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Vaginal Moisturizers vs Vaginal Estradiol for Postmenopausal Vulvovaginal Symptoms


  • 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


  • 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


  • 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


  • 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