Comment on “Hyaluronic Acid for Vaginal Health and Quality of Life in Postmenopausal Women: A Systematic Review and Meta-analysis of Randomized Controlled Trials”

Menopause is associated with both physical and psychological changes that can cause sexual discomfort, negative emotional health, and decreased overall life satisfaction. Some of the most impactful symptoms relate to vaginal health, including vulvovaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM). Hyaluronic acid (HA) has recently been promoted as a treatment option for the hydration and repair of vaginal tissue; results from previous studies have been inconsistent in methodology, outcomes, and comparison groups, and no definitive evidence exists surrounding the safety and efficacy of HA. This study was a systematic review and meta-analysis of randomized controlled trials evaluating HA versus placebo for postmenopausal vaginal symptoms.

A literature review was performed using MEDLINE (PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ClinicalTrials.gov. Inclusion criteria for studies were those focusing on postmenopausal women (with more than 12 mo of amenorrhea or surgical menopause) and those using interventions including any topical HA formulation with HA as the primary active ingredient. The primary outcomes for this study included quality of life (QoL) measures and tolerability (including adverse events and medication discontinuation). Secondary outcomes included patient reports of symptom relief according to the Vaginal Health Index (VHI) and including symptoms of vaginal dryness, dyspareunia, itching, the Vaginal Maturation Index (VMI), global impression of improvement, and sexual function through the women’s sexual function index (FSFI). Risk of bias of included studies was assessed using a validated tool for randomized trials.

The final analysis included 11 randomized controlled trials published between 2011 and 2025, including sample sizes as low as 20 and as high as 144. A total of 7 studies compared HA to active treatments, and the other 4 compared HA to placebo. Comparisons with placebo showed significant symptom relief with HA, including sexual function and vaginal health, with a favorable safety profile. Studies that compared HA to other active treatments showed it was noninferior to other treatments, with similar effectiveness and safety. This included several formulations of HA as well as varying routes and formulations of comparator medications depending on the study. All studies individually showed improvements in symptoms and QoL measures with HA, though treatment protocols varied widely and there is possible confounding in some studies from additional ingredients other than HA.

In all studies, HA was both effective and well-tolerated, and discontinuation rates were low. Pooled analysis showed significant improvement in VHI, vaginal dryness, and sexual function ( P < 0.001 for all). Overall confidence in the outcomes of the pooled analyses was low to moderate due to data heterogeneity and differences in methodology and outcome measurements.

These results indicate that HA is effective for the improvement of GSM symptoms as well as safe for patients. According to available data, HA is comparable to other available treatments and should be provided as an option by clinicians. Future research should assess differences in treatment regimens to optimize outcomes, as well as increase sample size and diversity to improve generalizability. In addition, none of the included studies in this meta-analysis reported multivariate analyses with correction for confounders, meaning that future studies should implement these controls to assess if the effect of HA remains robust after adjustment.

(Summarized from Dahab M, Ramasamy K, Ibrahim B. Hyaluronic acid for vaginal health and quality of life in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Int J Gynaecol Obstet . Published online March 3, 2026. doi:10.1002/ijgo.70887)