BACKGROUND AND PURPOSE:

• Vulvovaginal symptoms, including dryness and dyspareunia are common in postmenopausal women and are part of the Genitourinary Syndrome of Menopause (GSM)
• Mitchel et al. (JAMA Int Med,  2018) compared the effectiveness of a low-dose vaginal estradiol tablet, a vaginal moisturizer, and placebo, as treatments for moderate-to-severe postmenopausal vulvovaginal symptoms

METHODS:

• 12-week, randomized, multicenter clinical trial
• Participants: Patients with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration
  • Age 45 to 70 years, at least 2 years since last menses, report of at least 1 moderate to severe symptom at least weekly within the past 30 days or
  • Pain with penetration at least once monthly
• Women received either (1:1:1)
  • 10-µcg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week)
  • Placebo tablet plus vaginal moisturizer
  • Dual placebo
• Moisturizer ingredients
  • Purified water, glycerin, mineral oil, polycarbophil, carbomer homopolymer type B, hydrogenated palm oil glyceride, sorbic acid, and sodium hydroxide
    • Placebo gel ingredient was hydroxyethylcellulose gel
  • Primary outcome: Decrease in severity of most bothersome symptoms (MBS)
  • Secondary outcomes: Composite vaginal symptom score | Female Sexual Function Index (FSFI) score | modified Female Sexual Distress Score-Revised item 1 treatment satisfaction and meaningful benefit | Vaginal Maturation Index | vaginal pH

RESULTS:

• Data was collected from 302 women; mean of 61 years
  • Primarily white, college educated, and sexually active
  • Tablet plus placebo moisturizer (n = 102)
  • Placebo plus moisturizer (n = 100)
  • Dual placebo (n = 100)
• The most commonly reported MBS
  • Pain with vaginal penetration in 60%
  • Vulvovaginal dryness in 21%
• All treatment groups had similar mean reductions in MBS severity over 12 weeks and no significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo
  • Estradiol: −1.4 (95% CI, −1.6 to −1.2)
  • Moisturizer: −1.2 (95% CI, −1.4 to −1.0)
  • Placebo: −1.3 (95% CI, −1.5 to −1.1)
• There was no statistical difference in mean total FSFI improvement between estradiol (P=.64) and moisturizer (P=.17) compared with placebo
  • Estradiol: 5.4; 95% CI, 4.0 to 6.9
  • Moisturizer: 3.1; 95% CI, 1.7 to 4.5
  • Placebo: 4.5; 95% CI, 2.8 to 6.1

CONCLUSION:

• Neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer reduced postmenopausal vulvovaginal symptoms compared to placebo
• Estradiol tablets performed similarly to existing literature for vaginal estrogen, newly approved vaginal DHEA, and ospemifene, a selective estrogen receptor modulator
• Placebo gel worked better than in previous studies, not linked to vaginal pH
  • Other factors beyond local vaginal environment may play a role
• Authors suggest that

Our results suggest that most women can achieve greater than 50% reduction in symptom severity with regular, consistent use of a vaginal gel with lubricant properties and do not see added symptom improvement with vaginal estradiol.

Learn More – Primary Sources:

Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal SymptomsA Randomized Clinical Trial

Related ObG Topics:

Genitourinary Syndrome of Menopause: New Name, Old Problem

What and When to Tell Patients About Lubricants?

Treating Postmenopausal Vaginal Atrophy When Estrogen is Not an Option

Prasterone for Vulvovaginal Atrophy – What is it and How to Prescribe