Athletic anti-doping: DHEA use is prohibited by certain athletic anti-doping regulations 2

Monitoring Protocol

Baseline Assessment

Establish baseline hormone levels before initiating therapy 3, 4:

• Serum DHEA-sulfate (DHEAS)
• Androstenedione
• Testosterone

Follow-up Monitoring

• Timing: Measure hormone levels in the morning prior to DHEA ingestion 1, 3, 4
• Target: Maintain serum DHEAS, androstenedione, and testosterone in the normal range 1, 3, 4
• Clinical assessment: Evaluate effectiveness at 6 months to determine whether to continue therapy 1, 3, 4

Expected Hormonal Changes

With 50 mg daily dosing, plasma DHEAS increases to levels within the normal range for young adults 6, 5. After a single 200 mg dose, mean serum DHEAS levels increase 5-fold in men (to 7 mcg/mL) and 21-fold in women (to 7.5 mcg/mL) relative to baseline 2.

Safety Considerations and Long-Term Use

Duration of Therapy

• Continue until natural menopause age: For women with adrenal insufficiency, DHEA should be continued until the average age of spontaneous menopause (45-55 years) 1
• Long-term effects unknown: The long-term effects of DHEA replacement therapy are not fully known, so use with caution 1, 3, 4

Metabolic Effects

Low-dose DHEA (25 mg daily) in postmenopausal women increases plasma levels of androgens, estrogens, progestogens, and neurosteroids (particularly allopregnanolone), while reducing gonadotropins 7. These changes occur without affecting endometrial thickness 7.

Reported Benefits

• Improvements in mood, fatigue, general well-being, and sexual function 6
• Bone turnover improvement selectively in women >70 years old 8
• Increased libido parameters in older women 8
• Skin status improvement (hydration, epidermal thickness, sebum production, pigmentation), particularly in women 8

Side Effects

Androgenic side effects on skin and hair appear moderate and acceptable at replacement doses 6. No worrying transformation to excessive androgens or estrogens has been recorded at 25-50 mg daily doses 5.

Overdose

Oral DHEA up to 1.6 grams per day has not provoked overdose in postmenopausal women 2. In case of suspected overdose, discontinue DHEA and treat symptomatically 2.

Practical Clinical Algorithm

1. Confirm diagnosis: Verify primary adrenal insufficiency with appropriate testing 4
2. Optimize primary replacement: Ensure glucocorticoid and mineralocorticoid replacement is optimized before considering DHEA 1, 4
3. Assess symptoms: Identify persistent lack of libido and/or low energy despite optimized replacement 1, 3, 4
4. Obtain baseline labs: Measure morning DHEAS, androstenedione, and testosterone 1, 3, 4
5. Initiate trial: Start DHEA 25 mg orally once daily in the morning 1, 3, 4
6. Monitor response: Check morning hormone levels (before DHEA ingestion) and adjust dose to maintain normal range 1, 3, 4
7. Assess at 6 months: Continue only if clinically effective 1, 3, 4
8. Long-term management: Continue until natural menopause age with periodic reassessment 1

Common Pitfalls to Avoid

• Starting DHEA before optimizing primary replacement: Always optimize glucocorticoid and mineralocorticoid replacement first 1, 4
• Measuring hormone levels at wrong time: Always measure in the morning before DHEA ingestion for accurate assessment 1, 3, 4
• Continuing ineffective therapy: Discontinue after 6 months if no clinical benefit is observed 1, 3, 4
• Using in men attempting conception: DHEA suppresses normal sperm production 3, 4
• Inadequate monitoring in cancer survivors: Exercise particular caution with aromatase inhibitor therapy due to increased circulating androgens 3, 4