Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a double-blind, placebo-controlled trial

Menopause. 2017 Sep;24(9):1003-1010. doi: 10.1097/GME.0000000000000880.


Objective: To evaluate the response of the vaginal mucosa with TX-004HR and its correlation with vulvar and vaginal atrophy (VVA) symptoms, and whether visual examination is a useful measure for assessing VVA.

Methods: REJOICE was a 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of a vaginal, muco-adhesive, 17β-estradiol softgel capsule (TX-004HR 4, 10, and 25 μg) in postmenopausal women with VVA and moderate-to-severe dyspareunia. Treatments were self-administered vaginally once per day for 2 weeks, then twice per week for 10 weeks. The vagina was visually examined at baseline and at weeks 2, 6, 8, and 12; changes were evaluated using a 4-item scale for vaginal color, vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal secretions.

Results: Significant improvements were observed with all three TX-004HR doses versus placebo in vaginal color (least square mean score changes of -0.96 to -1.06 for TX-004HR doses vs -0.60 for placebo at week 12), epithelial integrity (-0.97 to -1.07 vs -0.60), epithelial surface thickness (-0.94 to -1.03 vs -0.61), and secretions (-1.01 to -1.06 vs -0.64) (P < 0.001 for all comparisons at all time points). Both Pearson's correlations and logistic regression receiver-operating characteristic curve analyses significantly correlated the sum of the individual visual assessment scores with dyspareunia (P < 0.0001) and vaginal dryness (P < 0.0001) at 12 weeks.

Conclusions: Greater improvements in the vaginal mucosa of postmenopausal women with VVA and moderate-to-severe dyspareunia were observed with TX-004HR versus placebo, and vaginal mucosa assessment scores correlated with vaginal symptoms of dyspareunia and dryness. Visual vaginal assessment by healthcare professionals is a useful measure for diagnosing VVA and assessing response to treatment.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravaginal
  • Aged
  • Atrophy / drug therapy
  • Color
  • Double-Blind Method
  • Dyspareunia / drug therapy
  • Epithelium / pathology
  • Estradiol / administration & dosage*
  • Female
  • Humans
  • Middle Aged
  • Mucous Membrane / pathology*
  • Placebos
  • Postmenopause*
  • ROC Curve
  • Treatment Outcome
  • Vagina / metabolism
  • Vagina / pathology*
  • Vaginal Diseases / drug therapy
  • Vulva / pathology*
  • Vulvar Diseases / drug therapy
  • Vulvar Diseases / pathology


  • Placebos
  • TX-004HR
  • Estradiol