Vaginal softgel benefits older women with vulvovaginal atrophy

Use of the self-administered TX-004HR – an applicator-free, ultra-low-dose, 17β-oestradiol softgel vaginal insert – led to significant improvements in the symptoms of vulvovaginal atrophy (VVA) such as moderate-to-severe dyspareunia and vaginal dryness in postmenopausal women aged >60 years, according to updated results from the phase III REJOICE trial presented at NAMS 2020.

VVA is a chronic genitourinary condition affecting more than 30 million women in the US, which can be bothersome and can progressively worsen if left untreated. [Menopause 2013;20:888-902] “[Given the] ageing … population and increasing longevity, this burden may last for over one-third of their lives,” said the researchers.

Initial findings of the REJOICE trial showed that TX-004HR markedly oestrogenized the vaginal tissue, improved symptoms of dyspareunia and vaginal dryness compared with placebo, and proved to be safe and well-tolerated in menopausal women with moderate-to-severe dyspareunia. [Menopause 2017;24:409-416] This led to the US FDA approval in 2018 of the 4- and 10-μg doses of TX-004HR for the management of moderate-to-severe dyspareunia due to menopause. [ir.therapeuticsmd.com/news-releases/news-release-details/therapeuticsmd-announces-fda-approval-tx-004hr-imvexxytm, accessed October 12, 2020] However, evidence on its impact on older women (aged >60 years) is lacking, noted the researchers.

The team therefore sought to evaluate the efficacy of TX-004HR in postmenopausal women with VVA (defined as ≤5 percent superficial cells on vaginal cytological smear and vaginal pH of >5.0) and moderate-to-severe dyspareunia. Of the 764 women (mean age 59 years) in the REJOICE cohort, 295 were aged >60 years. Participants were randomized to receive the TX-004HR either at a dose of 4, 10, or 25 µg, or a placebo vaginal insert, for 12 weeks. The vaginal insert was to be administered daily for 2 weeks followed by a twice-weekly dosing. [NAMS 2020, abstract P-11]

Beginning week 8, compared with placebo use, the administration of TX-004HR – regardless of dose – led to significant improvements in the severity of dyspareunia (p<0.05 for all doses).

Weeks 6 and 12 saw significant improvements in vaginal dryness with TX-004HR 4 µg vs placebo at (p<0.05 for both timepoints).

Apart from symptomatic relief, corresponding cytologic improvements were also observed with TX-004HR vs placebo, as reflected by the significant increases in the percentage of superficial cells (p<0.05), reductions in the percentage of parabasal cells (p<0.0001), and drops in vaginal pH from baseline (p<0.0001). These results were consistently observed across all timepoints (weeks 2, 6, 8, and 12).

Marked improvements were also noted in terms of visual parameters (ie, vaginal colour, vaginal secretions, surface thickness, epithelial integrity) with all TX-004HR doses compared with placebo across all timepoints (p<0.05 for all).

The current results reinforce the initial findings of REJOICE and support the efficacy of TX-004HR in improving the objective measures of VVA, including vaginal cytology and pH, in this setting, said the researchers.