TX-004HR clinically improves symptoms of vulvar and vaginal atrophy in postmenopausal women

Abstract

Objective: This study aimed to evaluate improvement of dyspareunia and associated vaginal dryness with a 17b-estradiol softgel vaginal insert (TX-004HR; TherapeuticsMD, Boca Raton, FL, USA) in women with postmenopausal vulvar and vaginal atrophy (VVA). Methods: Postmenopausal women with VVA and moderate to severe dyspareunia received TX-004HR (4, 10, or 25 lg) or placebo in the 12-week, randomized, double-blind, placebo-controlled, phase 3 REJOICE trial. Post hoc analyses examined improvement levels in dyspareunia and concurrent vaginal dryness with TX-004HR and assessed the effects of patient characteristics on vaginal dryness treatment. Results: Significantly more women treated with TX-004HR (all doses) than placebo had complete resolution or substantial improvement in dyspareunia or vaginal dryness (concurrent with dyspareunia) by 12 weeks, observed as early as week 2 with most doses. TX-004HR significantly improved both dyspareunia and vaginal dryness at least one level versus placebo by week 12 in women with both symptoms. Subgroup analyses showed TX-004HR improved vaginal dryness associated with dyspareunia regardless of age, body mass index, uterine status, prior pregnancy, and vaginal birth number. Conclusion: TX-004HR provided clinically meaningful improvements in dyspareunia and vaginal dryness associated with dyspareunia in postmenopausal women with VVA. Clinicians may be able to use this information when discussing patients' expectations regarding symptom improvement with the estradiol vaginal insert.

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

“…At baseline, the percentage of parabasal cells and vaginal pH were positively correlated with age and inversely correlated with BMI (all, p ≤ 0.002). Overall, treatment effects observed with the E2 inserts compared with placebo occurred regardless of age, BMI, uterine status, pregnancy history, and previous vaginal births, with most subgroup comparisons being statistically significant at weeks 2 and 12 [19,20].…”

“…For dyspareunia, significantly higher rates of substantial improvement were observed at week 12 with each E2 dose (41-55%) versus placebo (34%); and the two higher doses achieved significantly higher rates of complete resolution (32% and 31% vs placebo 20%) [19]. Similar results were observed for vaginal dryness, with significant substantial improvement observed at week 12 with each E2 dose compared with placebo (41-51% vs 31%) and significantly higher rates of complete resolution with all E2 doses (31-38% vs 16%) [19]. Approximately, 80% of women receiving any E2 dose had clinically meaningful improvement in both symptoms (p < 0.05) [19].…”

“…Subgroup analyses (secondary endpoints) were performed to determine if age (≤ 56, 57-61, and ≥ 62 years), BMI (≤ 24, 25-28, and ≥ 29 kg/m 2 ), uterine status (intact uterus or no intact uterus), pregnancy history (0 or ≥ 1), or number of vaginal births (0 or ≥ 1) had any effects on treatment outcomes (percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia or vaginal dryness [19]) [20]. Descriptive analyses…”

“…were used because the REJOICE study was not powered to evaluate these secondary endpoints [19,20]. At baseline, the percentage of parabasal cells and vaginal pH were positively correlated with age and inversely correlated with BMI (all, p ≤ 0.002).…”

“…Meaningful improvements in the VVA symptoms of dyspareunia and vaginal dryness were also evaluated (n = 704) [19]. Post hoc analyses examined the percentages of women with 'substantial' symptom (≥ 2 point) improvement, 'complete resolution' (score = 0), and 'clinically meaningful' (≥ 1 point) improvement for both dyspareunia and vaginal dryness; as well as predictors of improvement in vaginal dryness (concurrent with dyspareunia) [19].…”