What is vaginal DHEA (Dehydroepiandrosterone)?

Vaginal DHEA (Prasterone)

Vaginal DHEA (prasterone) is an FDA-approved treatment for moderate to severe dyspareunia in postmenopausal women that works by converting locally into estrogens and androgens in vaginal tissue, improving vaginal health with minimal systemic effects. 1

What is Vaginal DHEA?

Vaginal DHEA (dehydroepiandrosterone), marketed as prasterone, is a synthetic equivalent to endogenous DHEA that serves as a precursor hormone. When applied intravaginally:

• It is converted locally within vaginal tissues into both estrogens and androgens 2
• It addresses symptoms of vulvovaginal atrophy without significantly affecting serum hormone levels 3
• It is applied daily as a vaginal insert (6.5mg dose) 2
• Unlike other menopausal hormone therapies, it does not carry an FDA boxed warning 3

Clinical Benefits

Vaginal DHEA has demonstrated significant improvements in:

• Vaginal dryness (improvement by 1.44 severity score units from baseline) 2
• Pain during sexual activity (reduction by 1.42 severity score units from baseline) 2
• Sexual function across all domains:
  • Desire (+49.0% over placebo)
  • Arousal (+56.8% over placebo)
  • Lubrication (+36.1% over placebo)
  • Orgasm (+33.0% over placebo)
  • Satisfaction (+48.3% over placebo)
  • Pain reduction (+39.2% over placebo) 4
• Vaginal pH (decreased by 0.66 pH unit over placebo) 2
• Vaginal cellular health (decreased parabasal cells by 27.7% and increased superficial cells by 8.44% over placebo) 2

Mechanism of Action

Vaginal DHEA works through "intracrinology" - a process where:

• The medication is metabolized directly in vaginal tissues into estrogens and androgens
• These hormones act locally to improve vaginal epithelium, blood flow, and lubrication
• Serum hormone levels remain within normal postmenopausal ranges 2, 5

Clinical Context and Usage

Vaginal DHEA fits into treatment algorithms for dyspareunia as follows:

1. First-line treatments: hormone-free lubricants and moisturizers
2. Second-line treatments (when non-hormonal measures are ineffective):
   • Low-dose vaginal estrogen
   • Vaginal DHEA (prasterone) - particularly valuable for women concerned about systemic estrogen effects 1

Advantages and Considerations

Advantages:

• Minimal systemic absorption with hormone levels remaining within normal postmenopausal range 2
• No FDA boxed warning, unlike systemic hormone therapies 3
• Effective for improving multiple aspects of sexual function 4
• May be appropriate for women with concerns about estrogen therapy 1

Considerations:

• Requires daily application (compared to some vaginal estrogen products that require 2-3 applications weekly) 6
• Most common side effect is vaginal discharge (reported in approximately 6% of users) due to melting of the vehicle at body temperature 2
• Long-term safety data beyond clinical trials is still accumulating 6

Clinical Pearls

• Vaginal DHEA represents an alternative approach for treating dyspareunia in women who cannot or prefer not to use estrogen-based therapies
• The local action mechanism provides targeted relief with minimal systemic effects
• It addresses both the physical and sexual function aspects of genitourinary syndrome of menopause
• Regular application is essential for maintaining benefits

Vaginal DHEA offers a physiologically-based approach to treating vaginal atrophy by leveraging the body's own steroid conversion pathways to improve vaginal health without significantly altering systemic hormone levels.