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

Abstract

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.

The Women's EMPOWER Survey: Identifying Women's Perceptions on Vulvar and Vaginal Atrophy and Its Treatment

“…6 VVA affects up to 63% of postmenopausal women 10,11 and can have a detrimental effect on the quality of life and sexual function of women. 4,11 Although VVA can be diagnosed with physical examination findings combined with patient-reported symptom history, 12 previous US patient surveys have reported that health care professionals (HCPs) rarely initiate the conversation on VVA symptoms and that a little more than half (54%e62%) initiate conversations with their patients about their VVA symptoms. 7,9 Although some women initiate the conversation, many do not volunteer or discuss their symptoms because they feel embarrassed, believe that nothing can be done, or that it might be an inappropriate topic to discuss with their HCP.…”

Response letter to comments related to “The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women”

“…The 10-cm visual analogue scale (VAS) used in our study has been proposed as a patient reported outcome in the draft guidance of medical product development to support labeling claims by the US Food and Drug Administration. 4 Moreover, the VAS has been used as a tool to assess GSM symptoms in many studies, assessing other treatment options for GSM such as lubricants, vaginal estrogens etc [5][6][7][8][9]. 2) The second comment of Digesu et al 1 relates to the microbiological assessment of the vaginal flora.…”

Estradiol softgel inserts for the treatment of VVA symptoms: an expert opinion

“…Significantly more women using E2 had severity ratings of none to mild at week 12; vaginal color (79-84% vs 65% for placebo), vaginal epithelial integrity (83-89% vs 71%), vaginal epithelial surface thickness (78-83% vs 55%), and vaginal secretions (80-83% vs 61%) (all, p ≤ 0.0001 for each dose). All of these significant improvements were evident by week 2 [22]. Further, the sum of the individual visual assessment scores showed a significant linear correlation with the severity of dyspareunia and vaginal dryness at week 12 (both, p < 0.0001) [22].…”

“…All vaginal assessment parameters significantly improved from baseline to week 12 with all E2 doses versus placebo (Table 1) [22]. Significantly more women using E2 had severity ratings of none to mild at week 12; vaginal color (79-84% vs 65% for placebo), vaginal epithelial integrity (83-89% vs 71%), vaginal epithelial surface thickness (78-83% vs 55%), and vaginal secretions (80-83% vs 61%) (all, p ≤ 0.0001 for each dose).…”

“…Visual assessment of changes in the vaginal epithelium (n = 704) evaluated with treatment and in relation to VVA symptoms was another secondary endpoint of the REJOICE trial [22]. Examinations were performed using a 4-point scale (from 0 = none to 3 = severe) to assess vaginal color, vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal secretions [22].…”