What is the appropriate dosage and usage of Prasterone (dehydroepiandrosterone (DHEA)) for a postmenopausal woman with moderate to severe menopause symptoms or for a patient with adrenal insufficiency?

Prasterone (DHEA) Dosing and Usage

For postmenopausal women with sexual dysfunction, intravaginal prasterone 6.5 mg (0.5% ovule) daily is FDA-approved and most effective for treating moderate to severe dyspareunia, while oral DHEA 25-50 mg daily can be considered for women with adrenal insufficiency who have persistent low libido or energy despite optimized glucocorticoid and mineralocorticoid replacement. 1, 2

Postmenopausal Women with Sexual Dysfunction

Intravaginal Prasterone (Preferred Route)

• Intravaginal prasterone is FDA-approved specifically for moderate to severe dyspareunia due to vulvovaginal atrophy in postmenopausal women 1, 3
• The standard dose is 6.5 mg (0.5% ovule) inserted intravaginally once daily at bedtime 3
• This formulation significantly improves sexual desire, arousal, pain, and overall sexual function while maintaining serum hormone levels within normal postmenopausal ranges 4, 3
• Intravaginal DHEA does not carry an FDA boxed warning, unlike systemic estrogen therapies 3

Important Cautions for Cancer Survivors

• Use intravaginal DHEA with extreme caution in women receiving aromatase inhibitor therapy, as it increases circulating androgens that may interfere with AI activity 4
• The long-term safety of vaginal hormones has not been firmly established in survivors of estrogen-dependent cancers 4
• Despite these concerns, a randomized trial of 464 breast and gynecologic cancer survivors showed significant improvements in sexual function with vaginal DHEA 4

Women with Adrenal Insufficiency

Patient Selection Criteria

• DHEA supplementation should only be considered in women with primary or secondary adrenal insufficiency who have persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement 4, 2
• Baseline evaluation must confirm adequate cortisol and mineralocorticoid replacement before considering DHEA 4
• Measure baseline serum DHEA-sulfate (DHEAS), androstenedione, and testosterone levels prior to initiation 4, 2

Dosing Protocol

• Start with oral DHEA 25 mg once daily in the morning 2, 5
• The therapeutic range is 10-50 mg daily based on clinical response and hormone monitoring 4, 2
• A 6-month trial period is recommended to assess clinical effectiveness 4, 2
• Continue therapy only if clinically effective in improving symptoms 4, 2

Monitoring Requirements

• Measure serum DHEAS, androstenedione, and testosterone levels in the morning before DHEA ingestion 4, 2
• Target hormone levels should be maintained in the normal range for the patient's age 4, 2
• Reassess clinical effectiveness (libido, energy, quality of life) at 6 months 4, 2
• Monitor for androgenic side effects including acne, hirsutism, and voice changes 6, 5

Pharmacokinetics and Safety

Absorption and Metabolism

• Oral prasterone reaches peak serum concentration at 1.5-2 hours after administration 1
• After a single 200 mg dose, serum DHEAS levels increase 21-fold in women relative to baseline 1
• DHEA is sulfated to DHEAS in the intestine and liver, then converted peripherally to androgens and estrogens 1
• Elimination half-life in women is approximately 11 hours for DHEA and 12-27 hours for DHEAS 1

Adverse Effects

• The most common side effect is acne, occurring 3.77 times more frequently than placebo 6
• Androgenic effects (acne, hirsutism) are dose-dependent and generally mild to moderate 6, 5
• No serious adverse effects have been reported in clinical trials 5
• Oral doses up to 1.6 grams daily have not caused overdose in postmenopausal women 1

Long-Term Safety Considerations

• The long-term effects of DHEA replacement therapy are not fully known, so treatment should be used with caution 4, 2
• DHEA may be either chemoprotective or carcinogenic depending on the model, as it is converted to both androgenic and estrogenic metabolites 1
• DHEA should not be prescribed to men attempting to conceive, as it can suppress normal sperm production 2, 7

Clinical Evidence Summary

Quality of Life and Mood

• In women with adrenal insufficiency, DHEA shows small benefits in quality of life and mood but not anxiety 8
• No consistent beneficial effects have been observed for menopausal symptoms, cognition, or overall wellbeing in normal postmenopausal women 8
• A meta-analysis found no improvement in quality of life compared to placebo in general postmenopausal populations 6

Sexual Function

• DHEA modestly improves sexual function compared to placebo (SMD 0.31,95% CI 0.07-0.55) 6
• Intravaginal DHEA shows greater benefit for sexual function than oral administration 6
• Benefits are most pronounced in women with documented DHEA deficiency states 8, 9

Alternative Treatment Options

When DHEA is contraindicated or ineffective, consider:

• Vaginal estrogen remains the most effective treatment for vaginal dryness and dyspareunia in postmenopausal women 4
• Ospemifene (a SERM) is FDA-approved for dyspareunia in women without estrogen-dependent cancers 4
• Flibanserin is FDA-approved for hypoactive sexual desire disorder in premenopausal women 4, 2
• Pelvic floor physical therapy may improve sexual pain, arousal, and satisfaction 4, 2
• Vaginal moisturizers and lubricants provide symptomatic relief without hormonal effects 4, 2

Key Clinical Pitfalls to Avoid

• Do not initiate DHEA in women with adrenal insufficiency until glucocorticoid and mineralocorticoid replacement is optimized, as adding DHEA first could precipitate adrenal crisis 4
• Do not use TSH to monitor thyroid replacement in patients with secondary adrenal insufficiency, as TSH is unreliable in central hypothyroidism 4
• Do not continue DHEA beyond 6 months if no clinical benefit is observed 4, 2
• Do not use DHEA as first-line therapy for menopausal symptoms in women without adrenal insufficiency, as evidence of benefit is lacking 6, 8
• Ensure all patients with adrenal insufficiency receive education on stress dosing, emergency injectable hydrocortisone, and wear medical alert identification before considering DHEA supplementation 4