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

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, 17b-estradiol softgel capsule (TX-004HR4, 10, and 25 mu g) in postmenopausalwomen with VVA andmoderate-to-severe dyspareunia. Treatmentswere self-administered vaginally once per day for 2weeks, then twice per week for 10 weeks. The vagina was visually examined at baseline and atweeks 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 moderateto- 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.