Single hyaluronic acid jab may be beneficial in managing vulvovaginal atrophy

A single injection of cross-linked hyaluronic acid appears to help reduce vulvovaginal symptoms (VVA) and improve sexual dysfunction in postmenopausal women, as shown in a study.

At the 12-week follow-up, participants who received the hyaluronic acid injection had significantly greater reductions in the severity score for the most bothersome symptom (MBS), the primary outcome, compared with those who received the placebo injection (between-group difference, −0.58, 95 percent confidence interval [CI], –1.01 to −0.16; p=0.008). [Maturitas 2025;197:108264]

More than half of the participants in the hyaluronic acid group had an MBS score of ≤1, indicating no or mild symptoms, as opposed to less than a quarter in the placebo group (52.9 percent vs 22.2 percent; p=0.003).

Results for other VVA symptoms graded as moderate to severe at baseline also favoured the hyaluronic acid injection, which yielded greater improvements in dryness sensation (between-group difference, −0.87, 95 percent CI, −1.27 to −0.47; p<0.001) and dyspareunia (between-group difference, −0.65, 95 percent CI, −1.09 to −0.21; p=0.004) relative to placebo.

Accordingly, participants who received the hyaluronic injection reported a significantly greater improvement in sexual function score compared with those who received the placebo injection. The between-group difference in the Female Sexual Function Index score at week 12 was 3.81 (95 percent CI, 0.91–6.72; p=0.011).

While the exact mechanistic pathways by which hyaluronic acid works remain unclear, researchers postulated that its positive effects are largely due to its water-binding and hydrating properties.

“It provides hydration by binding water molecules to the mucosa surface… Cross-linking the hyaluronic acid gel has a stabilizing effect, allowing for slow degradation, thereby providing hydration for a longer duration,” they explained. [J Sex Med 2021;18:156-166; Arch Dermatol 2007;143:155163]

Well tolerated

While injecting hyaluronic acid into the vaginal area might be deemed invasive, the current study demonstrates that treatment is safe and causes limited pain, the researchers noted.

The incidence of treatment-related adverse events (AEs) was low and similar between the hyaluronic acid and placebo groups (11.3 percent vs 13.5 percent). Most AEs were mild or moderate in intensity, with only one severe event of vulvovaginal pruritus occurring in the hyaluronic acid group.

Hyaluronic acid-related AEs included cystitis and mild-to-moderate pain after injection (ie, vulvovaginal pain, injection site pain), which resolved quickly spontaneously. Only one case of serious AE was reported—a back pain that was not related to hyaluronic acid treatment.

Suitable option

The findings demonstrate that the resorbable cross-linked hyaluronic acid gel approved for vaginal mucosa injection is “a suitable management option for moderate to severe vulvovaginal atrophy symptoms,” according to the researchers.

The injectable approach overcomes some of the limitations associated with topical treatment options, such as poor compliance, variable dosage, lack of spontaneity during intercourse, and daily topical applications, they continued. “Importantly, it provides an alternative option for patients with contraindications to oestrogen-based therapies, like breast cancer.”

Given that breast cancer is the most commonly diagnosed cancer worldwide, with up to 70 percent of survivors having been reported to experience VVA symptoms, breast cancer patients represent a large number of patients for whom nonhormonal therapies should be the first-choice management option, the researchers said. They stressed that hyaluronic acid injections can potentially improve compliance with adjuvant hormone therapy in this population by alleviating treatment-induced vaginal dryness and dyspareunia. [Drugs Aging 2019;36:897-908; Menopause 2019;26:124-131; Bull Cancer 2024;111:347-355; Oncologie 2019;5:202-207]

Study details

In the study, 117 postmenopausal women with symptoms of vulvovaginal atrophy were randomly assigned to receive a single injection session of either cross-linked hyaluronic acid gel (n=80) or placebo gel (n=37).

Baseline characteristics were similar between the treatment groups. Overall, the mean age of the women was 59.3 years, and the mean duration of VVA symptomatology was 5.5 years. Dyspareunia was the most frequently reported MBS (63 percent). The mean MBS and FSFI full scale scores were 2.8 and 15.55, respectively.